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.

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.

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.

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.

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.

Stem to prevent periprosthetic fracture after notching in total knee arthroplasty.

Improper osteotomy during total knee arthroplasty (TKA) can lead to anterior femoral notching, which increases the risk of periprosthetic fractures due to stress concentration. One potential solution is the addition of an intramedullary stem to the femoral component. However, the optimal stem length remains unclear. In this study, we aimed to determine the optimal stem length using finite element models. Finite element models of femurs were developed with unstemmed prostheses and prostheses with stem lengths of 50, 75, and 100 mm. Under squat loading conditions, the von Mises stress at the notch and stress distribution on four transversal sections of the femur were analyzed. Additionally, micromotion of the prosthesis-bone interface was evaluated to assess initial stability. The unstemmed prosthesis exhibited a von Mises stress of 191.8 MPa at the notch, which decreased to 43.1, 8.8, and 23.5 MPa for stem lengths of 50, 75, and 100 mm, respectively. The stress reduction on four selected femoral transversal sections compared with the unstemmed prosthesis was 40.0%, 84.4%, and 67.1% for stem lengths of 50, 75, and 100 mm, respectively. Micromotion analysis showed a maximum of 118.8 µm for the unstemmed prosthesis, which decreased significantly with the application of stems, particularly at the anterior flange. Intramedullary stems effectively reduced stress concentration at the femoral notch. The 50-mm stem length provided the optimal combination of reduced notch stress, minimized stress-shielding effect, and decreased micromotion at the anterior flange.

The economics of home energy usage: Insights from urban economy.

Recent regional investigations in the United States have revealed a thought-provoking perspective: household electricity consumption may act as an inferior commodity, displaying a negative correlation with wealth. This finding challenges the outcomes of various other econometric analyses and underscores the importance of scrutinizing power consumption patterns across different regional service areas. While it is commonly believed that home electricity usage decreases as income rises, this may not always hold true universally. This study focuses on power usage in Seattle, Washington households, a prominent urban economy in the Pacific Northwest. Employing dynamic error correction modeling techniques, the research demonstrates statistically significant fluctuations in domestic power usage attributed to variations in actual value, actual revenue, and cold weather. In the immediate future, energy for homes in this urban economy resembles any other commodity. However, investing in electricity for homes in Seattle may not be advisable in the long run. Home power usage in Seattle declines with each percentage point increase in actual per capita income over 1.2 %. This finding highlights the need for careful consideration and strategic planning in energy management policies for urban economies like Seattle.

Promoting CO2 Electroreduction to Hydrocarbon Products via Sulfur-Enhanced Proton Feeding in Atomically Precise Thiolate-Protected Cu Clusters.

Thiolate-protected Cu clusters with well-defined structures and stable low-coordinated Cu+ species exhibit remarkable potential for the CO2RR and are ideal model catalysts for establishing structure-electrocatalytic property relationships at the atomic level. However, extant Cu clusters employed in the CO2RR predominantly yield 2e- products. Herein, two model Cu4(MMI)4 and Cu8(MMI)4(tBuS)4 clusters (MMI = 2-mercapto-1-methylimidazole) are prepared to investigate the synergistic effect of Cu+ and adjacent S sites on the CO2RR. Cu4(MMI)4 can reduce CO2 to deep-reduced products with a 91.0% Faradaic efficiency (including 53.7% for CH4) while maintaining remarkable stability. Conversely, Cu8(MMI)4(tBuS)4 shows a remarkable preference for C2+ products, achieving a maximum FE of 58.5% with a C2+ current density of 152.1 mA∙cm-2. In situ XAS and ex situ XPS spectra reveal the preservation of Cu+ species in Cu clusters during CO2RR, extensively enhancing the adsorption capacity of *CO intermediates. Moreover, kinetic analysis and theoretical calculations confirm that S sites facilitate H2O dissociation into *H species, which directly participate in the protonation process on adjacent Cu sites for the protonation of *CO to *CHO. This study highlights the important role of Cu-S dual sites in Cu clusters and provides mechanistic insights into the CO2RR pathway at the atomic level.

Efficient Recovery of Rare Earth Elements from Acidic Wastewater by a Green ß-CDs-Functionalized Nanosponge.

