The complex roles of m 6 A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases.

N6-methyladenosine (m 6 A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m 6 A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m 6 A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m 6 A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m 6 A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m 6 A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m 6 A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m 6 A's role in neurodegenerative processes. The roles of m 6 A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the time-specific nature of m 6 A and its varying effects on distinct brain regions and in different environments.

Cyclic Continuous Glycation Enhanced Dispersibility of Myofibrillar Protein: Reaction Efficiency and Sites Modification.

Reaction efficiency in glycation lacks sufficient attention, leading to the waste of process costs. Cyclic continuous glycation (CCG) is an effective approach to accelerate covalent binding between myofibrillar protein (MP) and glucose. This study elucidated that CCG promoted the exposure of reactive glycated sites in MP with full unfolding of secondary and tertiary structures. Notably, the glycation rate was significantly increased by 65.43%. Physicochemical properties indicated that MP-glucose conjugates with high graft degree exhibited favorable solubility, dispersibility, and thermal stability. Furthermore, proteomics was applied to reveal the glycated sites and products in glycoconjugates of MP. Glycation preferentially acted on the tails of the myosin heavy chain. The glucosylation modification on the head region was enhanced by CCG contributing to the inhibition of the head-head interaction. Overall, this study systematically clarifies the mechanism of CCG, providing a theoretical basis for the application of glycation in innovative meat products.

A lysosome-targeting rhodamine fluorescent probe for Cu2+ detection and its applications in test kits and zebrafish imaging.

Tracing copper ions levels in the environment and subcellular microenvironment is crucial due to the key role copper ions play in physiological and pathological processes. Herein, a novel naphthalimide-fused rhodamine probe Rh-Naph-Cu was prepared through modification with phenylhydrazine to produce a closed and non-fluorescent spirolactam. Based on the copper-induced spirolactam ring-opening and hydrolysis process, Rh-Naph-Cu can be employed as a fluorescence off-on probe for copper ions with high selectivity, high sensitivity (limit of detection: 33.0 nM), broad pH-response range (pH: 5.0-10.0), and color change visible with the naked eye. Rh-Nap-Cu could be made into test strips for the in-situ chromogenic detection of Cu2+. Significantly, Rh-Naph-Cu can be utilized for the detection of copper ions in living HeLa cells and zebrafish, and exhibits excellent lysosomal-targeting ability with high Pearson's correlation coefficient (PCC) of 0.96.

Characteristics of anti-contactin1 antibody positive autoimmune nodopathies combined with membranous nephropathy.

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

Bioinformatics Identification and Expression Analysis of Acetyl-CoA Carboxylase Reveal Its Role in Isoflavone Accumulation during Soybean Seed Development.

Isoflavones belong to the class of flavonoid compounds, which are important secondary metabolites that play a crucial role in plant development and defense. Acetyl-CoA carboxylase (ACCase) is a biotin-dependent enzyme that catalyzes the conversion of Acetyl-CoA into Malonyl-CoA in plants. It is a key enzyme in fatty acid synthesis and also catalyzes the production of various secondary metabolites. However, information on the ACC gene family in the soybean (Glycine max L. Merr.) genome and the specific members involved in isoflavone biosynthesis is still lacking. In this study, we identified 20 ACC family genes (GmACCs) from the soybean genome and further characterized their evolutionary relationships and expression patterns. Phylogenetic analysis showed that the GmACCs could be divided into five groups, and the gene structures within the same groups were highly conserved, indicating that they had similar functions. The GmACCs were randomly distributed across 12 chromosomes, and collinearity analysis suggested that many GmACCs originated from tandem and segmental duplications, with these genes being under purifying selection. In addition, gene expression pattern analysis indicated that there was functional divergence among GmACCs in different tissues. The GmACCs reached their peak expression levels during the early or middle stages of seed development. Based on the transcriptome and isoflavone content data, a weighted gene co-expression network was constructed, and three candidate genes (Glyma.06G105900, Glyma.13G363500, and Glyma.13G057400) that may positively regulate isoflavone content were identified. These results provide valuable information for the further functional characterization and application of GmACCs in isoflavone biosynthesis in soybean.

Flexible control and trajectory planning of medical two-arm surgical robot.

