Utilizing systematic Mendelian randomization to identify potential therapeutic targets for mania.

Background: Mania has caused incalculable economic losses for patients, their families, and even society, but there is currently no effective treatment plan for this disease without side effects. Methods: Using bioinformatics and Mendelian randomization methods, potential drug target genes and key substances associated with mania were explored at the mRNA level. We used the chip expression profile from the GEO database to screen differential genes and used the eQTL and mania GWAS data from the IEU database for two-sample Mendelian randomization (MR) to determine core genes by colocalization. Next, we utilized bioinformatics analysis to identify key substances involved in the mechanism of action and determined related gene targets as drug targets. Results: After differential expression analysis and MR, a causal relationship between the expression of 46 genes and mania was found. Colocalization analysis yielded six core genes. Five key substances were identified via enrichment analysis, immune-related analysis, and single-gene GSVA analysis of the core genes. MR revealed phenylalanine to be the only key substance that has a unidirectional causal relationship with mania. In the end, SBNO2, PBX2, RAMP3, and QPCT, which are significantly associated with the phenylalanine metabolism pathway, were identified as drug target genes. Conclusion: SBNO2, PBX2, RAMP3, and QPCT could serve as potential target genes for mania treatment and deserve further basic and clinical research. Medicinal target genes regulate the phenylalanine metabolism pathway to achieve the treatment of mania. Phenylalanine is an important intermediate substance in the treatment of mania that is regulated by drug target genes.

Identification and validation of cortisol-related hub biomarkers and the related pathogenesis of biomarkers in Ischemic Stroke.

BACKGROUND: Ischemic stroke is a disease in which cerebral blood flow is blocked due to various reasons, leading to ischemia, hypoxia, softening, and even necrosis of brain tissues. The level of cortisol is related to the occurrence and progression of ischemic stroke. However, the mechanism governing their interrelationship is still unclear. The main objective of this study was to identify and understand the molecular mechanism between cortisol and IS. METHODS: The common cortisol-related biological processes were screened by mutual verification of two data sets and the cortisol-related hub biomarkers were identified. Modular analysis of protein interaction networks was performed, and the differential pathway analysis of individual genes was conducted by GSVA and GSEA. Drug and transcription factor regulatory networks of hub genes were excavated, and the diagnostic potential of hub genes was analyzed followed by the construction of a diagnostic model. RESULTS: By screening the two data sets by GSVA, three biological processes with common differences were obtained. After variation analysis, four cortisol-related hub biomarkers (CYP1B1, CDKN2B, MEN1, and USP8) were selected. Through the modular analysis of the protein-protein interaction network and double verification of GSVA and GSEA, a series of potential molecular mechanisms of hub genes were discovered followed by a series of drug regulatory networks and transcription factor regulatory networks. The hub biomarkers were found to have a high diagnostic value by ROC; thus, a diagnostic model with high diagnostic efficiency was constructed. The diagnostic value was mutually confirmed in the two data sets. CONCLUSION: Four cortisol-related hub biomarkers are identified in this study, which provides new ideas for the key changes of cortisol during the occurrence of IS.

Oscillatory rheometry for elucidating the influence of non-network biopolymer aggregation on pectin-gelatin composite gels.

Gel networks formed from biopolymers have intrigued rheological interest, especially in the food industry. Despite ubiquitous non-network biopolymer aggregation in real gel food systems, its fundamental rheological implications remain less understood. This study addresses this by preparing pectin-gelatin composite gels with dispersed or aggregated biopolymers and comparatively analyzing viscoelastic responses using rheometry. Subtle discrepancies in non-network biopolymer states were revealed through oscillatory shearing at different frequencies and amplitudes. Biopolymer aggregation in the network notably influenced loss tangent frequency dependency, particularly at high frequencies, elevating I3/I1 values and sensitizing the yield point. Non-network biopolymers weakened Payne effects and gel non-linearity. A combination of strain stiffening and shear thinning nonlinear responses characterized prepared gel systems. Aggregation of pectin and gelatin enhanced shear thinning, while strain stiffening was notable in highly aggregated pectin cases. This study enhances understanding of the link between non-network structural complexity and viscoelastic properties in oscillatory rheometry of food gels.

First classification of iron meteorite fragment preserved in Chang'e-5 lunar soils.

