Chromosome-scale genome assembly for soft-stem bulrush (Schoenoplectus tabernaemontani) confirms a clade-specific whole genome duplication in Cyperaceae.

Schoenoplectus tabernaemontani (C. C. Gmelin) Palla is a typical macrophyte in diverse wetland ecosystems. This species holds great potential in decontamination applications and carbon sequestration. Previous studies have shown that this species may have experienced recent polyploidization. This would make S. tabernaemontani a unique model to study the processes and consequences of whole genome duplications in the context of the well-documented holocentric chromosomes and dysploidy events in Cyperaceae. However, the inference was not completely solid because it lacked homology information which is essential to ascertain polyploidy. We present here the first chromosome-level genome assembly for S.tabernaemontani. By combining ONT long-reads and Illumina short-reads, plus chromatin conformation via the Hi-C method, we assembled a genome spanning 507.96 Mb, with 99.43% of Hi-C data accurately mapped to the assembly. The assembly contig N50 value was 3.62 Mb. The overall BUSCO score was 94.40%. About 68.94% of the genome was comprised of repetitive elements. 36994 protein-coding genes were predicted and annotated. Long terminal repeat retrotransposons (LTR-rts) accounted for approximate 26.99% of the genome, surpassing the content observed in most sequenced Cyperid genomes. Our well-supported haploid assembly comprised 21 pseudochromosomes, each harboring putative holocentric centromeres. Our findings corroborated a karyotype of 2n=2X=42. We also confirmed a recent whole genome duplication (WGD) occurring after the divergence between Schoenoplecteae and Bolboschoeneae. Our genome assembly expands the scope of sequenced genomes within the Cyperaceae family, encompassing the fifth genus. It also provides research resources on Cyperid evolution and wetland conservation.

Active myeloperoxidase: a promising biomarker to differentiate "acute" and "low-grade" peri-prosthetic joint infections from aseptic failures.

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI. Methods: Synovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant. Results: Active MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78-0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11-83.81%, positive likelihood ratio 5.88, 95% CI: 2.31-14.98 and negative likelihood ratio 0.35, 95%CI: 0.24-0.51). No difference in MPO levels was found between acute and chronic low-grade PJI. Conclusion: The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

High-Pressure Molecular Sieving of High-Humidity C2H4/C2H6 Mixture by a Hydrophobic Flexible Metal-Organic Framework.

Molecular sieving is an ideal separation mechanism, but controlling pore size, restricting framework flexibility, and avoiding strong adsorption are all very challenging. Here, we report a flexible adsorbent showing molecular sieving at ambient temperature and high pressure, even under high humidity. While typical guest-induced transformations are observed, a high transition pressure of 16.6 atm is observed for C2H4 at 298 K because of very weak C2H4 adsorption (~16 kJ mol-1). Also, C2H6 is completely excluded below the pore-opening pressure of 7.7 atm, giving single-component selectivity of ca. 300. Quantitative high-pressure column breakthrough experiments using 1:1 C2H4/C2H6 mixture at 10 atm as input confirms molecular sieving with C2H4 adsorption of 0.73 mmol g-1 or 32 cm3(STP) cm-3 and negligible C2H6 adsorption of 0.001(2) mmol g-1, and the adsorbent can be completely regenerated by inert gas purging. Furthermore, it is highly hydrophobic with negligible water adsorption, and the C2H4/C2H6 separation performance is unaffected at high humidity.

Experimental Study on Mechanical Properties and Permeability Characteristics of Calcareous Mudstone under Different Confining Pressures.

