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Soil aridification and desertification are particularly prominent in China’s karst areas, severely limiting crop yields and vegetation restoration. Therefore, it is very important to identify naturally drought-tolerant plant species. Sophora davidii (Franch.) Skeels is resistant to drought and soil infertility, is deeply rooted and is an excellent plant material for soil and water conservation. We studied the transcriptomic and metabolomic changes in S. davidii in response to drought stress (CK, control; LD, mild drought stress; MD, moderate drought stress; and SD, severe drought stress). Sophora davidii grew normally under LD and MD stress but was inhibited under SD stress; the malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), soluble sugar, proline, chlorophyll a, chlorophyll b and carotenoid contents and ascorbate peroxidase (APX) activity significantly increased, while the superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and soluble protein content significantly decreased. In the LD/CK, MD/CK and SD/CK comparison groups, there were 318, 734 and 1779 DEGs, respectively, and 100, 168 and 281 differentially accumulated metabolites, respectively. Combined analysis of the transcriptomic and metabolomic data revealed the metabolic regulation of S. davidii in response to drought stress. First, key candidate genes such as PRR7 , PRR5 , GI , ELF3 , PsbQ , PsaK , INV , AMY , E2.4.1.13 , E3.2.1.2 , NCED , PP2C , PYL , ABF , WRKY33 , P5CS , PRODH , AOC3 , HPD , GPX , GST , CAT and SOD1 may govern the drought resistance of S. davidii . Second, three metabolites (oxidised glutathione, abscisic acid and phenylalanine) were found to be related to drought tolerance. Third, several key candidate genes and metabolites involved in 10 metabolic pathways were identified, indicating that these metabolic pathways play an important role in the response to drought in S. davidii and possibly other plant species.

Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients.

Sophora davidii is an important plant resource in the karst region of Southwest China, but S. davidii plant-height mutants are rarely reported. Therefore, we performed phenotypic, anatomic structural, transcriptomic and metabolomic analyses to study the mechanisms responsible for S. davidii plant-height mutants. Phenotypic and anatomical observations showed that compared to the wild type, the dwarf mutant displayed a significant decrease in plant height, while the tall mutant displayed a significant increase in plant height. The dwarf mutant cells were smaller and more densely arranged, while those of the wild type and the tall mutant were larger and loosely arranged. Transcriptomic analysis revealed that differentially expressed genes (DEGs) involved in cell wall biosynthesis, expansion, phytohormone biosynthesis, signal transduction pathways, flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched in the S. davidii plant-height mutants. Metabolomic analysis revealed 57 significantly differential metabolites screened from both the dwarf and tall mutants. A total of 8 significantly different flavonoid compounds were annotated to LIPID MAPS, and three metabolites (chlorogenic acid, kaempferol and scopoletin) were involved in phenylpropanoid biosynthesis and flavonoid biosynthesis. These results shed light on the molecular mechanisms of plant height in S. davidii mutants and provide insight for further molecular breeding programs.

Global warming has far-reaching effects on plant growth and development. As a warm-season forage grass, Paspalum wettsteinii is highly adaptable to high temperatures. However, the response mechanism of P. wettsteinii under high-temperature stress is still unclear. Therefore, we investigated the physiological indicators, transcriptome and metabolome of P. wettsteinii under different heat stress treatments. Plant height, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the contents of soluble sugar, proline, chlorophyll a , and chlorophyll b increased and then decreased, while the malondialdehyde (MDA) content decreased and then increased with increasing heat stress. Transcriptomic analysis revealed that genes related to energy and carbohydrate metabolism, heat shock proteins (HSPs), and transcription factors (TFs), secondary metabolite biosynthesis and the antioxidant system significantly changed to varying degrees. Metabolomic analysis showed that only free fatty acids were downregulated, while amino acids and their derivatives, organic acids, flavonoids, and sugars were both up- and downregulated under heat stress. These combined analyses revealed that growth was promoted at 25–40°C, while at 45°C, excess reactive oxygen species (ROS) damage reduced antioxidant and osmoregulatory effects and inactivated genes associated with the light and electron transport chains (ETCs), as well as damaged the PS II system and inhibited photosynthesis. A small number of genes and metabolites were upregulated to maintain the basic growth of P. wettsteinii . The physiological and biochemical changes in response to high-temperature stress were revealed, and the important metabolites and key genes involved in the response to high temperature were identified, providing an important reference for the physiological and molecular regulation of high-temperature stress in plants.

