A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy.

Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses. This paper presents a thorough examination of the latest progress in CAR-M therapy, covering both basic scientific studies and clinical trials. This study examines the primary obstacles hindering the realization of the complete potential of CAR-M therapy, as well as the potential strategies that can be employed to overcome these hurdles. With the emergence of revolutionary technologies like in situ genetic modification, synthetic biology techniques, and biomaterial-supported gene transfer, which provide a wider array of resources for manipulating tumor-associated macrophages, we suggest that combining these advanced methods will result in the creation of a new era of CAR-M therapy that demonstrates improved efficacy, safety, and availability.

Nanoarchitectonics with a Membrane-Embedded Electron Shuttle Mimics the Bioenergy Anabolism of Mitochondria.

Enhanced bioenergy anabolism through transmembrane redox reactions in artificial systems remains a great challenge. Here, we explore synthetic electron shuttle to activate transmembrane chemo-enzymatic cascade reactions in a mitochondria-like nanoarchitecture for augmenting bioenergy anabolism. In this nanoarchitecture, a dendritic mesoporous silica microparticle as inner compartment possesses higher load capacity of NADH as proton source and allows faster mass transfer. In addition, the outer compartment ATP synthase-reconstituted proteoliposomes. Like natural enzymes in the mitochondrion respiratory chain, a small synthetic electron shuttle embedded in the lipid bilayer facilely mediates transmembrane redox reactions to convert NADH into NAD+ and a proton. These facilitate an enhanced outward proton gradient to drive ATP synthase to rotate for catalytic ATP synthesis with improved performance in a sustainable manner. This work opens a new avenue to achieve enhanced bioenergy anabolism by utilizing a synthetic electron shuttle and tuning inner nanostructures, holding great promise in wide-range ATP-powered bioapplications.

Analysis of five rare alleles at the STR loci D1S1656, D12S391, D13S317, Penta D, and D2S441.

Short tandem repeat (STR) automatic typing technology is extensively used in forensic laboratories with commercial kits, in rare cases genotyping misinterpretations or mislabeling may occur due to unexpected rare alleles. This study refers to the investigation of several rare alleles observed from routine cases. Besides cross-kit verification with Goldeneye 25A (Beijing PeopleSpot Inc, China) and Huaxia platinum (Thermo Fisher Scientific, USA) kits, the next-generation sequencing technology by MiSeq FGx System (Illumina, USA) was applied to further validation. To solve the inconsistent outcomes reached by the above mentioned approaches at D2S441 locus, single gene amplification, gene cloning, and genetic sequencing was also performed. As a result, five rare alleles were detected. Two novel alleles of allele 3 at the D13S317 locus and allele 5 at the D2S441 locus were found; three previously reported alleles of allele 9 at D1S1656 locus, allele 19 at Penta D locus, and allele 28 at D12S391 locus in STRBase were initially supplemented with sequence information. We, therefore, propose that such uncommon observations with rare events should be carefully investigated and interpreted.

Lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients: an integrated bioinformatic analysis.

BACKGROUND: Hyperlipidaemia is an important factor that induces coronary artery disease (CAD). This study aimed to explore the lipid metabolism patterns and relevant clinical and molecular features of coronary artery disease patients. METHODS: In the current study, datasets were fetched from the Gene Expression Omnibus (GEO) database and nonnegative matrix factorization clustering was used to establish a new CAD classification based on the gene expression profile of lipid metabolism genes. In addition, this study carried out bioinformatics analysis to explore intrinsic biological and clinical characteristics of the subgroups. RESULTS: Data for a total of 615 samples were extracted from the Gene Expression Omnibus database and were associated with clinical information. Then, this study used nonnegative matrix factorization clustering for RNA sequencing data of 581 lipid metabolism relevant genes, and the 296 patients with CAD were classified into three subgroups (NMF1, NMF2, and NMF3). Subjects in subgroup NMF2 tended to have an increased severity of CAD. The CAD index and age of group NMF1 were similar to those of group NMF3, but their intrinsic biological characteristics exhibited significant differences. In addition, weighted gene coexpression network analysis (WGCNA) was used to determine the most important modules and screen lipid metabolism related genes, followed by further analysis of the DEGs in which the significant genes were identified based on clinical information. The progression of coronary atherosclerosis may be influenced by genes such as PTGDS and DGKE. CONCLUSION: Different CAD subgroups have their own intrinsic biological characteristics, indicating that more personalized treatment should be provided to patients in each subgroup, and some lipid metabolism related genes (PDGTS, DGKE and so on) were related significantly with clinical characteristics.