Calcareous mudstone, a type of red-bed soft rock, is prevalent in the surrounding rock of the Central Yunnan Water Diversion Project (CYWDP) in Yunnan Province, China, significantly impacting both construction and operation. The mechanical properties of calcareous mudstone vary with depth. This study investigates its mechanical properties, permeability characteristics, energy evolution, and macro- and micro-failure characteristics during deformation using triaxial compression tests under different confining pressures. Results reveal distinct stage characteristics in the stress-strain behavior, permeability, and energy evolution of calcareous mudstone. Crack propagation, permeability evolution, and energy dissipation are closely linked, elucidating the deformation and failure process, with fluid pressure playing a crucial role. The confining pressure σ3 increased from 2 MPa to 4 MPa and 6 MPa, while the peak stress σc (Pw = 1 MPa) of the calcareous mudstone increased by 84.49% and 24.89%, respectively. Conversely, the permeability at σc decreased from 11.25 × 10-17 m2 to 8.99 × 10-17 m2 and 5.72 × 10-17 m2, while the dissipative energy at σc increased from 12.39 kJ/m3 to 21.14 kJ/m3 and 42.51 kJ/m3. In comparison to those without fluid pressure (Pw = 0), the value of σc at Pw = 1 MPa was reduced by 36.61%, 23.23%, and 20.67% when σ3 was 2, 4, and 6 MPa, respectively. Increasing confining pressure augments characteristic stresses, deformation and failure energy, and ductility, while reducing permeability, crack propagation, and width. These findings enhance our understanding of calcareous mudstone properties at varying depths in tunnel construction scenarios.

2 × 4†kW near-single-mode laser output assisted by an optimized bidirectional oscillating-amplifying integrated fiber laser configuration.

Bidirectional output oscillating-amplifying integrated fiber laser (B-OAIFL) can achieve the two-ports laser amplification based on a single cavity, showcasing a promising prospect. In order to improve both the laser power and beam quality, we first simulate and optimize the stimulated Raman scattering (SRS) effect in the B-OAIFL. The simulation results show the SRS effect can be suppressed by optimizing the diameter as well as the length of the active fiber at different locations. With the guidance of theoretical and experimental analysis for the combined suppression of SRS and transverse mode instability (TMI), a near-single-mode B-OAIFL with 2 × 4 kW was demonstrated. Based on this foundation, we further devoted ourselves to the pursuit of the optimization of the structure and performance. The necessity of the configuration of side pump, which was initially introduced for its exceptional performance in stabilizing temporal chaos, was reevaluated in detail. With its negative impacts on efficiency improvement and SRS suppression were analyzed and verified, we removed this configuration and finally demonstrated a more simplified design with superior performance. A total bidirectional output of 8105 W was achieved, with an O-O efficiency of 79.6% and a near-single-mode beam quality of M A 2∼1.36,M B 2∼1.63. No signs of TMI were observed, and the signal-to-SRS suppression ratio was over 38 dB. The results still demonstrate a promising potential for power scaling based on this configuration and parameters.

Highly oxidized guaiane 12(8),15(6)-dilactones with neuroprotective activities from the roots of Lindera aggregata (Sims) Kosterm.

In our search for neuroprotective agents, six previously undescribed highly oxidized guaiane sesquiterpenes, linderaggrols A-F (1-6), together with three known sesquiterpenes, were isolated from the roots of Lindera aggregata (Sims) Kosterm. Their structures including absolute configurations were established by a combination of NMR spectroscopic techniques and single crystal X-ray diffraction experiments. Compounds 1-6 represented the first instances of guaiane 12(8),15(6)-dilactones. Additionally, compound 6 possessed a rare 1,8-O-bridge. Neuroprotective effects against erastin-induced ferroptosis on HT-22 cells showed that some compounds demonstrated neuroprotective effects at 20.0 µM.

Design, synthesis and biological evaluation of new RNF126-based p300/CBP degraders.

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.

Diagnosis of Canine Tumours and the Value of Combined Detection of VEGF, P53, SF and NLRP3 for the Early Diagnosis of Canine Mammary Carcinoma.

The average life of a dog is generally maintained at ten to fifteen years, and tumours are the predominant reason that leads to the death of dogs, especially canine mammary carcinoma. Therefore, early diagnosis of tumours is very important. In this study, tumor size, morphology, and texture could be seen through general clinical examination, tumor metastasis could be seen through imaging examination, inflammatory reactions could be seen through hematological examination, and abnormal cell morphology could be seen through cytological and histopathological examination. In the 269 malignant cases and 179 benign cases, we randomly selected 30 cases each, and an additional 30 healthy dogs were selected for the experiment (healthy dogs: dogs in good physical condition without any tumor or other diseases). We used RT-qPCR and ELISA to determine the relative expression of vascular endothelial growth factor (VEGF), tumor protein P53 (P53), serum ferritin (SF), and NOD-like receptor protein 3 (NLRP3) in 30 healthy dogs, 30 dogs with benign mammary tumours, and 30 dogs with malignant mammary tumours. In the results, the same expression trend was obtained both in serum and tissues, and the expression of the four markers was the highest in malignant mammary tumours, with highly significant differences compared with the benign and healthy/paracancerous groups. By plotting the ROC curves, it was found that the results of combined tests were better than a single test and the combination of the four markers was the best for the early diagnosis. In conclusion, this can assist the clinical early diagnosis to a certain extent, and also provides some references and assistance for the development of tumor detection kits in clinical practice.

