Dynamic changes in RNA m6A and 5 hmC influence gene expression programs during macrophage differentiation and polarisation.

RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While m6A has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised. We profiled m6A and 5 hmC epitranscriptomes, transcriptomes, translatomes and proteomes of monocytes and macrophages at rest and pro- and anti-inflammatory states. Transcriptome-wide mapping of m6A and 5 hmC reveals enrichment of m6A and/or 5 hmC on specific categories of transcripts essential for macrophage differentiation. Our analyses indicate that m6A and 5 hmC modifications are present in transcripts with critical functions in pro- and anti-inflammatory macrophages. Notably, we also discover the co-occurrence of m6A and 5 hmC on alternatively-spliced isoforms and/or opposing ends of the untranslated regions (UTR) of mRNAs with key roles in macrophage biology. In specific examples, RNA 5 hmC controls the decay of transcripts independently of m6A. This study provides (i) a comprehensive dataset to interrogate the role of RNA modifications in a plastic system (ii) a resource for exploring different layers of gene expression regulation in the context of human monocyte-to-macrophage differentiation and polarisation, (iii) new insights into RNA modifications as central regulators of effector cells in innate immunity.

Flexible Multimodal Sensing System Based on a Vertical Stacking Strategy for Efficiently Decoupling Multiple Signals.

Multisensory integration enables the simultaneous perception of multiple environmental stimuli while minimizing size and energy consumption. However, conventional multifunctional integration in flexible electronics typically requires large-scale horizontal sensing arrays (such as flexible printed circuit boards), posing decoupling complexities, tensile strain limitation, and spatial constraints. Herein, a fully flexible multimodal sensing system (FMSS) is developed by coupling biomimetic stretchable conductive films (BSCFs) and strain-insensitive communication interfaces using a vertical stacking integration strategy. The FMSS achieves vertical integration without additional adhesives, and it can incorporate individual sensing layers and stretchable interconnects without any essential constraint on their deformations. Accordingly, the temperature and pressure are precisely decoupled simultaneously, and tensile stress can be accurately discerned in different directions. This vertical stacking integration strategy is expected to offer a new approach to significantly streamline the design and fabrication of multimodal sensing systems and enhance their decoupling capabilities.

Upgraded and Light-Up Biosensing Platform: Entropy-Driven Catalysis Circuit Manipulates the Configuration Transformation of Novel DNA Silver Nanoclusters on the Graphene Oxide Surface.

To tackle the predicament of the traditional turn-off mechanism, exploring an activated turn-on system remains an intriguing and crucial objective in biosensing fields. Herein, a dark DNA Ag nanocluster (NC) with hairpin-structured DNA containing a six-base cytosine loop (6C loop) as a template is atypically synthesized. Intriguingly, the dark DNA Ag NCs can be lit to display strong red-emission nanoclusters. Building upon these exciting findings, an unprecedented and upgraded turn-on biosensing system [entropy-driven catalysis circuit (EDCC)-Ag NCs/graphene oxide (GO)] has been created, which employs an EDCC to precisely manipulate the conformational transition of DNA Ag NCs on the GO surface from adsorption to desorption. Benefiting from the effective quenching of GO and signal amplification capability of the EDCC, the newly developed EDCC-Ag NCs/GO biosensing system displays a high signal-to-background (S/B) ratio (26-fold) and sensitivity (limit of detection as low as 0.4 pM). Meanwhile, it has good specificity, excellent stability, and reliability in both buffer and biological samples. To the best of our knowledge, it is the first example that adopts an EDCC to precisely modulate the configuration transformation of DNA Ag NCs on the GO surface to obtain a biosensor with low background, strong fluorescence, high contrast, and sensitivity. This exciting finding may provide a new route to fabricate a novel turn-on biosensor based on hairpin-templated DNA Ag NCs in the optical imaging and bioanalytical fields.

Injectable Oxygen-Carrying Microsphere Hydrogel for Dynamic Regulation of Redox Microenvironment of Wounds.

The delayed healing of infected wounds can be attributed to the increased production of reactive oxygen species (ROS) and consequent damages to vascellum and tissue, resulting in a hypoxic wound environment that further exacerbates inflammation. Current clinical treatments including hyperbaric oxygen therapy and antibiotic treatment fail to provide sustained oxygenation and drug-free resistance to infection. To propose a dynamic oxygen regulation strategy, this study develops a composite hydrogel with ROS-scavenging system and oxygen-releasing microspheres in the wound dressing. The hydrogel itself reduces cellular damage by removing ROS derived from immune cells. Simultaneously, the sustained release of oxygen from microspheres improves cell survival and migration in hypoxic environments, promoting angiogenesis and collagen regeneration. The combination of ROS scavenging and oxygenation enables the wound dressing to achieve drug-free anti-infection through activating immune modulation, inhibiting the secretion of pro-inflammatory cytokines interleukin-6, and promoting tissue regeneration in both acute and infected wounds of rat skins. Thus, the composite hydrogel dressing proposed in this work shows great potential for dynamic redox regulation of infected wounds and accelerates wound healing without drugs.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Ratiometric electrochemiluminescence sensing and intracellular imaging of ClO- via resonance energy transfer.