Efficiency Assessment of Bacterial Cellulose on Lowering Lipid Levels In Vitro and Improving Lipid Metabolism In Vivo.

Bacterial cellulose (BC) is well known as a high-performance dietary fiber. This study investigates the adsorption capacity of BC for cholesterol, sodium cholate, unsaturated oil, and heavy metal ions in vitro. Further, a hyperlipidemia mouse model was constructed to investigate the effects of BC on lipid metabolism, antioxidant levels, and intestinal microflora. The results showed that the maximum adsorption capacities of BC for cholesterol, sodium cholate, Pb2+ and Cr6+ were 11.910, 16.149, 238.337, 1.525 and 1.809 mg/g, respectively. Additionally, BC reduced the blood lipid levels, regulated the peroxide levels, and ameliorated the liver injury in hyperlipidemia mice. Analysis of the intestinal flora revealed that BC improved the bacterial community of intestinal microflora in hyperlipidemia mice. It was found that the abundance of Bacteroidetes was increased, while the abundance of Firmicutes and Proteobacteria was decreased at the phylum level. In addition, increased abundance of Lactobacillus and decreased abundance of Lachnospiraceae and Prevotellaceae were obtained at the genus level. These changes were supposed to be beneficial to the activities of intestinal microflora. To conclude, the findings prove the role of BC in improving lipid metabolism in hyperlipidemia mice and provide a theoretical basis for the utilization of BC in functional food.

Identification of methylation-driven genes related to the prognosis of papillary renal cell carcinoma: a study based on The Cancer Genome Atlas.

BACKGROUND: Aberrant DNA methylation patterns are involved in the pathogenesis of papillary renal cell carcinoma (pRCC). This study aimed to investigate the potential of methylation-driven genes as biomarkers in determining the prognosis of pRCC by bioinformatics analysis. METHODS: DNA methylation and transcriptome profiling data were downloaded from The Cancer Genome Atlas database. Methylation-driven genes (MDGs) were obtained using MethylMix R package. A Cox regression model was used to screen for pRCC prognosis-related MDGs, and a linear risk model based on MDG methylation profiles was constructed. A combined methylation and gene expression survival analysis was performed to further explore the prognostic value of MDGs independently. RESULTS: A total of 31 MDGs were obtained. Univariate and multivariate Cox regression analysis identified eight genes (CASP1, CD68, HOXD3, HHLA2, HOXD9, HOXA10-AS, TMEM71, and PLA2G16), which were used to construct a predictive model associated with overall survival in pRCC patients. Combined DNA methylation and gene expression survival analysis revealed that C19orf33, GGT6, GIPC2, HHLA2, HOXD3, HSD17B14, PLA2G16, and TMEM71 were significantly associated with patients' survival. CONCLUSION: Through the analysis of MDGs in pRCC, this study identified potential biomarkers for precision treatment and prognosis prediction, and provided the basis for future research into the molecular mechanism of pRCC.

Validation and characterization of a QTL for adult plant resistance to stripe rust on wheat chromosome arm 6BS (Yr78).