Consensus statement of Chinese experts on exercise prescription (2023).

Exercise prescriptions play a vital role in the prevention and treatment of chronic diseases. A consensus regarding exercise prescription is important for physical health. The "Consensus statement of Chinese experts on exercise prescription" (hereinafter referred to as "Expert Consensus") divides exercise prescription into two categories: fitness exercise prescription and medical exercise prescription. Traditional Chinese fitness exercises, exercise risk, exercise prescription, and basic precautions for exercise prescription are explained.

Narrative Review and Consensus Recommendations for the Use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange in Modified Electroconvulsive Therapy.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a safe, effective, and novel technique that is currently being used in electroconvulsive therapy (ECT). This study aimed to summarize the clinical practices of THRIVE use in ECT to aid physicians and institutions in implementing the best practice guidelines for ECT. Thus, we reviewed the current literature and presented our consensus on the application of THRIVE in ECT in daily clinical practice. This consensus provides information regarding THRIVE use in ECT, including its safety, effectiveness, procedures, precautions, special case management, and application in special populations. Moreover, it guides the standardized use of THRIVE in ECT.

Enrooted-Type Metal-Support Interaction Boosting Oxygen Evolution Reaction in Acidic Media.

Supported metal catalysts with appropriate metal-support interactions (MSIs) hold a great promise for heterogeneous catalysis. However, ensuring tight immobilization of metal clusters/nanoparticles on the support while maximizing the exposure of surface active sites remains a huge challenge. Herein, we report an Ir/WO3 catalyst with a new enrooted-type MSI in which Ir clusters are, unprecedentedly, atomically enrooted into the WO3 lattice. The enrooted Ir atoms decrease the electron density of the constructed interface compared to the adhered (root-free) type, thereby achieving appropriate adsorption toward oxygen intermediates, ultimately leading to high activity and stability for oxygen evolution in acidic media. Importantly, this work provides a new enrooted-type supported metal catalyst, which endows suitable MSI and maximizes the exposure of surface active sites in contrast to the conventional adhered, embedded, and encapsulated types.

Universal Synthesis of Single-Atom Catalysts by Direct Thermal Decomposition of Molten Salts for Boosting Acidic Water Splitting.

Single-atom catalysts (SACs) are considered prominent materials in the field of catalysis due to their high metal atom utilization and selectivity. However, the wide-ranging applications of SACs remain a significant challenge due to their complex preparation processes. Here, a universal strategy is reported to prepare a series of noble metal single atoms on different non-noble metal oxides through a facile one-step thermal decomposition of molten salts. By using a mixture of non-noble metal nitrate and a small-amount noble metal chloride as the precursor, noble metal single atoms can be easily introduced into the non-noble metal oxide lattice owing to the cation exchange in the in situ formed molten salt, followed by the thermal decomposition of nitrate anions during the heating process. Analyses using aberration-corrected high-angle annular dark-field scanning transmission electron microscopy and extended X-ray absorption fine structure spectroscopy confirm the formation of the finely dispersed single atoms. Specially, the as-synthesized Ir single atoms (10.97 wt%) and Pt single atoms (4.60 wt%) on the Co3O4 support demonstrate outstanding electrocatalytic activities for oxygen evolution reaction and hydrogen evolution reaction, respectively.

Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.

Development of an enzyme-linked phage receptor-binding protein assay (ELPRA) based on a novel biorecognition molecule- receptor-binding protein Gp130 of Pseudomonas aeruginosa bacteriophage Henu5.