Electrochemiluminescence resonance energy transfer (ECL-RET) is a versatile signal transduction strategy widely used in the fabrication of chem/biosensors. However, this technique has not yet been applied in visualized imaging analysis of intracellular species due to the insulating nature of the cell membrane. Here, we construct a ratiometric ECL-RET analytical method for hypochlorite ions (ClO-) by ECL luminophore, with a luminol derivative (L-012) as the donor and a fluorescence probe (fluorescein hydrazide) as the acceptor. L-012 can emit a strong blue ECL signal and fluorescein hydrazide has negligible absorbance and fluorescence signal in the absence of ClO-. Thus, the ECL-RET process is turned off at this time. In the presence of ClO-, however, the closed-loop hydrazide structure in fluorescein hydrazide is opened via specific recognition with ClO-, accompanied with intensified absorbance and fluorescence signal. Thanks to the spectral overlap between the ECL spectrum of L-012 and the absorption spectrum of fluorescein, the ECL-RET effect is gradually recovered with the addition of ClO-. Furthermore, the ECL-RET system has been successfully applied to image intracellular ClO-. Although the insulating nature of the cell itself can generate a shadow ECL pattern in the cellular region, extracellular ECL emission penetrates the cell membrane and excites intracellular fluorescein generated by the reactions between fluorescein hydrazide and ClO-. The cell imaging strategy via ECL-RET circumvents the blocking of the cell membrane and enables assays of intracellular species. The importance of the ECL-RET platform lies in calibrating the fluctuation from the external environment and improving the selectivity by using fluorescent probes. Therefore, this ratiometric ECL sensor has shown broad application prospects in the identification of targets in clinical diagnosis and environmental monitoring.

Controlling the spin current around the rectangular cavities in two-dimensional topological insulators.

Controlling spin current in topological insulators (TIs) is a crucial requirement for applications in quantum computing and spintronics. Using the non-equilibrium Keldysh Green's function formalism, we demonstrate that such control can be established around rectangular cavities of two-dimensional TIs by breaking their time reversal symmetry via exchange magnetic fields and magnetic defects. In the presence of magnetic defects with xy symmetry or Ising symmetry, the density of states is localized, and the spin current forms a current loop around the rectangular cavity in TIs interfacing with two ferromagnetic stripes. We also observe that the spin direction of the traveling electrons is inverted under the reversal of bias and gate voltages. The change in the spin-polarized current around the cavities is predicted by varying the strength of Rashba spin-orbit coupling. This result allows for the creation and control of nearly fully spin-polarized currents with various spatial patterns around the cavities in TIs, and the design of tunable spin diodes for highly integrated spintronics.

Studies on the Relationships between Growth and Gonad Development during First Sexual Maturation of Macrobrachium nipponense and Associated SNPs Screening.

In this study, we used full-sib families to investigate the association between growth and gonad development during first sexual maturation of M. nipponense. We found that male GSI was significantly negatively correlated with growth traits (p < 0.01) and there were no significant correlations between female GSI (Gonadosomatic index) and growth traits (p > 0.05). HSI (Hepatopancreas index) in both males and females showed no significant correlations with growth traits (p > 0.05). We furthermore investigated the association between the specific allele of Mn-CTS L1 polymorphism and gonad development and growth traits. In total, 35 mutation loci were screened and 16 high-quality single-nucleotide polymorphisms (SNPs) loci were obtained after validation. Four and two SNPs proved to be strongly associated with all growth traits in female and male M. nipponense separately, among which A+118T might be a candidate SNP positively associated with large growth traits. Two and one SNPs were screened, respectively, in males and females to associate with GSI, while three SNPs were detected to associate with female HSI, among which A+1379C may be applied as a potential molecular marker for gene-assisted selection to improve both reproduction speed and growth traits in M. nipponense.

Genome-Wide Association Analysis of Effective Tillers in Rice under Different Nitrogen Gradients.