This paper introduces the flexible control and trajectory planning medical two-arm surgical robots, and employs effective collision detection methods to ensure the safety and precision during tasks. Firstly, the DH method is employed to establish relative rotation matrices between coordinate systems, determining the relative relationships of each joint link. A neural network based on a multilayer perceptron is proposed to solve FKP problem in real time. Secondly, a universal interpolator based on Non-Uniform Rational B-Splines (NURBS) is developed, capable of handling any geometric shape to ensure smooth and flexible motion trajectories. Finally, we developed a generalized momentum observer to detect external collisions, eliminating the need for external sensors and thereby reducing mechanical complexity and cost. The experiments verify the effectiveness of the kinematics solution and trajectory planning, demonstrating that the improved momentum torque observer can significantly reduce system overshoot, enabling the two-arm surgical robot to perform precise and safe surgical tasks under algorithmic guidance.

Development of low-toxicity antimicrobial polycarbonates bearing lysine residues.

Antibiotic resistance has been threatening public health for a long period, while the COVID pandemic aggravated the scenario. To combat antibiotic resistance strains, host defense peptides (HDPs) mimicking molecules have attracted considerable attention. Herein, we reported a series of polycarbonates bearing cationic lysine amino acid residues that could mimic the mechanism of action of HDPs and possess broad-spectrum antimicrobial activity. Moreover, those polymers had negligible toxicity toward red blood cells and mammalian cells. The membrane-disruption mechanism endows the lysine-containing polycarbonates with low possibility of resistance development and the fast killing kinetics, making them promising candidates for antimicrobial development.

Positive Intervention of Distinct Peptides in Clostridioides difficile Infection in a Mouse Model.

Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure. Overall, E. japonicus peptides showed better results than G. max peptides in treating CDI. This study supports the potential treatment of CDI with natural peptides and promotes the development of specialty foods for CDI enteritis. Clostridioides difficile infection (CDI) is a common healthcare-associated infection and the leading cause of gastroenteritis-related deaths worldwide. To investigate the effects of peptide composition of different protein products on CDI, we analyzed and compared the peptide sequences and compositions from Engraulis japonicus and Glycine max using Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). An animal model of CDI was also established to investigate the potential therapeutic effects of these peptides in vivo. The peptide compositions of E. japonicus and G. max differed, with only 11% of the peptide sequences being identical. Oral administration of the tested peptides could reduce intestinal inflammation, repair the intestinal barrier, increase the proportion of beneficial bacteria, and reduce the proportion of harmful bacteria, providing a therapeutic effect against CDI. However, the peptides may differ considerably in some aspects. E. japonicus peptides were superior to G. max peptides in promoting colon epithelial cell proliferation and repairing tight intestinal cell junctions. Interestingly, the two sources of peptides have different effects on the cecal microbiome. E. japonicus peptides can effectively restore the diversity and richness of intestinal microbiota, while G. max peptides have poor regulatory effects on the intestinal microbiota structure.

Prevalence and risk factors of long COVID among maintenance hemodialysis patients post SARS-CoV-2 infection: A one-year follow-up study in China.

Patients undergoing maintenance hemodialysis (MHD) are a high-risk group susceptible to SARS-CoV-2 infection and long-COVID syndrome appearance. However, there is limited and unclear evidence for long COVID in MHD patients. We collected the general information, symptoms, signs and laboratory indices of 366 MHD patients infected with COVID-19 and conducted 12 months follow-up with a series of questionnaires. As a result, 285 MHD patients had long COVID, with the most common symptoms were fatigue (84.69%) and muscle weakness (72.45%). Mobility problem (p < 0.001), anxiety/depression (p = 0.002) and breathlessness (p < 0.001) were more prevalent in long COVID patients than in non-long COVID patients. Persistent long COVID people were more likely to report all domains problems of the EQ-5D-5L. Age, female, inadequate dialysis (Kt/V < 1.2), coagulation abnormalities (d-dimer > 1 mg/L) and more comorbidities were risk factors for the development of long COVID. In addition to these factors, elevated inflammatory markers (CRP > 10 mg/L) represent an extra risk factor for the persistence of long COVID symptoms in MHD patients. And more than 80% of long COVID symptoms would resolve after 1 year in MHD patients, of which the sixth month after COVID-19 infection is a critical turning point. In conclusion, more than 68% of MHD patients have long COVID, which has a poor impact on their health status and quality of life. These risk factors for the development and persistence of long COVID deserve the attention of clinicians.