The recovery of rare earth elements (REEs) from acidic wastewater is crucial to sustainable development, industrial processes, and human health. In this research, ß-cyclodextrin-based nanosponges (ß-CD/PVA-SA NSs) have been proposed as potential adsorbents for europium (Eu), dysprosium (Dy), and gadolinium (Gd) recovery. The nanosponges are synthesized by cross-linking ß-cyclodextrin (ß-CD) functionalized polyvinyl alcohol (PVA) and sodium alginate (SA). Experimental results indicate that ß-CD/PVA-SA NSs exhibit favorable selectivity for Eu, Dy, and Gd, with the maximum adsorption capacity of 222, 217, and 204 mg/g, respectively, in addition to stability and cyclicity. ß-CD/PVA-SA NSs maintain selective adsorption effects towards RE ions that are present in acidic mine drainage (AMD), thereby highlighting their potential for practical applications. Furthermore, density functional theory (DFT) simulations have unveiled the fundamental interactions between the functional groups anchored in ß-CD/PVA-SA NSs and the REEs, providing vital insights into their adsorption mechanism. Hence, the utilization of ß-CD/PVA-SA NSs has the potential to advance initiatives in remediating acidic water pollution and facilitating the sustainable recycling of RE resources.

Correlation between thyroid hormone sensitivity and diabetic peripheral neuropathy in euthyroid patients with type 2 diabetes mellitus.

Previous studies have revealed that thyroid hormone (TH) levels are associated with the risk of diabetic peripheral neuropathy (DPN) in euthyroid patients with type 2 diabetes mellitus (T2DM). However, the relationship between TH sensitivity, a complementary method for assessing thyroid function, and DPN remains unclear. This study aimed to investigate the correlation between DPN and TH sensitivity in euthyroid patients with T2DM. Exactly 708 euthyroid adults with T2DM were retrospectively enrolled. The FT3/FT4 ratio was used to estimate peripheral TH sensitivity. Central TH sensitivity was assessed using the Thyrotroph T4 Resistance Index (TT4RI), Thyroid-Stimulating Hormone Index (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Parametric TFQI (PTFQI). DPN was assessed using neurologic symptoms, signs, and nerve conduction velocity tests. The relationship between DPN and TH sensitivity was examined using logistic regression analysis. We observed that an elevated FT3/FT4 ratio was associated with DPN (OR = 1.36, 95%CI: 1.13-1.63, p = 0.0012). For each standard deviation (SD) increase in the TT4RI, TSHI, TFQI, and PTFQI, the OR of DPN was 0.80 (95%CI: 0.68-0.94, p = 0.0078), 0.72 (95%CI: 0.60-0.86, p = 0.0002), 0.69 (95%CI: 0.58-0.83, p < 0.0001), and 0.69 (95%CI: 0.58-0.82, p < 0.0001), respectively. These results suggested that reduced central and peripheral TH sensitivity is associated with a decreased risk of developing DPN.

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.

Promotion of tumor angiogenesis and growth induced by low-dose antineoplastic agents via bone-marrow-derived cells in tumor tissues.

Background: More research is needed to solidify the basis for reasonable metronomic chemotherapy regimens due to the inconsistent clinical outcomes from studies on metronomic chemotherapy with antineoplastic agents, along with signs of a nonlinear dose-response relationship at low doses. The present study therefore explored the dose-response relationships of representative antineoplastic agents in low dose ranges and their underlying mechanisms. Methods: Cyclophosphamide (CPA) and 5-fluorouracil (5-Fu) were employed to observe the effects of the frequent administration of low-dose antineoplastic agents on tumor growth, tumor angiogenesis, and bone-marrow-derived cell (BMDC) mobilization in mouse models. The effects of antineoplastic agents on tumor and endothelial cell functions with or without BMDCs were analyzed in vitro. Results: Tumor growth and metastasis were significantly promoted after the administration of CPA or 5-Fu at certain low dose ranges, and were accompanied by enhanced tumor angiogenesis and proangiogenic factor expression in tumor tissues, increased proangiogenic BMDC release in the circulating blood, and augmented proangiogenic BMDC retention in tumor tissues. Low concentrations of CPA or 5-Fu were found to significantly promote tumor cell migration and invasion, and enhance BMDC adhesion to endothelial cells in vitro. Conclusion: These results suggest that there are risks in empirical metronomic chemotherapy using low-dose antineoplastic agents and the optimal dosage and administration schedule of antineoplastic agents need to be determined through further research.