KEY MESSAGE: This study validated one QTL for adult plant resistance to stripe rust, identified donor lines of the resistance allele, and demonstrated that it is different from previously named Yr genes. The spread of more virulent and aggressive races of Puccinia striiformis f. sp. tritici (Pst, causal pathogen of stripe rust) after the year 2000 has caused substantial yield losses worldwide. To find new sources of resistance, we previously performed a genome-wide association study and identified a strong QTL for adult plant resistance on the short arm of chromosome 6B (QYr.ucw-6B). In this study, we validated QYr.ucw-6B in ten biparental populations, and mapped it 0.6 cM proximal to IWA7257 and 3.9 cM distal to IWA4408. We showed that QYr.ucw-6B is located approximately 15 cM proximal to the all-stage resistance gene Yr35 and that none of the resistant lines carries the previously cloned Yr36 gene. Based on these results, QYr.ucw-6B was assigned the name Yr78. This gene was not effective against Pst at the seedling stage, suggesting that it is an adult plant resistance gene. Yr78 has been effective against Pst races present in field experiments performed in the Western USA between 2011 and 2016. Since this gene is predicted to be present at low frequency in wheat germplasm from this region, it can provide a useful tool to diversify the sources of resistance against this devastating pathogen.

Luminescent Strategies for Label-Free G-Quadruplex-Based Enzyme Activity Sensing.

By catalyzing highly specific and tightly controlled chemical reactions, enzymes are essential to maintaining normal cellular physiology. However, aberrant enzymatic activity can be linked to the pathogenesis of various diseases. Therefore, the unusual activity of particular enzymes can represent testable biomarkers for the diagnosis or screening of certain diseases. In recent years, G-quadruplex-based platforms have attracted wide attention for the monitoring of enzymatic activities. In this Personal Account, we discuss our group's works on the development of G-quadruplex-based sensing system for enzyme activities by using mainly iridium(III) complexes as luminescent label-free probes. These studies showcase the versatility of the G-quadruplex for developing assays for a variety of different enzymes.

Genome origin, historical hybridization and genetic differentiation in Anthosachne australasica (Triticeae; Poaceae), inferred from chloroplast rbcL, trnH-psbA and nuclear Acc1 gene sequences.

BACKGROUND AND AIMS: Anthosachne Steudel is a group of allopolyploid species that was derived from hexaploidization between the Asian StY genome Roegneria entity and the Australasia W genome Australopyrum species. Polyploidization and apomixis contribute to taxonomic complexity in Anthosachne Here, a study is presented on the phylogeny and evolutionary history of Anthosachne australasica The aims are to demonstrate the process of polyploidization events and to explore the differentiation patterns of the St genome following geographic isolation. METHODS: Chloroplast rbcL and trnH-psbA and nuclear Acc1 gene sequences of 60 Anthosachne taxa and nine Roegneria species were analysed with those of 33 diploid taxa representing 20 basic genomes in Triticeae. The phylogenetic relationships were reconstructed. A time-calibrated phylogeny was generated to estimate the evolutionary history of A. australasica Nucleotide diversity patterns were used to assess the divergence within A. australasica and between Anthosachne and its putative progenitors. KEY RESULTS: Three homoeologous copies of the Acc1 sequences from Anthosachne were grouped with the Acc1 sequences from Roegneria, Pseudoroegneria, Australopyrum, Dasypyrum and Peridictyon The chloroplast sequences of Anthosachne were clustered with those from Roegneria and Pseudoroegneria Divergence time for Anthosachne was dated to 4·66 million years ago (MYA). The level of nucleotide diversity in Australasian Anthosachne was higher than that in continental Roegneria A low level of genetic differentiation within the A. australasica complex was found. CONCLUSIONS: Anthosachne originated from historical hybridization between Australopyrum species and a Roegneria entity colonized from Asia to Australasia via South-east Asia during the late Miocene. The St lineage served as the maternal donor during the speciation of Anthosachne A contrasting pattern of population genetic structure exists in the A. australasica complex. Greater diversity in island Anthosachne compared with continental Roegneria might be associated with mutation, polyploidization, apomixis and expansion. It is reasonable to consider that A. australasica var. scabra and A. australasica var. plurinervisa should be included in the A. australasica complex.