Pestiorosins A-F, New Papulacandins Isolated from the Fungus Pestalotiopsis rosea YNJ21.

Six previously unreported papulacandins, namely pestiorosins A-F (1-6), were isolated from the fermentation products of the fungus Pestalotiopsis rosea YNJ21 isolated from the fruitbody of Amanita exitialis. The structures of these compounds, along with a known compound called pestiocandin (7), were determined using MS, NMR data, and modified Mosher's method. All compounds exhibited significant antifungal activity against Candida albicans, with MIC values ranging from 0.06 to 2.00 µg/mL. In terms of cytotoxicity assays, compounds 3 and 6 demonstrated moderate inhibitory activity against human breast cancer MCF-7 cells with IC50 values of 24.50 and 16.83 µM, respectively. On the other hand, compound 7 displayed similar levels of inhibitory activity against mice microglial BV2 cells with an IC50 value of 24.51 µM.

Factors associated with stigma in patients undergoing hemodialysis: a meta-analysis and systematic review.

BACKGROUND: Patients with hemodialysis (HD) frequently encounter stigma, which impacts their social network and adherence to treatment, increasing their risk of depression and lowering their quality of life. The factors associated with stigma among patients with HD remain poorly understood due to insufficient evidence. To fill this gap, this meta-analysis was conducted. METHODS: We carried out a thorough literature review in both Chinese and English databases like China National Knowledge Infrastructure (CNKI), Wan Fang Knowledge Data Service Platform, PubMed, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Web of Science. We included literature up to May 25, 2024, focusing on the levels and factors related to stigma in HD patients. Data extraction and quality assessment of the included literature were separately carried out by two researchers, who also independently did the literature screening. Data analysis was carried out using Stata 15.1 software. The possible sources of heterogeneity were explored by sensitivity analysis and subgroup analysis, and the robustness of the results was evaluated. RESULTS: A total of 12 papers were included, and the quality of these papers was evaluated as moderate or above. The findings of the meta-analysis demonstrated that the pooled stigma mean score was 59.30 [95% (Confidence interval) CI: 55.62 to 62.97]. Per capita monthly family income [MD (Mean Deviation) =4.95, 95% CI (1.55 to 8.35), P=0.004], residence [MD=-4.66, 95% CI (-6.96 to -2.36), P<0.001], complications [MD=4.76, 95% CI (0.92 to 8.61), P=0.015], family function [Z=-0.29, 95% CI (-0.38 to -0.21), P<0.001], self-efficacy [Z=-0.37, 95% CI (-0.48 to -0.26), P<0.001], levels of social support [Z=-0.35, 95% CI (-0.45 to -0.25), P<0.001], and levels of psychological distress [Z=0.59, 95% CI (0.26 to 0.91), P<0.001] were all significant factors contributing to stigma in patients undergoing HD. CONCLUSION: Healthcare professionals should pay attention to the early assessment of stigma in patients with HD, implement personalized interventions targeting related factors, and promote effective coping strategies for managing the disease.

Magnesium-Mediated Cross-Electrophile Couplings of Aryl 2-Pyridyl Esters with Aryl Bromides for Ketone Synthesis through In Situ-Formed Arylmagnesium Intermediates.

Aryl 2-pyridyl esters could efficiently undergo cross-electrophile couplings with aryl bromides with the aid of magnesium as a reducing metal in the absence of a transition-metal catalyst, leading to the unsymmetrical diaryl ketones in modest to good yields with wide functionality compatibility. In addition, the reaction could be easily scaled up and applied in the late-stage modification of biologically active molecules. Preliminary mechanistic study showed that the coupling reaction presumably proceeds through the in situ formation of arylmagnesium reagents as key intermediates.

Targeted sulfur(VI) fluoride exchange-mediated covalent modification of a tyrosine residue in the catalytic pocket of tyrosyl-DNA phosphodiesterase 1.

