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Epithelial-to-mesenchymal transition (EMT) contributes significantly to chemotherapy resistance and remains a critical challenge in treating advanced breast cancer. The complexity of EMT, involving redundant pro-EMT signaling pathways and its paradox reversal process, mesenchymal-to-epithelial transition (MET), has hindered the development of effective treatments. In this study, we utilized a Tri-PyMT EMT lineage-tracing model in mice and single-cell RNA sequencing (scRNA-seq) to comprehensively analyze the EMT status of tumor cells. Our findings revealed elevated ribosome biogenesis (RiBi) during the transitioning phases of both EMT and MET processes. RiBi and its subsequent nascent protein synthesis mediated by ERK and mTOR signalings are essential for EMT/MET completion. Importantly, inhibiting excessive RiBi genetically or pharmacologically impaired the EMT/MET capability of tumor cells. Combining RiBi inhibition with chemotherapy drugs synergistically reduced metastatic outgrowth of epithelial and mesenchymal tumor cells under chemotherapies. Our study suggests that targeting the RiBi pathway presents a promising strategy for treating patients with advanced breast cancer.

Abstract Background With long-term research on the reproductive ability of Qianbei Ma goat, we found that the puberty of the male goats comes at the age of 3 months and reaches sexual maturity at 4 months,the male goats are identified as physically mature at 9 months and able to mate. Compared with other kinds of breeds of goats, Qianbei Ma goat is featured with more faster growth and earlier sexual maturity.Therefore, in order to explore the laws of growth of Qianbei Ma goat before sexual maturity(3-month-old)and after sexual maturity (9-month-old). The testicular tissue was collected to explore their changes in morphology through HE staining, the serum was collected to detect the hormone content, and the mRNA expression profile of the testis was analyzed by transcriptomics. In this way, the effect of testicular development on the reproduction of Qianbei ma goats was further analyzed. Results The results showed that the area and diameter of spermatogenic tubules were larger at 9 months than 3 months, and the number of spermatocytes, interstitial cells, spermatogonia and secondary spermatocytes in the lumen of the tubules showed a similar trend. The appearance of spermatozoa at age 3 months indicated that puberty had begun in Qianbei Ma goats. The Elasa test for testosterone, luteinizing hormone, follicle stimulating hormone and anti-Müllerian hormone showed that the levels of these hormones in the serum at age 9 months were all highly significantly different than those at age 3 months (P 1 and p value

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors.Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs).Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13–4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster.Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk.Systematic Review Registration: identifier CRD42022316577

Fluopyram is a highly effective agricultural fungicide targeting succinate dehydrogenase (SDH). Twenty-six novel amide derivatives containing azetidine were designed and synthesized with fluopyram as the lead, and their biological activities were tested. The results showed that some compounds had obvious antifungal activities against Phomopsis sp., among them, the EC50 value of compound C24 was 5.7 mg/L, which was significantly better than fluopyram (105.4 mg/L). The curative and protective activities of compound C24 on kiwi fruit infected with Phomopsis sp. were 42.2 and 52.9 %, which were better than that of fluopyram (30.4 and 35.6 %) at 200 mg/L. Moreover, compound C24 exhibited excellent inhibitory against SDH. The results of scanning electron microscopy (SEM) indicated that the mycelium of Phomopsis sp. collapsed or even ruptured after compound C24 treatment. Meanwhile, molecular docking showed that compound C24 was deeply embedded into the SDH binding pocket, and the binding model was stabilized by a cation–π interaction with Cys-40, Tyr-58 and an H-bond with Lys-455 and Asn-452. Compound C24 can provide a valuable idea to find new succinate dehydrogenase inhibitors.

With China’s electricity spot market about to enter a new stage of “official operation” and large-scale renewable energy connected to the power system, the risk of volatility in spot market prices on the wholesale side of the electricity market is becoming more prominent. To address the issue that the current retail package design of electric power retailers cannot solve the risk of spot electricity price, this paper proposes an optimization approach for retail electricity packages considering customer response., in which the demand response model of retail users and the retail package optimization model are constructed and the DDPG reinforcement learning algorithm is applied to solve the model. Finally, simulation analysis is performed based on historical data and the results show that the optimization method of electricity retail packages taking into account user response effectively mitigates the negative impact of spot electricity price fluctuations and achieves the improvement of economic efficiency; electric power retailers appropriately reduce the pricing level of retail packages to attract new user groups to bring long-term potential revenue and achieve the increase of total revenue; The DDPG reinforcement learning algorithm is used to solve the model, which has an excellent convergence utility and can achieve the dynamic decision-making of electricity retail packages continuously, thereby guiding users to respond promptly.