Nitrogen is a crucial element that impacts rice yields, and effective tillering is a significant agronomic characteristic that can influence rice yields. The way that reduced nitrogen affects effective tillering is a complex quantitative trait that is controlled by multiple genes, and its genetic basis requires further exploration. In this study, 469 germplasm varieties were used for a genome-wide association analysis aiming to detect quantitative trait loci (QTL) associated with effective tillering at low (60 kg/hm2) and high (180 kg/hm2) nitrogen levels. QTLs detected over multiple years or under different treatments were scrutinized in this study, and candidate genes were identified through haplotype analysis and spatio-temporal expression patterns. A total of seven genes (NAL1, OsCKX9, Os01g0690800, Os02g0550300, Os02g0550700, Os04g0615700, and Os04g06163000) were pinpointed in these QTL regions, and were considered the most likely candidate genes. These results provide favorable information for the use of auxiliary marker selection in controlling effective tillering in rice for improved yields.

A Cost-Effective Sulfide Solid Electrolyte Li7P3S7.5O3.5 with Low Density and Excellent Anode Compatibility.

The commercialization of all-solid-state Li batteries (ASSLBs) demands solid electrolytes with strong cost-competitiveness, low density (for enabling satisfactory energy densities), and decent anode compatibility (the need for cathode compatibility can be circumvented by the cathode coating techniques that are widely applied in sulfide-based ASSLBs). However, none of the reported oxide, sulfide, or chloride solid electrolytes meets these requirements simultaneously. Here, we design a Li7P3S7.5O3.5 (LPSO) solid electrolyte, which shows a combination of all the aforementioned characteristics. The synthesis of this material does not need the expensive Li2S, so the raw materials cost is only $14.42/kg, which, unlike most solid electrolytes, lies below the $50/kg threshold for commercialization. The density of LPSO is 1.70 g cm-3, considerably lower than those of the oxide (typically above 5 g cm-3) and chloride (around 2.5 g cm-3) solid electrolytes. Besides, LPSO also shows excellent anode compatibility. The Li|LPSO|Li cell cycles stably with a potential of ~50 mV under 0.1 mA cm-2 for over 4200 h at 25 °C, and the all-solid-state pouch cell with the Si anode shows a capacity retention of 89.29 % after 200 cycles under 88.6 mA g-1 at 60 °C.

Design and Catalytic Asymmetric Synthesis of Furan-Indole Compounds Bearing both Axial and Central Chirality.

In the chemistry community, catalytic asymmetric synthesis of furan-based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing to the importance and difficulty in constructing such frameworks. In this work, we have realized the first catalytic asymmetric synthesis of five-five-membered furan-based compounds bearing both axial and central chirality via organocatalytic asymmetric (2+4) annulation of achiral furan-indoles with 2,3-indolyldimethanols with uncommon regioselectivity. By this strategy, furan-indole compounds bearing both axial and central chirality were synthesized in high yields with excellent regio-, diastereo-, and enantioselectivities. Moreover, theoretical calculations were conducted to provide an in-depth understanding of the reaction pathway, activation mode, and the origin of the selectivity.

[The mediating effects of self-efficacy between symptom experience and quality of life in prostatic hyperplasia patients after cystostomy].

OBJECTIVE: To evaluate the symptom experience of patients with benign prostatic hyperplasia and bladder fistula. Exploring the mediating effect of self-efficacy on the relationship between symptom experience and quality of life in patients with benign prostatic hyperplasia undergoing long-term indwelling cystostomy. METHODS: This study used a cross-sectional survey design. Patients with prostatic hyperplasia with cystostomy in the Urology department of General Hospital of Eastern Theater Command from January 2020 to February 2023 were selected, and relevant data were collected by IPSS, IIEF-5, HAMD, GSES, and quality of life score scale for statistical analysis. We then construct a structural equation model to evaluate the mediating effect of self-efficacy between symptom experience and quality of life. RESULTS: The average score of IPSS was (22.55±8.26) ; the average score of IIEF-5 was (10.54±4.10) ; the average score of HAMD was (6.82±2.35) ; the average score of self-efficacy was (20.80±8.65) ; and the average score of quality of life was (71.65±12.55) . Symptom experience was significantly negatively correlated with self-efficacy and quality of life( r=－0.496 , P<0.01；r=－0.518 , P<0.01) . Self-efficacy was significantly positively correlated with quality of life( r= 0.412，P<0.05). Symptom experience significantly negatively affected quality of life through self-efficacy (Effect = －0.218，P = 0.014) . CONCLUSION: Self-efficacy is positively correlated with the quality of life of patients with benign prostatic hyperplasia who have long-term indwelling cystostomy tube. Nursing staff can improve the level of self-efficacy of patients by implementing corresponding interventions.

Knowledge, Attitudes and Practices Toward Physical Literacy Among the College Students During COVID-19 School Closure.