A facile label-free aptasensor for detecting ATP based on fluorescence enhancement of poly(thymine)-templated copper nanoparticles.

A label-free fluorescence assay has been developed for sensitive and selective detection of adenosine triphosphate (ATP) by using poly(thymine) (poly T)-templated copper nanoparticles (CuNPs) as fluorescent indicator. In our design, ATP aptamer was split into two fragments, both of which were elongated with poly T strands that can be utilized as efficient template for the formation of copper nanoparticles through the reduction of copper ions by sodium ascorbate. In the presence of ATP, the two split aptamers could be dragged to form aptamer-ATP aptamer complex, which drew the poly T strands close to each other and induced a remarkable fluorescence enhancement of poly T-templated CuNPs. Thus, an elevated fluorescence enhancement of poly T-templated CuNPs was obtained with the increase in ATP concentration. Under optimized conditions, a good linear range for ATP detection was realized from 100 nM to 100 µM with a detection limit of 10.29 nM. In addition, the application of this biosensing system in complex biological matrix was demonstrated with satisfactory results. This assay provided a simple, label-free, cost-effective, and sensitive platform for the detection of ATP.

Phylogeny and differentiation of the St genome in Elymus L. sensu lato (Triticeae; Poaceae) based on one nuclear DNA and two chloroplast genes.

BACKGROUND: Hybridization and polyploidization can be major mechanisms for plant evolution and speciation. Thus, the process of polyploidization and evolutionary history of polyploids is of widespread interest. The species in Elymus L. sensu lato are allopolyploids that share a common St genome from Pseudoroegneria in different combinations with H, Y, P, and W genomes. But how the St genome evolved in the Elymus s. l. during the hybridization and polyploidization events remains unclear. We used nuclear and chloroplast DNA-based phylogenetic analyses to shed some light on this process. RESULTS: The Maximum likelihood (ML) tree based on nuclear ribosomal internal transcribed spacer region (nrITS) data showed that the Pseudoroegneria, Hordeum and Agropyron species served as the St, H and P genome diploid ancestors, respectively, for the Elymus s. l. polyploids. The ML tree for the chloroplast genes (matK and the intergenic region of trnH-psbA) suggests that the Pseudoroegneria served as the maternal donor of the St genome for Elymus s. l. Furthermore, it suggested that Pseudoroegneria species from Central Asia and Europe were more ancient than those from North America. The molecular evolution in the St genome appeared to be non-random following the polyploidy event with a departure from the equilibrium neutral model due to a genetic bottleneck caused by recent polyploidization. CONCLUSION: Our results suggest the ancient common maternal ancestral genome in Elymus s. l. is the St genome from Pseudoroegneria. The evolutionary differentiation of the St genome in Elymus s. l. after rise of this group may have multiple causes, including hybridization and polyploidization. They also suggest that E. tangutorum should be treated as C. dahurica var. tangutorum, and E. breviaristatus should be transferred into Campeiostachys. We hypothesized that the Elymus s. l. species origined in Central Asia and Europe, then spread to North America. Further study of intraspecific variation may help us evaluate our phylogenetic results in greater detail and with more certainty.

Effect of salt intake and potassium supplementation on urinary renalase and serum dopamine levels in Chinese adults.

OBJECTIVE: The aim of our study was to assess the effects of altered salt and potassium intake on urinary renalase and serum dopamine levels in humans. METHODS: Forty-two subjects (28­65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day of NaCl), a high-salt diet for an additional 7 days (18.0 g/day of NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day of NaCl + 4.5 g/day of KCl). RESULTS: Urinary renalase excretions were significantly higher during the high-salt diet intervention than during the low-salt diet. During high-potassium intake, urinary renalase excretions were not significantly different from the high-salt diet, whereas they were significantly higher than the low-salt levels. Serum dopamine levels exhibited similar trends across the interventions. Additionally, a significant positive relationship was observed between the urine renalase and serum dopamine among the different dietary interventions. Also, 24-hour urinary sodium excretion positively correlated with urine renalase and serum dopamine in the whole population. CONCLUSIONS: The present study indicates that dietary salt intake and potassium supplementation increase urinary renalase and serum dopamine levels in Chinese subjects.