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children’s Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%–87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696

Non-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of death worldwide, and desperately needs effective treatments, such as cell therapy. Cardiopulmonary progenitors (CPPs) are stem cells for both heart and lung, but their repairing role in damaged heart is still unknown. Here, we obtained CPPs from E9.5 mouse embryos, maintained their stemness while expanding, and identified their characteristics by scRNA‐seq, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and differentiation assays. Moreover, we employed mouse MI model to investigate whether CPPs could repair the injured heart. Our data identified that CPPs exhibit hybrid fibroblastic, endothelial, and mesenchymal state, and they could differentiate into cell lineages within the cardiopulmonary system. Moreover, intramyocardial injection of CPPs improves cardiac function through CPPs exosomes (CPPs‐Exo) by promotion of cardiomyocytic proliferation and vascularization. To uncover the underlying mechanism, we used miRNA‐seq, bulk RNA‐seq, and bioinformatic approaches, and found the highly expressed miR‐27b‐3p in CPPs‐Exo and its target gene Sik1, which can influence the transcriptional activity of CREB1. Therefore, we postulate that CPPs facilitate cardiac repair partially through the SIK1‐CREB1 axis via exosomal miR‐27b‐3p. Our study offers a novel insight into the role of CPPs‐Exo in heart repair and highlights the potential of CPPs‐Exo as a promising therapeutic strategy for MI. CPPs improve recovery from cardiac injury in mice by their exosomes through the promotion of cardiomyocytic proliferation and vascularization partially by miR‐27b‐3p mediating the SIK1‐CREB1 axis.

Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized by the involvement of the dermis, subcutaneous tissue, and fascia. The treatment for EF usually involves long-term use of glucocorticoids and immunosuppressants. Patients with EF are at risk of developing third-degree atrioventricular (AV) block during the course of the disease. The distinctive features of EF, the side effects of its treatment, and the inherent limitations of transvenous pacemakers (TVPs) present significant challenges in the management of patients with EF who also have third-degree AV block. We present the case of a 64-year-old Chinese male diagnosed with EF and concomitant third-degree AV block. Given the patient’s skin tissue characteristics, the increased risk of infection associated with long-term immunosuppressive therapy, and the potential complications related to TVPs we chose to implant a leadless pacemaker(LP) in the apical region of the right ventricle. This case report underscores the importance of identifying potential cardiovascular complications in EF patients treated with corticosteroids and immunosuppressants. It also highlights the clinical benefit of LP implantation in managing patients with EF and third-degree AV block, especially in terms of minimizing device-related complications and infection risks. This study offers a fresh perspective on the treatment of EF patients who have third-degree AV block and advocates for the use of LPs as a preferred option for cardiac pacing in this patient group. Further research is warranted to evaluate the indications and potential benefits of LPs in a wider range of patients. Clinical trial number Not applicable.

Sophora davidii is an ideal material for studying the response to low phosphorus (P) because of its strong adaptability to low-P habitats. However, to date, there has been no research on S. davidii under low-P stress. In this paper, the differentially expressed genes (DEGs) of S. davidii were studied on days 3 and 9 of low-P treatment by transcriptome sequencing and analysed with GO and KEGG analyses. Under low-P stress, the contents of antioxidants (POD, SOD and CAT), osmotic adjusters (soluble protein and proline) and anthocyanin increased. Under low-P and normal-P conditions, 323 (209 and 114 of whose expression was upregulated and downregulated, respectively) and 504 DEGs (280 and 224 of whose expression was upregulated and downregulated, respectively) were found in S. davidii on days 3 and 9, respectively. The analysis of transcriptomics data revealed certain aspects of genes regulation under low-P stress. First, several key candidate genes, such as Orphans, GNAT, bZIP, MYB, AP2-EREBP, NAC and WRKY genes, were predicted to determine tolerance to low-P stress. Second, four pathways (starch and sucrose metabolism; plant hormone signal transduction; phenylpropanoid biosynthesis; and alanine, aspartate and glutamate metabolism) were correlated with low-P stress and were highly differentially regulated in two time treatments. These results provide new insights into the complex mechanisms of the low-P response in S. davidii or even other plant species.

Objective To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. Methods A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children’s Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group ( N  = 1950) and the non-high-quality cleavage embryo group ( N  = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group ( N  = 124) and the non-high-quality blastocyst group ( N  = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. Results Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636–0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759–0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741–0.884). Conclusion We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.