Developing effective inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) has been challenging because of the enzyme shallow catalytic pocket and non-specific substrate binding interactions. Recently, we discovered a quinolone-binding hot spot in TDP1's active site proximal to the evolutionary conserved Y204 and F259 residues that position DNA. Sulfur (VI) fluoride exchange (SuFEx) is a biocompatible click chemistry reaction that enables acylation of protein residues, including tyrosine. Selective protein modifications can provide insights into the biological roles of proteins and inform ligand design. As we report herein, we used SuFEx chemistries to prepare covalent TDP1-bound binders showing site-specific covalent bonds with Y204. Our work presents the first application of SuFEx chemistries to TDP1 ligands. It validates the ability to covalently modify specific TDP1 residues by designed targeting and adds to the chemical biology resource toolbox for studying TDP1.

Economic analysis of hydrogen energy systems: A global perspective.

In the realm of renewable energy, the integration of wind power and hydrogen energy systems represents a promising avenue towards environmental sustainability. However, the development of cost-effective hydrogen energy storage solutions is crucial to fully realize the potential of hydrogen as a renewable energy source. By combining wind power generation with hydrogen storage, a comprehensive hydrogen energy system can be established. This study aims to devise a physiologically inspired optimization approach for designing a standalone wind power producer that incorporates a hydrogen energy system on a global scale. The optimization process considers both total cost and capacity loss to determine the optimal configuration for the system. The optimal setup for an off-grid solution involves the utilization of eight distinct types of compact horizontal-axis wind turbines. Additionally, a sensitivity analysis is conducted by varying component capital costs to assess their impact on overall cost and load loss. Simulation results indicate that at a 15 % loss, the cost of energy (COE) is $1.3772, while at 0 % loss, it stands at $1.6908. Capital expenses associated with wind turbines and hydrogen storage systems significantly contribute to the overall cost. Consequently, the wind turbine-hydrogen storage system emerges as the most cost-effective and reliable option due to its low cost of energy.

Whole-genome analysis of circulating influenza A virus (H3N2) strains in Shanghai, China from 2005 to 2023.

Seasonal influenza A virus subtype H3N2 (A/H3N2) circulates globally and has been linked to higher hospitalization rates and summer outbreaks in temperate regions. Here, A/H3N2 circulation in Shanghai, China was systematically studied using data and materials generated by the Shanghai influenza surveillance network from 2005 to 2023. Time-series analysis of incidence and subtyping data showed that A/H3N2 co-circulated with other (sub)types and dominated in multiple seasonal influenza peaks, preferentially in summer. Whole genomes of 528 representative strains were sequenced, and spatiotemporal phylodynamic analysis using these and GISAID-archived sequences demonstrated that in the years before the COVID-19 pandemic, phylogenetically similar strains were circulating locally and elsewhere. However, clade 1a.1 (within 3C.2a.1b.2a), circulated in and only in Shanghai and domestically in 2022, while the sibling clade 2 predominated in other regions. Interestingly, clade 1a.1 was swiftly and completely replaced by clade 2, mostly 2a.3a.1, at the start of 2023. In hemagglutination inhibition and neutralization assays, sera from healthy donors collected in 2022 displayed higher or similar reactivity against 2a.3a.1 compared to 1a.1. By contrast, transcription and replication competence of 2a.3a.1 in MDCK cells was higher than 1a.1. These results indicated that instead of antigenicity differences enabling evasion of pre-existing immunity, higher replicative capability more likely contributed to 2a.3a.1 viruses achieving dominance in China. In addition to summarizing patterns of A/H3N2 local circulation in Shanghai, this work revealed an unusual episode in A/H3N2 global circulation and evolution dynamics in connection to the COVID-19 pandemic and explored possible mechanistic explanations.

Effects of compound emulsifiers on the characteristics and stability of nano-emulsions from pollock bones.