Lunar soil preserves numerous fragments of meteorites impacting on the Moon, providing a unique opportunity to investigate the distribution of the types of projectiles over billions of years. Here we report the first discovery of an iron meteorite fragment from the Chang'e-5 lunar soil, which consists mainly of martensite (quenched from taenite), kamacite, and schreibersite, with a trace of pentlandite. The meteorite fragment is Ni- and P-rich, S-poor, and based on its mineral chemistry and bulk composition, can be classified into the IID-group, a rare and carbonaceous group of iron meteorite originating in the outer Solar System. This meteorite fragment experienced only limited partial melting followed by fast cooling, suggestive of efficient preservation of intact remnants of iron meteorites impacting on the porous lunar regolith. Alternatively, it is a relic of a low-velocity impact of submillimeter-sized metal grains originated from an IID-like iron meteorite. Our observations demonstrate that it is feasible to achieve the type distribution of meteorites impacting on the Moon via systematically analyzing a large number of metal grains separated from lunar soils, thus shedding light on the dynamic evolution of the Solar System.

Efficacy of multi-slice spiral computed tomography in evaluating gastric cancer recurrence after endoscopic submucosal dissection.

BACKGROUND: Recurrence is the major challenge facing endoscopic submucosal dissection (ESD)-based treatment therapies for early gastric cancer (EGC). Urgent development of simple and easy surveillance approaches will enhance clinical treatment of the disease. AIM: To explore the role of computed tomography (CT) recurrence in evaluating EGC after ESD treatment. METHODS: We retrospectively recruited patients from our endoscopy department, between January 2002 and December 2015, and analyzed their basic characteristics, including symptoms, CT results, and results of endoscopy with biopsy, among others. RESULTS: Among a total of 2150 patients EGC patients surveyed, 1362 met our inclusion and exclusion criteria and were therefore enrolled in our study. The cohort's sensitivity of CT for recurrent GC and specificity were 44.22% and 43.86%, respectively, with negative and positive predictive values of 40.15% (275/685) and 48.01% (325/677), respectively. The area under the curve of arterial and venous CT values for recurrent EGC were 0.545, and 0.604, respectively. Receiver operating characteristic curve revealed no statistically significant differences between arterial and venous CT values for recurrent EGC. CONCLUSION: Enhanced CT has superior diagnostic efficacy, but less accuracy, compared to gold standard techniques in patients with recurrent EGC.

Synthesis of NiMoO4/NiMo@NiS Nanorods for Efficient Hydrogen Evolution Reactions in Electrocatalysts.

As traditional energy structures transition to new sources, hydrogen is receiving significant research attention owing to its potential as a clean energy source. The most significant problem with electrochemical hydrogen evolution is the need for highly efficient catalysts to drive the overpotential required to generate hydrogen gas by electrolyzing water. Experiments have shown that the addition of appropriate materials can reduce the energy required for hydrogen production by electrolysis of water and enable it to play a greater catalytic role in these evolution reactions. Therefore, more complex material compositions are required to obtain these high-performance materials. This study investigates the preparation of hydrogen production catalysts for cathodes. First, rod-like NiMoO4/NiMo is grown on NF (Nickel Foam) using a hydrothermal method. This is used as a core framework, and it provides a higher specific surface area and electron transfer channels. Next, spherical NiS is generated on the NF/NiMo4/NiMo, thus ultimately achieving efficient electrochemical hydrogen evolution. The NF/NiMo4/NiMo@NiS material exhibits a remarkably low overpotential of only 36 mV for the hydrogen evolution reaction (HER) at a current density of 10 mA·cm-2 in a potassium hydroxide solution, indicating its potential use in energy-related applications for HER processes.

In situ analysis of surface composition and meteorology at the Zhurong landing site on Mars.

The Zhurong rover of the Tianwen-1 mission landed in southern Utopia Planitia, providing a unique window into the evolutionary history of the Martian lowlands. During its first 110 sols, Zhurong investigated and categorized surface targets into igneous rocks, lithified duricrusts, cemented duricrusts, soils and sands. The lithified duricrusts, analysed by using laser-induced breakdown spectroscopy onboard Zhurong, show elevated water contents and distinct compositions from those of igneous rocks. The cemented duricrusts are likely formed via water vapor-frost cycling at the atmosphere-soil interface, as supported by the local meteorological conditions. Soils and sands contain elevated magnesium and water, attributed to both hydrated magnesium salts and adsorbed water. The compositional and meteorological evidence indicates potential Amazonian brine activities and present-day water vapor cycling at the soil-atmosphere interface. Searching for further clues to water-related activities and determining the water source by Zhurong are critical to constrain the volatile evolution history at the landing site.