Electron Lock Manipulates the Catalytic Selectivity of Nanozyme.

Nanomaterials with enzyme-mimicking functions, termed nanozymes, offer attractive opportunities for biocatalysis and biomedicine. However, manipulating nanozyme selectivity poses an insurmountable hurdle. Here, we propose the concept of an energy-governed electron lock that controls electron transfer between nanozyme and substrates to achieve selectivity manipulation of enzyme-like catalysis. An electron lock can be constructed and opened, via modulating the nanozyme's electron energy to match the energy barrier of enzymatic reactions. An iron-doped carbon dot (FeCD) nanozyme with easy-to-regulate electron energy is selected as a proof of concept. Through regulating the conduction band which dominates electron energy, activatable oxidase and selective peroxidase (POD) with substrate affinity 123-fold higher than that of natural horseradish peroxidase (HRP) is achieved. Furthermore, while maintaining selectivity, FeCDs exhibit catalytic kinetics comparable to that of HRP upon transforming photons into electrons. Superior selectivity, efficient catalysis, and undetectable biotoxicity energize FeCDs as potent targeted drugs on antibiotic-resistant bacterial abscesses. An electron lock provides a robust strategy to manipulate selectivity toward advanced nanozymes.

Molecular dynamics simulation of surfactant reducing MMP between CH4 and n-decane.

Reinjecting produced methane offers cost-efficiency and environmental benefits for enhances oil recovery. High minimum miscibility pressure (MMP) in methane-oil systems poses a challenge. To overcome this, researchers are increasingly focusing on using surfactants to reduce MMP, thus enhancing the effectiveness of methane injections for oil recovery. This study investigated the impact of pressure and temperature on the equilibrium interfacial tension of the CH4+n-decane system using molecular dynamics simulations and the vanishing interfacial tension technique. The primary goal was to assess the potential of surfactants in lowering MMP. Among four tested surfactants, ME-6 exhibited the most promise by reducing MMP by 14.10% at 373 K. Key findings include that the addition of ME-6 enriching CH4 at the interface, enhancing its solubility in n-decane, improving n-decane diffusion capacity, CH4 weakens n-decane interactions and strengthens its own interaction with n-decane. As the difference in interactions of n-decane with ME-6's ends decreases, the system trends towards a mixed phase. This research sets the stage for broader applications of mixed-phase methane injection in reservoirs, with the potential for reduced gas flaring and environmental benefits.

Machine learning-based fracturing parameter optimization for horizontal wells in Panke field shale oil.

In the process of developing tight oil and gas reservoirs, multistage fractured horizontal wells (NFHWs) can greatly increase the production rate, and the optimal design of its fracturing parameters is also an important means to further increase the production rate. Accurate production prediction is essential for the formulation of effective development strategies and development plans before and during project execution. In this study, a novel workflow incorporating machine learning (ML) and particle swarm optimization algorithms (PSO) is proposed to predict the production rate of multi-stage fractured horizontal wells in tight reservoirs and optimize the fracturing parameters. The researchers conducted 10,000 numerical simulation experiments to build a complete training and validation dataset, based on which five machine learning production prediction models were developed. As input variables for yield prediction, eight key factors affecting yield were selected. The results of the study show that among the five models, the random forest (RF) model best establishes the mapping relationship between feature variables and yield. After verifying the validity of the Random Forest-based yield prediction model, the researchers combined it with the particle swarm optimization algorithm to determine the optimal combination of fracturing parameters under the condition of maximizing the net present value. A hybrid model, called ML-PSO, is proposed to overcome the limitations of current production forecasting studies, which are difficult to maximize economic returns and optimize the fracturing scheme based on operator preferences (e.g., target NPV). The designed workflow can not only accurately and efficiently predict the production of multi-stage fractured horizontal wells in real-time, but also be used as a parameter selection tool to optimize the fracture design. This study promotes data-driven decision-making for oil and gas development, and its tight reservoir production forecasts provide the basis for accurate forecasting models for the oil and gas industry.