To improve the stability of pollock bone broth, compound emulsifiers were employed and evaluated in nano-emulsions from pollock bones (PBNs). The microstructure, creaming index, particle size, zeta potential, and viscosity of PBNs were characterized and the stability of PBNs was investigated. It revealed that the concentration of compound emulsifiers is one of the principal factors for particle size, zeta potential, and viscosity of PBNs, and 0.9% of sodium caseinate and sucrose fatty acid ester (CS-SE) can make the PBN display good stability. Its particle size changed from 81.17 ± 1.33 nm to 19.62 ± 0.21 nm when the temperature ranged from 40 °C to 80 °C, and its creaming index could reach a maximum (90.83%) among all PBNs in 4 months of freeze-thaw assays. PBN stability could be improved by the compound emulsifier (CS-SE), which offers a theoretical basis for the application of pollock bone broth.

Lathyrane diterpenoids with multidrug resistance reversal activity from the tubers of Euphorbia antiquorum.

Nine previously unreported lathyrane diterpenoids named euphorantesters A-I, along with 16 known analogues, have been separated from the tubers of Euphorbia antiquorum. Their structures were established by means of spectroscopic analyses, time-dependent density functional theory based electronic circular dichroism calculation and single crystal X-ray crystallography. Their reversal ability against P-glycoprotein-mediated multidrug resistance (MDR) in MCF-7/ADR cell line was then evaluated, and 15 ones exhibited moderate MDR reversal activity with reversal fold falling in the range of 1.12-13.15. The most active euphorantester B could effectively increase the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil.

Surface crystallized supramolecular to achieve highly dispersed ultrafine nano-palladium in-situ deposition to promote thermal/electrocatalytic reduction.

To promote the greening and economization of industrial production, the development of advanced catalyst manufacturing technology with high activity and low cost is an indispensable part. In this study, nitrogen-doped hollow carbon spheres (NHCSs) were used as anchors to construct a supramolecular coating formed by the self-assembly of boron clusters and ß-cyclodextrin by surface crystallization strategy, with the help of the weak reducing agent characteristics of boron clusters, highly dispersed ultra-small nano-palladium particles were in-situ embedded on the surface of NHCSs. The deoxygenation hydrogenation of nitroaromatics and the reduction of nitrate to ammonia were used as the representatives of thermal catalytic reduction and electrocatalytic reduction respectively. The excellent properties of the constructed Pd/NHCSs were proved by the probe reaction. In the catalytic hydrogenation of nitroaromatics to aminoaromatics, the reaction kinetic rate and activation energy are at the leading level. At the same time, the constructed Pd/NHCSs can also electrocatalytically reduce nitrate to high value-added ammonia with high activity and selectivity, and the behavior of Pd/NHCSs high selectivity driving nitrate conversion was revealed by density functional theory and in situ attenuated total reflection Fourier transform infrared (ATRFTIR) technique. These results all reflect the feasibility and superiority of in-situ anchoring ultra-small nano-metals as catalysts by surface crystallization to build a supramolecular cladding with reducing properties, which is an effective way to construct high-activity and low-cost advanced catalysts.

Molecular Engineering of Porous Fe-N-C Catalyst with Sulfur Incorporation for Boosting CO2 Reduction and Zn-CO2 Battery.

Transition metal-nitrogen-carbon (M-N-C) catalysts have emerged as promising candidates for electrocatalytic CO2 reduction reaction (CO2RR) due to their uniform active sites and high atomic utilization rate. However, poor efficiency at low overpotentials and unclear reaction mechanisms limit the application of M-N-C catalysts. In this study, Fe-N-C catalysts are developed by incorporating S atoms onto ordered hierarchical porous carbon substrates with a molecular iron thiophenoporphyrin. The well-prepared FeSNC catalyst exhibits superior CO2RR activity and stability, attributes to an optimized electronic environment, and enhances the adsorption of reaction intermediates. It displays the highest CO selectivity of 94.0% at -0.58 V (versus the reversible hydrogen electrode (RHE)) and achieves the highest partial current density of 13.64 mA cm-2 at -0.88 V. Furthermore, when employed as the cathode in a Zn-CO2 battery, FeSNC achieves a high-power density of 1.19 mW cm-2 and stable charge-discharge cycles. Density functional theory calculations demonstrate that the incorporation of S atoms into the hierarchical porous carbon substrate led to the iron center becoming more electron-rich, consequently improving the adsorption of the crucial reaction intermediate *COOH. This study underscores the significance of hierarchical porous structures and heteroatom doping for advancing electrocatalytic CO2RR and energy storage technologies.