Atherosclerotic cardiovascular disease is a major cause of human disability and mortality. Our previous study demonstrated the safety and efficacy of sonodynamic therapy (SDT) on atherosclerotic ...plaques. However, traditional single-element therapeutic transducer has single acoustic field, and positioning therapeutic and imaging transducers in the same position is difficult during ultrasound imaging-guided SDT. Continuously changing the position of transducers to intervene lesions in different positions is required, increasing the difficulty of treatment. Thus, an SDT device with precise theranostics is required. Therefore, we designed and fabricated a "concentric ultrasound transducer for theranostics" (CUST-T), comprising a central 8-MHz linear array transducer for ultrasound imaging, and a peripheral 1-MHz hollow two-dimensional (2-D) planar array transducer for generating phased-array focused ultrasound (PAFUS). The CUST-T exhibited high imaging resolution at a distance of up to 20 mm from the transducer and could generate a personalized complex PAFUS acoustic field to match various lesions. In vitro biomedical results showed that PAFUS-SDT induced RAW264.7-derived foam cell apoptosis leading to a targeting field apoptotic rate 4.36-6.24 times that of the nontargeting field and the significant apoptotic region was consistent with the PAFUS acoustic field. In vivo, PAFUS-SDT guided by ultrasound imaging significantly increased the lumen area (<inline-formula> <tex-math notation="LaTeX">{P} < 0.05 </tex-math></inline-formula>) and collagen level (<inline-formula> <tex-math notation="LaTeX">{P} < 0.01 </tex-math></inline-formula>), whereas the wall thickness (<inline-formula> <tex-math notation="LaTeX">{P} < 0.05 </tex-math></inline-formula>) and lipid content (<inline-formula> <tex-math notation="LaTeX">{P} < 0.01 </tex-math></inline-formula>) of rabbit femoral artery were reduced. In conclusion, CUST-T provided image guidance sufficient for accurate SDT for atherosclerotic plaques in peripheral arteries and could be applied in clinical practice.
It has been demonstrated that reprogramming factors are sequestered in the pronuclei of zygotes after fertilization, because zygotes enucleated at the M phase instead of interphase of the first ...mitosis can support the development of cloned embryos. However, the contribution of the parental pronucleus derived from either the sperm or the oocyte in reprogramming remains elusive. Here, we demonstrate that the parental pronuclei have asymmetric reprogramming capacities and that the reprogramming factors reside predominantly in the male pronucleus. As a result, only female pronucleus-depleted (FPD) mouse zygotes can reprogram somatic cells to a pluripotent state and support the full-term development of cloned embryos; male pronucleus-depleted (MPD) zygotes fail to support somatic cell reprogramming. We further demonstrate that fusion of an additional male pronucleus into a zygote greatly enhances reprogramming efficiency. Our data provide a clue to further identify critical reprogramming factors in the male pronucleus.
A small subgroup of embryonic stem cells (ESCs) exhibit molecular features similar to those of two-cell embryos (2C). However, it remains elusive whether 2C-like cells and 2C embryos share similar ...epigenetic features. Here, we map the genome-wide profiles of histone H3K4me3 and H3K27me3 in 2C-like cells. We found that the majority of genes in 2C-like cells inherit their histone status from ESCs. Among the genes showing a switch in their histone methylation status during 2C-like transitions, only a small number acquire 2C-embryo epigenetic signatures. In contrast, broad H3K4me3 domains display extensive loss in 2C-like cells. Most of the differentially expressed genes display decreased H3K4me3 and H3K27me3 levels in 2C-like cells, whereas de novo H3K4me3 deposition is closely linked with the expression levels of upregulated 2C-specific genes. Taken together, our study reveals the unique epigenetic profiles of 2C-like cells, facilitating the further exploration of totipotency in the future.
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•2C-like embryonic stem cells (ESCs) display intermediate epigenetic profiles•Bivalent genes are preserved in 2C-like ESCs•Broad H3K4me3 domains display extensive loss in 2C-like ESCs•Highly upregulated 2C-specific genes are correlated with increased H3K4me3 levels
Le et al. show that the majority of genes in 2C-like ESCs inherit their histone status from ESCs. Among the genes showing a switch in their histone methylation status during 2C-like transitions, only a small number acquire a 2-cell-embryo epigenetic signatures.
Purpose: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer. ...Materials and Methods: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis. Results: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio HR, 2.299; 95% confidence interval CI, 1.482-3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584-3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273-3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480-3.705; P<0.001) in multivariate Cox regression analysis. Conclusions: Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.
The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) remains a threat to pregnant women. However, the impact of early ...pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood. Here, we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy. Compared to control placentas, SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection. However, subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface. Notably, the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester. Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.
Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability ...of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
In recent years, Apolygus lucorum has caused increasing damage to cotton and fruit trees in China. The salivary enzymes secreted by A. lucorum when sucking on host plants induce a series of ...biochemical reactions in plants, and the pre-oral digestion benefits the bug feeding. In this study, the food intake of A. lucorum from 1.sup.st instar nymphs to adults was measured, and the corresponding salivary activity of pectinase, amylase, cellulase, protease, polyphenol oxidase and peroxidase was determined. Daily food intake varied with developmental stage, peaking in 3.sup.rd and 4.sup.th instar nymphs. Pectinase, amylase, cellulase and protease were detected in both nymphal and adult saliva of A. lucorum, while neither polyphenol oxidase nor peroxidase was detected. Protease activity varied with food intake peaking at the 3.sup.rd -4.sup.th instar, and then slightly decreasing at the 5.sup.th instar. Levels of pectinase, amylase and cellulase increased significantly with the daily feeding level until the 3.sup.rd instar, corresponding with increasing damage to host plants. The activity of both cellulase and protease had a significant linear relationship with the average daily food intake. The increasing activity of enzymes in saliva explain stage-specific impacts of A. lucorum on the host plants, and suggest that optimal management of A. lucorum would be confined to its control threshold prior to the peak of daily feeding in the 3.sup.rd instar.
In this paper, problem of robust stability of uncertain neural networks with interval time-varying delays has been investigated. The delay factor is assumed to be time-varying and belongs to a given ...interval, which means that the lower and upper bounds of the interval time-varying delays are available. Based on the Lyapunov–Krasovskii functional approach, a new delay-dependent stability criteria is presented in terms of linear matrix inequalities (LMIs). Two numerical examples are given to illustrate the effectiveness of the proposed method.
Androgenetic haploid embryonic stem cells (AG-haESCs) hold great promise for exploring gene functions and generating gene-edited semi-cloned (SC) mice. However, the high incidence of ...self-diploidization and low efficiency of SC mouse production are major obstacles preventing widespread use of these cells. Moreover, although SC mice generation could be greatly improved by knocking out the differentially methylated regions of two imprinted genes, 50% of the SC mice did not survive into adulthood. Here, we found that the genome-wide DNA methylation level in AG-haESCs is extremely low. Subsequently, downregulation of both de novo methyltransferase Dnmt3b and other methylation-related genes was determined to be responsible for DNA hypomethylation. We further demonstrated that ectopic expression of Dnmt3b in AG-haESCs could effectively improve DNA methylation level, and the high incidence of self-diploidization could be markedly rescued. More importantly, the developmental potential of SC embryos was improved, and most SC mice could survive into adulthood.
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•Dnmt3b restores methylation of hypomethylated AG-haESCs•Dnmt3b suppresses self-diploidization of AG-haESCs•Dnmt3b promotes developmental potential of SC embryos•Dnmt3b improves SC mice survival to adulthood
Ectopic expression of Dnmt3b could rescue DNA methylation level in repetitive sequences of hypomethylated AG-haESCs, suppress high incidence of self-diploidization, and promote developmental potential of SC embryos, and most SC mice could survive into adulthood.
The gut microbiota plays an important role in animals. Metabolomics analysis was used in this study to investigate the rumen microbiota density and metabolome interactions in lambs supplemented with ...Astragalus root powder; the density of the rumen microbiota and its relationship with the metabolome in lambs supplemented with Astragalus root powder were evaluated. The results showed a significant correlation between the rumen microbiota and its metabolome in lambs. These findings have important implications for livestock nutrition and management practices, particularly in terms of improving overall productivity and profitability. The gut microbiota is highly symbiotic with the host, and the microbiota and its metabolites are essential for regulating host health and physiological functions. Astragalus, as a feed additive, can improve animal immunity. However, the effects of Astragalus root powder on the rumen microbiota and their metabolites in lambs are not apparent. In this study, thirty healthy Hu sheep lambs with similar body weights (17.42 ± 2.02 kg) were randomly selected for the feeding experiment. Lambs were fed diets supplemented with 0.3% Astragalus root powder, and the rumen microbiota density and metabolome were measured to determine the effects of Astragalus on the health of lambs in the rumen. The results showed that the relative abundance of Butyrivibrio fibrisolvens (Bf), Ruminococcus flavefaciens (Rf), Succiniclasticum (Su), and Prevotella (Pr) in the rumen was increased in the Astragalus group (p < 0.01), and metabolic profiling showed that the metabolites, such as L-lyrosine and L-leucine, were upregulated in the Astragalus group (p < 0.01). KEGG functional annotation revealed that upregulated metabolites were mainly enriched in the pathways of amino acid metabolism, lipid metabolism, fatty acid biosynthesis, and bile secretion in the Astragalus group, and downregulated metabolites were enriched in the pathways of methane metabolism and other pathways. Correlation analysis revealed that butyric acid was positively correlated with Roseburia and Blautia (p < 0.05) and negatively correlated with Desulfovibrio (p < 0.05). Thus, by analyzing the interactions of Astragalus root powder with the density of rumen microorganisms and their metabolites in lambs, it was shown that Astragalus root powder could improve the structure of rumen microbiota and their metabolites and then participate in the regulation of amino acid metabolism, lipid metabolism, immune metabolism, and other pathways to improve the efficiency of energy absorption of the lambs.
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