Phylogenetic relationships and Y genome origin in Elymus L. sensu lato (Triticeae; Poaceae) based on single-copy nuclear Acc1 and Pgk1 gene sequences.

To estimate the origin and genomic relationships of the polyploid species within Elymus L. sensu lato, two unlinked single-copy nuclear gene (Acc1 and Pgk1) sequences of eighteen tetraploids (StH and StY genomes) and fourteen hexaploids (StStH, StYP, StYH, and StYW genomes) were analyzed with those of 35 diploid taxa representing 18 basic genomes in Triticeae. Sequence and phylogenetic analysis suggested that: (1) the St, H, W, and P genomes were donated by Pseudoroegneria, Hordeum, Australopyrum, and Agropyron, respectively, while the Y genome is closely related to the Xp genome in Peridictyon sanctum; (2) different hexaploid Elymus s.l. species may derived their StY genome from different StY genome tetraploid species via independent origins; (3) due to incomplete lineage sorting and/or hybridization events, the genealogical conflict between the two gene trees suggest introgression involving some Elymus s.l. species, Pseudoroegneria, Agropyron and Aegilops/Triticum; (4) it is reasonable to recognize the StH genome species as Elymus sensu stricto, the StY genome species as Roegneria, the StYW genome species as Anthosachne, the StYH genome species as Campeiostachys, and the StYP genome species as Kengyilia. The occurrence of multiple origin and introgression could account for the rich diversity and ecological adaptation of Elymus s.l. species.

Long afterglow particle enables spectral and temporal light management to boost photosynthetic efficiency.

Herein, we develop a strategy of matched spectral and temporal light management to improve photosynthetic efficiency by co-assembling natural thylakoid membrane (TM) with artificial long afterglow particle (LAP). To be specific, LAP with excellent stability and biocompatibility possesses the capabilities of light conversion and storage, optically-matched with the absorption of TM. These favorable features permit LAP as an additional well-functioned light source of photosynthesis performed by TM. As a consequence, enhanced photosynthesis is achieved after co-assembly, compared with pure TM. Under light, the rates of electron transfer, oxygen yield and adenosine triphosphate (ATP) production in this biohybrid architecture are boosted owing to down-conversion fluorescence emission from LAP. Under dark, persistent phosphorescence emission in charged LAP facilitates continual photosynthesis of TM, while that of pure TM almost stops immediately. This proof-of-concept work opens a new route to augment the photosynthetic efficiency of green plants by utilizing precise light-managed materials.

Molecular dynamics-based analysis of the factors influencing the CO2 replacement of methane hydrate.

The benefits of large reserves, wide distribution, and high combustion energy density of natural gas hydrates are of great practical importance to alleviate the energy tension, enhance the existing energy system in China and reduce the greenhouse effect. The CO2 replacement method is a critical way to develop natural gas hydrate, while traditional experimental methods are difficult to reveal the microscopic mechanism of the replacement system. An MD (molecular dynamics) technique was utilized in this work to simulate the process of carbon dioxide replacement of gas hydrates. This simulation investigates the effects of temperature, pressure, and CO2 purity during the CO2 replacement process. CO2, different concentrations of CO2/H2O, and CO2/NH3 are used as the injected fluid. The simulation results show that the influence of temperature on the CO2 replacement of natural gas hydrate is more significant than that of pressure. Within the temperature and pressure range specified in the simulation, H2O inhibits the replacement of CO2, owing to the inhibitory effect increasing as the concentration of H2O increases; NH3 promotes the process of CO2 replacement under the temperature conditions of 250 K and 260 K, and the promotion effect becomes more significant as the concentration of NH3 increases. However, adding NH3 inhibits the CO2 replacement process with hydrate when the temperature lifts to 270 K. These findings provide new ideas to improve the efficiency of the CO2 replacement method and provide theoretical insight for the engineering exploitation of hydrates.