Fear stress promotes glioma progression through inhibition of ferroptosis by enhancing FSP1 stability

Purpose Patients diagnosed with cancer often suffer from emotional stressors, such as anxiety, depression, and fear of death. However, whether fear stress could influence the glioma progression is still unclear. Methods Xenograft glioma animal models were established in nude mice. Tumor-bearing mice were subjected to fear stress by living closely with cats and then their depressive behaviors were measured using an open field test. Hematoxylin and eosin staining, the TUNEL staining and immunochemical staining were used to detect the histopathological changes of tumor tissues. Gene expression profiling was used to screen the aberrant gene expression. Methylated RNA immunoprecipitation was used to identify the RNA m6A level. Gene expression was measured by western blot and real-time PCR, respectively. Results We found that fear stress promoted glioma tumor progression in mice. Fear stress-induced upregulation of METTL3 and FSP1, increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells, the cells viability of glioma significantly was decreased and ferroptosis was enhanced in glioma cells. Conclusions Fear stress-induced upregulation of METTL3 stabilized FSP1 mRNA by m6A modification, leading to tumor progression through inhibition of ferroptosis. Our study provides a new understanding of psychological effects on glioma development, and new insights for glioma therapy (AU)

Reactive Hydrogel Patch for SERS Detection of Environmental Formaldehyde.

The tobacco epidemic is a public health threat that has taken a heavy toll of lives around the globe each year. As one of the poison species from smoking, formaldehyde (FA) affects both the smokers and nearby persons who are exposed to second-hand smoke. Therefore, on-site tracking of FA exposure could evaluate the public environmental safety and mitigate the potential hazards. Herein, we first prepare SiO2-shelled AuAg alloy nanoparticles (AuAg@SiO2) and then embed AuAg@SiO2 within agarose hydrogel to construct the three-dimensional (3D) surface-enhanced Raman scattering (SERS) substrate. A reagent of 3-methyl-2-benzothiazolinone hydrazine (MBTH) with reaction activity toward FA is loaded in the 3D substrate to obtain the selective SERS patch (designated as M-hydrogel patch). Based on a marker Raman peak at 1273 cm-1 from the reaction product of MBTH-FA, the M-hydrogel patch is used to realize SERS detection of FA in smoke. A good linear relationship from 5 × 10-4 to 5 mg/m3 and a limit of detection (LOD) of 2.92 × 10-5 mg/m3 could be reached. While for detection of FA in aqueous, a linear range of 1 × 10-7-1 × 10-3 mg/mL with an LOD of 1.46 × 10-8 mg/mL could be achieved. As the real application, the proposed M-hydrogel patch could be placed anywhere indoor to SERS evaluate the spatial distribution of FA in tobacco smoke, which is in connection with the second-hand smoke effect on children and adults. Such M-hydrogel patch-based SERS assay is exerted for on-field detection of FA in water and furniture panels by using a portable Raman system, showing satisfactory selectivity and reproducibility.

NanoSIMS sulfur isotopic analysis at 100 nm scale by imaging technique.

NanoSIMS has been widely used for in-situ sulfur isotopic analysis (32S and 34S) of micron-sized grains or complex zoning in sulfide in terrestrial and extraterrestrial samples. However, the conventional spot mode analysis is restricted by depth effects at the spatial resolution < 0.5-1 µm. Thus sufficient signal amount cannot be achieved due to limited analytical depths, resulting in low analytical precision (1.5‰). Here we report a new method that simultaneously improves spatial resolution and precision of sulfur isotopic analysis based on the NanoSIMS imaging mode. This method uses a long acquisition time (e.g., 3 h) for each analytical area to obtain sufficient signal amount, rastered with the Cs+ primary beam of ∼100 nm in diameter. Due to the high acquisition time, primary ion beam (FCP) intensity drifting and quasi-simultaneous arrival (QSA) significantly affects the sulfur isotopic measurement of secondary ion images. Therefore, the interpolation correction was used to eliminate the effect of FCP intensity variation, and the coefficients for the QSA correction were determined with sulfide isotopic standards. Then, the sulfur isotopic composition was acquired by the segmentation and calculation of the calibrated isotopic images. The optimal spatial resolution of ∼ 100 nm (Sampling volume of 5 nm × 1.5 µm2) for sulfur isotopic analysis can be implemented with an analytical precision of ∼1‰ (1SD). Our study demonstrates that imaging analysis is superior to spot-mode analysis in irregular analytical areas where relatively high spatial resolution and precision are required and may be widely applied to other isotopic analyses.