The bacterial communities in the rhizosphere soil of plants facilitate the cycling of nutrient elements in the rhizosphere and regulate soil fertility. By analyzing the microecological structure of rhizosphere soil surrounding wild celery, we can provide a basis for the bionic cultivation of wild celery. In this experiment, rhizosphere soil samples from various wild celery varieties in Jilin Province were used as test materials, and high-throughput sequencing was employed to analyze and compare the rhizosphere bacterial community structures of these samples. After screening and removing chimeric sequences, a total of 1,020,108 high-quality sequences were obtained. Species classification results revealed that these bacteria encompassed 60 phyla, 183 classes, 431 orders, 702 families, and 1619 genera. There were certain differences in the composition and structure of bacterial communities among different rhizosphere soil samples. According to the richness indices, the performance order among samples was Tonghua water celery > Linjiang large-leaf celery > Linjiang old mountain celery > Tonghua large-leaf celery > Jiangyuan large-leaf celery > Tonghua old mountain celery > Linjiang water celery > artificially cultivated wild large-leaf celery > Huadian large-leaf celery > Huadian small-leaf celery > Dongfeng water celery > Jiangyuan old mountain celery. Among all bacterial communities, Pseudomonadota (37.79–22.48%) had the highest relative abundance across different regions, followed by Acidobacteriota (17.97–13.51%). RDA analysis indicated that soil pH, available phosphorus, available potassium, and alkali-hydrolyzable nitrogen in the celery rhizosphere were the primary factors influencing changes in bacterial communities. Based on the experimental analysis, it was demonstrated that there were differences in rhizosphere soil bacterial community diversity and composition among Tonghua large-leaf celery, Linjiang large-leaf celery, Jiangyuan large-leaf celery, Huadian large-leaf celery, Tonghua old mountain celery, Linjiang old mountain celery, Jiangyuan old mountain celery, Tonghua water celery, Linjiang water celery, Dongfeng water celery, Huadian small-leaf celery, and artificially cultivated wild large-leaf celery in Jilin Province.

IntroductionPeripartal cows are susceptible to a negative energy balance due to inadequate nutrient intake and high energy requirements for lactation. Improving the energy metabolism of perinatal dairy cows is crucial in increasing production in dairy cows.MethodsIn this study, we investigated the impact of rumen-protected branched-chain amino acid (RPBCAA) on the production performance, energy and lipid metabolism, oxidative stress, and immune function of primiparous dairy cows using metabolomics through a single-factor experiment. Twenty healthy primiparous Holstein cows were selected based on body condition scores and expected calving date, and were randomly divided into RPBCAA (n = 10) and control (n = 10) groups. The control group received a basal diet from calving until 21 d in milk, and the RPBCAA group received the basal diet and 44.6 g/d RPLeu, 25.14 g/d RPIle, and 25.43 g/d RPVal.ResultsIn comparison to the control group, the supplementation of RPBCAA had no significant effect on milk yield and milk composition of the dairy cows. Supplementation with RPBCAA significantly increased the concentrations of insulin, insulin growth factor 1, glucagon, and growth hormones, which are indicators of energy metabolism in postpartum cows. The very low density lipoprotein, fatty acid synthase, acetyl coenzyme A carboxylase, and hormone-sensitive lipase contents of the RPBCAA group were significantly greater than that of the control group; these metrics are related to lipid metabolism. In addition, RPBCAA supplementation significantly increased serum glutathione peroxidase and immunoglobulin G concentrations and decreased malondialdehyde concentrations. Liquid chromatography–mass spectrometry (LC-MS) analysis revealed 414 serum and 430 milk metabolic features. Supplementation with RPBCAA primarily increased concentrations of amino acid and lipid metabolism pathways and upregulated the abundance of serotonin, glutamine, and phosphatidylcholines.DiscussionIn summary, adding RPBCAA to the daily ration can influence endocrine function and improve energy metabolism, regulate amino acid and lipid metabolism, mitigate oxidative stress and maintain immune function on primiparous cows in early lactation.