Joint GWAS and WGCNA Identify Genes Regulating the Isoflavone Content in Soybean Seeds.

Isoflavone is a secondary metabolite of the soybean phenylpropyl biosynthesis pathway with physiological activity and is beneficial to human health. In this study, the isoflavone content of 205 soybean germplasm resources from 3 locations in 2020 showed wide phenotypic variation. A joint genome-wide association study (GWAS) and weighted gene coexpression network analysis (WGCNA) identified 33 single-nucleotide polymorphisms and 11 key genes associated with soybean isoflavone content. Gene ontology enrichment analysis, gene coexpression, and haplotype analysis revealed natural variations in the Glyma.12G109800 (GmOMT7) gene and promoter region, with Hap1 being the elite haplotype. Transient overexpression and knockout of GmOMT7 increased and decreased the isoflavone content, respectively, in hairy roots. The combination of GWAS and WGCNA effectively revealed the genetic basis of soybean isoflavone and identified potential genes affecting isoflavone synthesis and accumulation in soybean, providing a valuable basis for the functional study of soybean isoflavone.

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.

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.

The impact of insomnia on brain networks topology in depressed patients: A resting-state fMRI study.

OBJECTIVE: Depression and insomnia frequently co-occur, but the neural mechanisms between patients with varying degrees of these conditions are not fully understood. The specific topological features and connectivity patterns of this co-morbidity have not been extensively studied. This study aimed to investigate the topological characteristics of topological characteristics and functional connectivity of brain networks in depressed patients with insomnia. METHODS: Resting-state functional magnetic resonance imaging data from 32 depressed patients with a high level of insomnia (D-HI), 35 depressed patients with a low level of insomnia (D-LI), and 81 healthy controls (HC) were used to investigate alterations in brain topological organization functional networks. Nodal and global properties were analyzed using graph-theoretic techniques, and network-based statistical analysis was employed to identify changes in brain network functional connectivity. RESULTS: Compared to the HC group, both the D-HI and D-LI groups showed an increase in the global efficiency (Eglob) values, local efficiency (Eloc) was decreased in the D-HI group, and Lambda and shortest path length (Lp) values were decreased in the D-LI group. At the nodal level, the right parietal nodal clustering coefficient (NCp) values were reduced in D-HI and D-LI groups compared to those in HC. The functional connectivity of brain networks in patients with D-HI mainly involves default mode network (DMN)-cingulo-opercular network (CON), DMN-visual network (VN), DMN-sensorimotor network (SMN), and DMN-cerebellar network (CN), while that in patients with D-LI mainly involves SMN-CON, SMN-SMN, SMN-VN, and SMN-CN. The values of the connection between the midinsula and postoccipital gyrus was negatively correlated with scores for early awakening in D-HI. CONCLUSION: These findings may contribute to our understanding of the underlying neuropsychological mechanisms in depressed patients with insomnia.

An efficient method to generate near-ideal hollow beams of different shapes for box potential of quantum gases.

Ultracold quantum gases are usually prepared in conservative traps for quantum simulation experiments. The atomic density inhomogeneity, together with the consequent position-dependent energy and time scales of cold atoms in traditional harmonic traps, makes it difficult to manipulate and detect the sample at a higher level. These problems are partially solved by optical box traps made of blue-detuned hollow beams. However, generating a high-quality hollow beam with high light efficiency for the box trap is challenging. Here, we present a scheme that combines the fixed optics, including axicons and prisms, to pre-shape a Gaussian beam into a hollow beam with a digital micromirror device (DMD) to improve the quality of the hollow beam further, providing a nearly ideal optical potential of various shapes for preparing highly homogeneous cold atoms. The highest power-law exponent of potential walls can reach a value over 100, and the light efficiency from a Gaussian to a hollow beam is also improved compared to direct optical shaping by a mask or a DMD. Combined with a one-dimensional optical lattice, a nearly ideal two-dimensional uniform quantum gas with different geometrical boundaries can be prepared for exploring quantum many-body physics to an unprecedented level.