Study on an Animal Model of Seawater Immersion Injury Following Hemorrhagic Shock.

INTRODUCTION: To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS). METHODS: Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded. RESULTS: After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05. CONCLUSIONS: The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock.

Design, synthesis and structure-activity relationship of N-phenyl aromatic amide derivatives as novel xanthine oxidase inhibitors.

Our previous studies suggested that N-phenyl aromatic amides are a class of promising xanthine oxidase (XO) inhibitor chemotypes. In this effort, several series of N-phenyl aromatic amide derivatives (4a-h, 5-9, 12i-w, 13n, 13o, 13r, 13s, 13t and 13u) were designed and synthesized to carry out an extensive structure-activity relationship (SAR). The investigation provided some valuable SAR information and identified N-(3-(1H-imidazol-1-yl)-4-((2-methylbenzyl)oxy)phenyl)-1H-imidazole-4-carboxamide (12r, IC50 = 0.028 µM) as the most potent XO inhibitor with close in vitro potency to that of topiroxostat (IC50 = 0.017 µM). Molecular docking and molecular dynamics simulation rationalized the binding affinity through a series of strong interactions with the residues Glu1261, Asn768, Thr1010, Arg880, Glu802, etc. In vivo hypouricemic studies also suggested that the uric acid lowering effect of compound 12r was improved compared with the lead g25 (30.61 % vs 22.4 % reduction in uric acid levels at 1 h; 25.91 % vs 21.7 % reduction in AUC of uric acid) . Pharmacokinetic studies revealed that compound 12r presented a short t1/2 of 0.25 h after oral administration. In addition, 12r has non-cytotoxicity against normal cell HK-2. This work may provide some insights for further development of novel amide-based XO inhibitors.

Fear stress promotes glioma progression through inhibition of ferroptosis by enhancing FSP1 stability.

PURPOSE: Patients diagnosed with cancer often suffer from emotional stressors, such as anxiety, depression, and fear of death. However, whether fear stress could influence the glioma progression is still unclear. METHODS: Xenograft glioma animal models were established in nude mice. Tumor-bearing mice were subjected to fear stress by living closely with cats and then their depressive behaviors were measured using an open field test. Hematoxylin and eosin staining, the TUNEL staining and immunochemical staining were used to detect the histopathological changes of tumor tissues. Gene expression profiling was used to screen the aberrant gene expression. Methylated RNA immunoprecipitation was used to identify the RNA m6A level. Gene expression was measured by western blot and real-time PCR, respectively. RESULTS: We found that fear stress promoted glioma tumor progression in mice. Fear stress-induced upregulation of METTL3 and FSP1, increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells, the cells viability of glioma significantly was decreased and ferroptosis was enhanced in glioma cells. CONCLUSIONS: Fear stress-induced upregulation of METTL3 stabilized FSP1 mRNA by m6A modification, leading to tumor progression through inhibition of ferroptosis. Our study provides a new understanding of psychological effects on glioma development, and new insights for glioma therapy.

MnO2 coated Au nanoparticles advance SERS detection of cellular glutathione.

Glutathione, referred to as GSH, abnormal physiologic level of GSH is an indication to some neurodegenerative diseases and cancers. A measurement of cellular GSH calls for rapid, sensitive, and selective methods. In this work, we rationally design and prepare Au@MnO2 core-shell composite nanoparticles combining with tetramethylbenzidine (TMB) molecules to determine intracellular GSH by Surface enhanced Raman scattering (SERS) technique. MnO2 plays multifunctional roles in the method, including the participation in catalyzing TMB to molecules form dimer charge-transfer complex (CTC) which own a great SERS signal reporter. With the addition of GSH, the MnO2 will be dissolving detaching CTC molecules from the surface of Au@MnO2 and resulting in a signal-off off SERS response and indirect and sensitive detection of GSH could be realized. The limit of detection of GSH by SERS method is as low as 0.1 µmol/L and a good linear relationship of GSH is found in the range from 0.5 to 30 µmol/L. Au@MnO2-SERS assay is successfully applied to detect cellular GSH, which is validated by using Enzyme-linked-immunoassay-based Kit. The Au@MnO2-SERS protocol has promising potential for clinical application.

The polychloromethylation/acyloxylation of 1,6-enynes with chloroalkanes and diacyl peroxides through dual-role designs.