Pseudomonas aeruginosa is a Gram-negative bacterium associated with life-threatening healthcare-associated infections (HAIs), including burn wound infections, pneumonia and sepsis. Moreover, P. aeruginosa has been considered a pathogen of global concern due to its rising antibiotic resistance. Efficient identification of P. aeruginosa would significantly benefit the containment of bacterial infections, prevent pathogen transmission, and provide orientated treatment options. The accuracy and specificity of bacterial detection are primarily dictated by the biorecognition molecules employed. Lytic bacteriophages (or phages) could specifically attach to and lyse host bacterial cells. Phages' host specificity is typically determined by their receptor-binding proteins (RBPs), which recognize and adsorb phages to particular bacterial host receptors. This makes RBPs promising biorecognition molecules in bacterial detection. This study identified a novel RBP (Gp130) from the P. aeruginosa phage Henu5. A modified enzyme-linked phage receptor-binding protein assay (ELPRA) was developed for P. aeruginosa detection employing Gp130 as biorecognition molecules. Optimized conditions provided a calibration curve for P. aeruginosa with a range from 1.0 × 103 to 1.0 × 107 CFU/mL, with a limit of detection as low as 10 CFU/mL in phosphate-buffered saline (PBS). With VITEKⓇ 2 Compact system identification (40 positives and 21 negatives) as the gold standard, the sensitivity of ELPRA was 0.950 (0.818-0.991), and the specificity was 0.905 (0.682-0.983) within a 95 %confidence interval. Moreover, the recovery test in spiked mouse serum showed recovery rates ranging from 82.79 %to 98.17%, demonstrating the prospect of the proposed ELPRA for detecting P. aeruginosa in biological samples.

Adsorption behavior and the potential risk of As(V) in soils: exploring the effects of representative surfactants.

Arsenic contamination in soils poses a critical global challenge, yet the influence of surfactants on arsenic adsorption behavior is often underestimated. This study aims to investigate the effects of three representative surfactants, namely cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and polyethylene glycol anhydrous sugar alcohol monooleate (Tween 80), on arsenic adsorption behavior in soils. The adsorption isotherm shifts from a single Temkin model without surfactants to both the Langmuir and Temkin models in the presence of surfactants, indicating the simultaneous occurrence of monolayer and multilayer adsorption for arsenic in soils. Moreover, the surfactants can inhibit the adsorption and hasten the attainment of adsorption equilibrium. SDS displayed the most inhibitory effect on arsenic adsorption, followed by Tween 80 and CTAB, due to the competitive adsorption, electrostatic interaction, and hydrophobic interaction. Variations in zeta potential with different surfactants further elucidate this inhibitory phenomenon. Through orthogonal experiment analyses, pH emerges as a primary factor influencing arsenic adsorption in soils, with surfactant concentration and type identified as secondary factors. Temperature notably affects CTAB, with the adsorption inhibition rate plummeting to a mere 0.88% at 50 °C. Sequential extraction analysis revealed that surfactants enhanced the bioavailability of arsenic. The FTIR, XRD, SEM, and CA analyses further support the mechanism underlying the effect of surfactants on arsenic adsorption in soil. These analyses indicate that surfactants modify the composition and abundance of functional groups, hinder the formation of arsenic-containing substances, and improve soil compactness, smoothness, and hydrophilicity. This study provides valuable insights into the effect of surfactants in arsenic-contaminated soils, which is often ignored in previous work.

Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Chromosome-Scale Genome Assembly for Clubrush (Bolboschoenus planiculmis) Indicates a Karyotype with High Chromosome Number and Heterogeneous Centromere Distribution.