Purpose: To investigate the knowledge, attitudes and practices (KAP) among college students toward physical literacy during COVID-19 school closure. Patients and Methods: This web-based cross-sectional study was conducted between December 9th, 2022 and December 24th, 2022 among college students during COVID-19 school closure. A self-designed questionnaire was developed to collect demographic information of the college students, and assess their KAP toward physical literacy. Results: A total of 969 students were recruited, with mean age of 18.73±0.97 years. The majority were male (54.70%), urban residents (78.02%), majoring in engineering (58.00%), and having exercise habits (61.09%). The mean KAP scores were 6.57±0.95, 32.63±4.07, and 27.06±7.23, respectively. Positive associations were identified between knowledge and attitude (OR = 2.01, 95% CI: 1.52-2.66, P < 0.001), and between attitude and practice (OR = 1.17, 95% CI: 1.12-1.22, P < 0.001). A bachelor's degree and being in the sophomore year were positively associated with knowledge (OR = 1.51-4.05, all P < 0.05). Urban residence and being in the sophomore year were negatively associated with attitude (OR = 0.43-0.59, all P < 0.05), while having daily exercise habits showed the opposite trend (OR = 1.85, 95% CI: 1.33-2.57, P < 0.001). Father's education level of high school and technical secondary school (OR = 0.58, 95% CI: 0.37-0.93, P = 0.023) and having daily exercise habits (OR = 3.88, 95% CI: 2.72-5.55, P < 0.001) were associated with practice. Conclusion: College students had sufficient knowledge, moderate attitudes and negative practices towards physical literacy during COVID-19 school closure. The findings hold significant potential for developing educational programs, fostering healthier lifestyles and promoting mental well-being among college students during public health outbreaks.

Signaling pathways regulating the extracellular digestion of lipoprotein aggregates by macrophages.

The interaction between aggregated low-density lipoprotein (agLDL) and macrophages in arteries plays a major role in atherosclerosis. Macrophages digest agLDL and generate free cholesterol in an extracellular, acidic, hydrolytic compartment known as the lysosomal synapse. Macrophages form a tight seal around agLDL through actin polymerization and deliver lysosomal contents into this space in a process termed digestive exophagy. Our laboratory has identified TLR4 activation of MyD88/Syk as critical for digestive exophagy. Here we use pharmacological agents and siRNA knockdown to characterize signaling pathways downstream of Syk that are involved in digestive exophagy. Syk activates Bruton's tyrosine kinase (BTK) and phospholipase Cγ2 (PLCγ2). We show that PLCγ2 and to a lesser extent BTK regulate digestive exophagy. PLCγ2 cleaves PI(4,5)P2 into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Soluble IP3 activates release of Ca2+ from the endoplasmic reticulum (ER). We demonstrate that Ca2+ release from the ER is upregulated by agLDL and plays a key role in digestive exophagy. Both DAG and Ca2+ activate protein kinase Cα (PKCα). We find that PKCα is an important regulator of digestive exophagy. These results expand our understanding of the mechanisms of digestive exophagy, which could be useful in developing therapeutic interventions to slow development of atherosclerosis.

Human brain glycoform coregulation network and glycan modification alterations in Alzheimer's disease.

Despite the importance of protein glycosylation to brain health, current knowledge of glycosylated proteoforms or glycoforms in human brain and their alterations in Alzheimer's disease (AD) is limited. Here, we report a proteome-wide glycoform profiling study of human AD and control brains using intact glycopeptide-based quantitative glycoproteomics coupled with systems biology. Our study identified more than 10,000 human brain N-glycoforms from nearly 1200 glycoproteins and uncovered disease signatures of altered glycoforms and glycan modifications, including reduced sialylation and N-glycan branching and elongation as well as elevated mannosylation and N-glycan truncation in AD. Network analyses revealed a higher-order organization of brain glycoproteome into networks of coregulated glycoforms and glycans and discovered glycoform and glycan modules associated with AD clinical phenotype, amyloid-ß accumulation, and tau pathology. Our findings provide valuable insights into disease pathogenesis and a rich resource of glycoform and glycan changes in AD and pave the way forward for developing glycosylation-based therapies and biomarkers for AD.

Frequency-to-Place Mismatch Impacts Cochlear Implant Quality of Life, But Not Speech Recognition.