The novel polychloromethylation/acyloxylation of 1,6-enynes with chloroalkanes and diacyl peroxides through dual-role designs has been developed to prepare 2-pyrrolidinone derivatives with polychloromethyl units with the use of an inexpensive copper salt under mild conditions. This strategy includes two dual-role designs, not only improving atomic utilization but also allowing a cleaner process. The wide substrate scope and simple reaction conditions demonstrate the practicability of this protocol.

Cyclization/hydrolysis of 1,5-enenitriles initiated by sulfonyl radicals in the aqueous phase in the presence of the I2/TBHP system.

A novel cyclization/hydrolysis of 1,5-enenitriles for the synthesis of valuable pyrrolidine-2,4-diones in the aqueous phase using I2 as the catalyst and tert-butyl hydroperoxide (TBHP) as the oxidant is reported. In the presence of the I2/TBHP system, sulfonyl hydrazides produce sulfonyl radicals, which undergo radical addition, intramolecular cyclization, hydrogen abstraction, and hydrolysis to give the final products. The use of the inexpensive and environmentally friendly I2/TBHP catalytic oxidation system in the aqueous phase makes it a benign and sustainable strategy.

SERS determination of dopamine using metal-organic frameworks decorated with Ag/Au noble metal nanoparticle composite after azo derivatization with p-aminothiophenol.

A specific surface-enhanced Raman scattering (SERS) assay for dopamine (DA) based on an azo derivatization reaction is proposed for the first time by preparation of p-aminothiophenol (PATP)-modified composite SERS substrate, composed of metal-organic framework (MIL-101) decorated with Au and Ag nanoparticles. As the result, the SERS method for detection of the azo reaction between PATP and DA exhibits superior sensitivity, selectivity, and stability. A reasonable linearity in the range 10-6 to 10-10 mol∙L-1 is achieved, and the limit of detection is 1.2 × 10-12 mol∙L-1. The reactive SERS assay is free from interference in complex physiological fluid. The feasibility of the proposed SERS method for the detection of DA levels in fetal bovine serum (FBS) samples and human serum samples is validated by HPLC-MS methods, displaying promising application potential in early disease diagnosis.

Visual Health Analysis of Print Advertising Graphic Design Based on Image Segmentation and Few-Shot Learning.

Graphics innovation must adapt to the changing trends of the times in order to stay ahead of the curve. This article investigates the use of graphic vision in print advertising design, using image segmentation as a starting point and examines the current state of visual innovation in print advertising graphic design and its various expressions and applications. A series of homogeneous regions are generated and outlined using an image segmentation algorithm based on adaptive local threshold. The user then paints different colors on the area sets that make up the various targets. Finally, the image segmentation is completed by merging the color mark region sets. Automatic extraction of the initial curve of an active contour model, construction of an active contour model based on saliency and level set solution, automatic selection of training samples when a classifier is used for image segmentation, and so on are all problems that this method effectively solves. Experiments show that this algorithm not only satisfies users' demands for more intuitive input and more accurate interactive image segmentation results but also enables multiregion and multitarget image segmentation with ease.

In situ detection of water on the Moon by the Chang'E-5 lander.

We report analysis results of the reflectance spectra (0.48 to 3.2 µm) acquired by the Chang'E-5 lander, which provides vital context of the returned samples from the Northern Oceanus Procellarum of the Moon. We estimate up to 120 parts per million (ppm) of water (OH + H2O) in the lunar regolith, which is mostly attributed to solar wind implantation. A light-colored and surface-pitted rock (named as CE5-Rock) is evident near the lander. The reflectance spectra suggest that CE5-Rock could be transported from an older basalt unit. CE5-Rock exhibits a stronger absorption, near 2.85 µm, than the surrounding regolith, with estimation of ~180 ppm of water if the model for estimating water content of regolith is applicable to rock samples, which may suggest an additional source from the lunar interior. The low water content of the regolith may suggest the degassing of mantle reservoir beneath the Chang'E-5 landing site.

Discovery of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives as novel xanthine oxidase inhibitors.

A series of 4-(phenoxymethyl)-1H-1,2,3-triazole derivatives were designed, synthesized, and evaluated for their xanthine oxidase (XO) inhibitory activities. Among these compounds, 9m emerged as the most effective XO inhibitor with an IC50 value of 0.70 µM, which was approximately 14-fold more potent than allopurinol. Additionally, compound 9m displayed favorable drug-like properties with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.33 and 3.41, respectively. We further explored the binding mode of 9m in complex with XO by molecular docking and molecular dynamics studies. In vivo hypouricemic studies also suggested that 9m could effectively lower the serum uric acid levels of rat. In summary, compound 9m could be a promising lead for further development of XO inhibitors.