Bolboschoenus planiculmis (F.Schmidt) T.V.Egorova is a typical wetland plant in the species-rich Cyperaceae family. This species contributes prominently to carbon dynamics and trophic integration in wetland ecosystems. Previous studies have reported that the chromosomes of B. planiculmis are holocentric; i.e. they have kinetic activity along their entire length and carry multiple centromeres. This feature was suggested to lead to a rapid genome evolution through chromosomal fissions and fusions and participate to the diversification and ecological success of the Bolboschoenus genus. However, the specific mechanism remains uncertain, partly due to the scarcity of genetic information on Bolboschoenus. We present here the first chromosome-level genome assembly for B. planiculmis. Through the integration of high-quality long-read and short-read data, together with chromatin conformation using Hi-C technology, the ultimate genome assembly was 238.01 Mb with a contig N50 value of 3.61 Mb. Repetitive elements constituted 37.04% of the genome, and 18,760 protein-coding genes were predicted. The low proportion of long terminal repeat retrotransposons (∼9.62%) was similar to that reported for other Cyperaceae species. The Ks (synonymous substitutions per synonymous site) distribution suggested no recent large-scale genome duplication in this genome. The haploid assembly contained a large number of 54 pseudochromosomes with a small mean size of 4.10 Mb, covering most of the karyotype. The results of centromere detection support that not all the chromosomes in B. planiculmis have multiple centromeres, indicating more efforts are needed to fully reveal the specific style of holocentricity in cyperids and its evolutionary significance.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Crystal Engineering of MOF-Derived Bimetallic Oxide Solid Solution Anchored with Au Nanoparticles for Photocatalytic CO2 Reduction to Syngas and C2 Hydrocarbons.

Considering that CO2 reduction is mostly a multielectron reaction, it is necessary for the photocatalysts to integrate multiple catalytic sites and cooperate synergistically to achieve efficient photocatalytic CO2 reduction to various products, such as C2 hydrocarbons. Herein, through crystal engineering, we designed and constructed a metal-organic framework-derived Zr/Ti bimetallic oxide solid solution support, which was confirmed by X-ray diffraction, electron microscopy and X-ray absorption spectroscopy. After anchoring Au nanoparticles, the composite photocatalyst exhibited excellent performances toward photocatalytic CO2 reduction to syngas (H2 and CO production rates of 271.6 and 260.6 µmol g-1 h-1) and even C2 hydrocarbons (C2H4 and C2H6 production rates of 6.80 and 4.05 µmol g-1 h-1). According to the control experiments and theoretical calculations, the strong interaction between bimetallic oxide solid solution support and Au nanoparticles was found to be beneficial for binding intermediates and reducing CO2 reduction, highlighting the synergy effect of the catalytic system with multiple active sites.

Nicorandil-Pretreated Mesenchymal Stem Cell-Derived Exosomes Facilitate Cardiac Repair After Myocardial Infarction via Promoting Macrophage M2 Polarization by Targeting miR-125a-5p/TRAF6/IRF5 Signaling Pathway.

Background: Exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) have been considered as a promising cell-free therapeutic strategy for ischemic heart disease. Cardioprotective drug pretreatment could be an effective approach to improve the efficacy of MSC-exo. Nicorandil has long been used in clinical practice for cardioprotection. This study aimed to investigate whether the effects of exosomes derived from nicorandil pretreated MSC (MSCNIC-exo) could be enhanced in facilitating cardiac repair after acute myocardial infarction (AMI). Methods: MSCNIC-exo and MSC-exo were collected and injected into the border zone of infarcted hearts 30 minutes after coronary ligation in rats. Macrophage polarization was detected 3 days post-infarction, cardiac function as well as histological pathology were measured on the 28th day after AMI. Macrophages were separated from the bone marrow of rats for in vitro model. Exosomal miRNA sequencing was conducted to identify differentially expressed miRNAs between MSCNIC-exo and MSC-exo. MiRNA mimics and inhibitors were transfected to MSCs or macrophages to explore the specific mechanism. Results: Compared to MSC-exo, MSCNIC-exo showed superior therapeutic effects on cardiac functional and structural recovery after AMI and markedly elevated the ratio of CD68+ CD206+/ CD68+cells in infarcted hearts 3 days post-infarction. The notable ability of MSCNIC-exo to promote macrophage M2 polarization was also confirmed in vitro. Exosomal miRNA sequencing and both in vivo and in vitro experiments identified and verified that miR-125a-5p was an effector of the roles of MSCNIC-exo in vivo and in vitro. Furthermore, we found miR-125a-5p promoted macrophage M2 polarization by inhibiting TRAF6/IRF5 signaling pathway. Conclusion: This study suggested that MSCNIC-exo could markedly facilitate cardiac repair post-infarction by promoting macrophage M2 polarization by upregulating miR-125a-5p targeting TRAF6/IRF5 signaling pathway, which has great potential for clinical translation.