OBJECTIVE: To retrospectively compare frequency-place mismatch among adult cochlear implant (CI) recipients with lateral wall (LW) and perimodiolar/Mid Scala (PM/MS) arrays, and to quantify the impact of these factors on early post-activation (3 months) speech recognition abilities and CI-specific quality of life. METHODS: One hundred and twenty-six adult participants were separated into two groups: (1) 83 participants who underwent CI with a PM/MS array and 43 patients who underwent CI with a LW array. All participants completed the Cochlear Implant Quality of Life Profile (CIQOL-35 Profile) instrument. Angular insertion depth and semitone mismatch, which contribute to frequency-place mismatch, were assessed using post-operative CT scans. Word and speech recognition in quiet were determined using the Consonant-Nucleus-Consonant (CNC) and the AzBio tests, respectively (n = 82 patients). RESULTS: LW arrays were more deeply inserted and exhibited less semitone mismatch compared to PM/MS arrays. No significant relationship was found between semitone mismatch and early post-operative speech perception scores for either PM/MS or LW arrays. However, greater degrees of semitone mismatch were associated with lower CIQOL-35 profile scores for PM/MS arrays. CONCLUSIONS AND RELEVANCE: The results of this study indicate that both the degree of frequency-place mismatch, and its impact on CI-specific quality of life, vary by CI array design. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2898-2905, 2024.

Oxygenation heterogeneity facilitates spatiotemporal flow pattern visualization inside human blood vessels using photoacoustic computed tomography.

Hemodynamics can be explored through various biomedical imaging techniques. However, observing transient spatiotemporal variations in the saturation of oxygen (sO2) within human blood vessels proves challenging with conventional methods. In this study, we employed photoacoustic computed tomography (PACT) to reconstruct the evolving spatiotemporal patterns in a human vein. Through analysis of the multi-wavelength photoacoustic (PA) spectrum, we illustrated the dynamic distribution within blood vessels. Additionally, we computationally rendered the dynamic process of venous blood flowing into the major vein and entering a branching vessel. Notably, we successfully recovered, in real time, the parabolic wavefront profile of laminar flow inside a deep vein in vivo-a first-time achievement. While the study is preliminary, the demonstrated capability of dynamic sO2 imaging holds promise for new applications in biology and medicine.

The water extract of Rheum palmatum has antioxidative properties and inhibits ROS production in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum (RP) is a widely used traditional herb, which possesses antioxidant properties, inhibits ROS production and reduces fever. AIM OF THE STUDY: The aim of this study was to examine the antioxidative properties of the water extract of RP on oxidative-stressed mice. MATERIALS & METHODS: Forty mice were administered with DL-homocysteine (DL-Hcy) to induce oxidative stress and were divided into four groups: 1) CK: NaCl and water; 2) DL-Hcy: DL-Hcy and water; 3) DL-Hcy+50RP: DL-Hcy with 50 mg kg-1 body weight (BW) d-1 RP; and 4) DL-Hcy+150RP: DL-Hcy with 150 mg kg-1 BW d-1 RP. Rhein (0.3 mg g-1 dry matter) was the main active ingredient in RP. RESULTS: When compared with Dl-Hcy mice, the mice with supplementary RP mitigated oxidative stress by reducing the liver concentrations of superoxide dismutase (SOD) by 27% and glutathione peroxidase (GSH-Px) by 32%, and the reactive oxygen species (ROS) in the kidney and spleen. These responses were more pronounced in DL-Hcy+150RP than DL-Hcy+50RP mice. RP also exhibited therapeutic effects on liver steatosis, chronic kidney nephritis and intestinal villus width shortening caused by oxidative stress, and concomitantly decreased the serum glucose concentration (RP vs. DL-HCY, 2.3 vs. 4.1 mmol L-1). CONCLUSION: It was concluded that RP possesses antioxidant and therapeutic properties that can mitigate lesions on organs and prevent diabetes in oxidative-stressed mice. This study highlights the potential of RP as a medicinal supplement for animals in the future.

Monte Carlo-Based Optical Simulation of Optical Distribution in Deep Brain Tissues Using Sixteen Optical Sources.

Optical-based imaging has improved from early single-location research to further sophisticated imaging in 2D topography and 3D tomography. These techniques have the benefit of high specificity and non-radiative safety for brain detection and therapy. However, their performance is limited by complex tissue structures. To overcome the difficulty in successful brain imaging applications, we conducted a simulation using 16 optical source types within a brain model that is based on the Monte Carlo method. In addition, we propose an evaluation method of the optical propagating depth and resolution, specifically one based on the optical distribution for brain applications. Based on the results, the best optical source types were determined in each layer. The maximum propagating depth and corresponding source were extracted. The optical source propagating field width was acquired in different depths. The maximum and minimum widths, as well as the corresponding source, were determined. This paper provides a reference for evaluating the optical propagating depth and resolution from an optical simulation aspect, and it has the potential to optimize the performance of optical-based techniques.