Objectives: To evaluate the risk factors for increased risk of venous thrombosis after arthroscopic knee surgery. Methods: PubMed, EMBASE and Cochrane Library were searched from their inception to April 4, 2023. Observational studies investigated venous thrombosis following arthroscopic knee surgery were included. The Newcastle Ottawa Scale (NOS) was used to evaluate the methodological quality of included studies. The odd ratios (ORs) and 95% confidence intervals (CIs) pertaining to each risk factor were synthesized through a random effects model by STATA 14 software. Results: The protocol this meta-analysis has been registered on PROSPERO (CRD42023410283). A total of 22 observational studies were included in the systematic review, all of which were of moderate or high methodological quality. The results of the meta-analysis revealed that several factors were significantly associated with an elevated risk of venous thrombosis following arthroscopic knee surgery. These factors included age (mean age ≥30 years) [OR = 1.08, 95%CI (1.04, 1.13), P = 0.001], overweight or obesity [OR = 1.31, 95%CI (1.13, 1.52), P＜0.001], oral contraceptive use [OR = 1.90, 95%CI (1.52, 2.37), P＜0.001], and smoking history [OR = 1.35, 95%CI (1.06, 1.71), P = 0.014]. Furthermore, the subgroup analysis indicated that patients with an average age over 50 years [OR = 3.18, 95%CI (1.17, 8.66), P = 0.001] and those who underwent surgery with a tourniquet for ≥90 min [OR = 4.79, 95%CI (1.55, 14.81), P = 0.007] were at a significantly increased risk of venous thrombosis after knee arthroscopy. Conclusion: Age, obesity, oral contraceptives, smoking history, and prolonged tourniquet use may increase the risk of venous thrombosis after arthroscopic knee surgery. The incidence of venous thrombosis after knee arthroscopy is on a downward trend, but due to its severity, increasing awareness of risk factors and implementing effective prophylaxis are important tasks for clinicians to prevent the risk of venous thrombosis after knee arthroscopy.

A phylogenetic tree can reflect the evolutionary relationships between species or gene families, and they play a critical role in modern biological research. In this review, we summarize common methods for constructing phylogenetic trees, including distance methods, maximum parsimony, maximum likelihood, Bayesian inference, and tree-integration methods (supermatrix and supertree). Here we discuss the advantages, shortcomings, and applications of each method and offer relevant codes to construct phylogenetic trees from molecular data using packages and algorithms in R. This review aims to provide comprehensive guidance and reference for researchers seeking to construct phylogenetic trees while also promoting further development and innovation in this field. By offering a clear and concise overview of the different methods available, we hope to enable researchers to select the most appropriate approach for their specific research questions and datasets.

This study sought to explore the antimicrobial activity of punicalagin against V. parahaemolyticus and its potential modes of action. V. parahaemolyticus ATCC 17802 and RIMD 2210633Sm were exposed to punicalagin, and the energy production, membrane potential, and envelope permeability, as well as the interaction with cell biomolecules, were measured using a variety of fluorescent probes combined with electrophoresis and Raman spectroscopy. Punicalagin treatment disrupted the envelope integrity and induced a decrease in intracellular ATP and pH. The uptake of 1-N-phenyl-naphtylamine (NPN) demonstrated that punicalagin weakened the outer membrane. Punicalagin damaged the cytoplasmic membrane, as indicated by the membrane depolarization and the leakage of intracellular potassium ions, proteins, and nucleic acids. Electronic microscopy observation visualized the cell damage caused by punicalagin. Further, gel electrophoresis coupled with the Raman spectrum assay revealed that punicalagin affected the protein expression of V. parahaemolyticus, and there was no effect on the integrity of genomic DNA. Therefore, the cell envelope and proteins of V. parahaemolyticus were the assailable targets of punicalagin treatment. These findings suggested that punicalagin may be promising as a natural bacteriostatic agent to control the growth of V. parahaemolyticus.

The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-α, IFN-γ, IL-4, IL-6, IL-β, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-α, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6/MyD88/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.

The food additive titanium dioxide is commonly utilized to enhance the appearance and flavor of food products. However, this substance has been linked to gastrointestinal disorders. The aim of this study was to investigate the impact of dietary exposure of titanium dioxide E171 on Listeria monocytogenes infection in mice. Mice were mainly divided into the control, LM group (L. monocytogenes infection), and E171+LM groups (E171 supplementation before L. monocytogenes infection). Pre-exposure to E171 resulted in increased bacterial counts in the liver, spleen, ileum, colon, mesenteric lymph nodes, and feces of mice after L. monocytogenes infection. Moreover, E171 exposure increased the levels of pro-inflammatory cytokines while attenuating the levels of anti-inflammatory cytokines in mice infected with L. monocytogenes. Meanwhile, mice in the E171+LM group exhibited considerably more severe colonic inflammation and worse intestinal barrier function than mice in the LM group. The 16S rRNA gene sequencing revealed a shift in the composition of the gut microbiota of mice in the E171+LM group, characterized by a decrease in the relative abundance of Firmicutes and a decrease in the Firmicutes-to-Bacteroidetes ratio. The levels of acetate, butyrate, and isobutyrate were markedly decreased within the cecum of mice in the E171+LM group in comparison to mice in the LM group. In conclusion, these results suggest that E171 exposure could exacerbate L. monocytogenes infection in mice, which may provide useful information for future risk assessment of this commonly used food additive. [ABSTRACT FROM AUTHOR]