Analysis of Variables Associated with Positive Micro-Embolic Signals Detected by Transcranial Doppler in Patients with Atrial Fibrillation and Their Predictive Value for Embolic Risk.

Objective: This study examined the factors associated with positive micro-embolic signals (MES) on transcranial Doppler monitoring in patients with atrial fibrillation (AF), as well as the predictive value of MES for the risk of embolism in AF. Methods: Sixty-six patients who had micro emboli with AF were included in the positive group, and 75 patients who did not have micro emboli with AF served as the control group. The clinical data, congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74, female (CHA2DS2-VASc) score, D-dimer (D-d) level, echocardiography results, and brain magnetic resonance imaging (MRI) findings were compared between the two groups. Logistic regression models were used to analyze the relationship between positive micro emboli with CHA2DS2-VASc score, D-d, left atrial anteroposterior diameter (LAD), and silent cerebral ischemia (SCI) occurrence. Results: The CHA2DS2-VASc score, D-d level, and LAD were significantly higher in the positive group than in the control group (P < 0.05) and were accompanied by a higher detection rate of SCI by brain MRI (P < 0.01). Elevated D-d levels, increased LAD, and the detection rate of SCI were all highly positively correlated with positive micro emboli. Also, CHA2DS2-VASc score ≥ 2 showed a significant positive correlation with positive micro emboli, and the higher CHA2DS2-VASc score was associated with a stronger correlation. The multivariate regression analysis demonstrated that positive micro-embolic was independently associated with SCI and a CHA2DS2-VASc score of ≥ 4. Conclusion: Positive micro emboli in patients with persistent AF are consistent with an increased risk of embolism, and are independently associated with a higher CHA2DS2-VASc score and SCI, which can be used as an indicator of individual embolic risk in patients with AF.

Electroacupuncture promotes apoptosis and inhibits axonogenesis by activating p75 neurotrophin receptor for triple-negative breast xenograft in mice.

PURPOSE: The aim of this study was to investigate the anti-tumor effect of electroacupuncture (EA) on mice bearing breast tumors by regulating p75 neurotrophin receptor (p75NTR) and remodelling intratumoral innervation. METHODS: Female BALB/c mice were implanted with 4T1 breast tumor cells to establish a murine mammary cancer model. Tumor volume and weight were measured to evaluate tumor growth. Cell apoptosis was assessed by TUNEL assay. The relative expression of p75NTR, TrkA, TrkB, NGF and proNGF were detected by immunohistochemistry. Neurotransmitter and neurotrophin were detected by enzyme-linked immunosorbent assay. Intratumoral innervation was confirmed by ß3-tubulin and TH labeling immunohistochemistry. The antagonist TAT-Pep5 was employed to determine if the effects of EA on tumor growth and cell apoptosis were mediated by p75NTR. RESULTS: Peritumoral EA alleviated tumor growth especially after 14 days of intervention. Apoptosis index in the tumor tissue was obviously decreased after EA. Meanwhile, EA intervention significantly upregulated the expression of p75NTR and proNGF, along with a decline in the tumor growth and an increase in the cell apoptosis. Besides, EA reduced local sympathetic innervation and downregulated sympathetic neurotransmitter NE level in the local tumor. Furthermore, p75NTR antagonist alleviated EA-mediated cell apoptosis and intratumoral innervation. CONCLUSIONS: One mechanism of EA intervention for alleviating tumor progression is mediated by p75NTR to promote apoptosis and decrease intratumoral axonogenesis in the tumor microenvironment.