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Imprinted in placenta and liver (IPL) gene has been identified as an imprinted gene in the mouse and human. Its sequence and imprinting status, however, have not been determined in the domestic pigs. In the present study, a 259 base pair-specific sequence for IPL gene of the domestic pig was obtained and a novel SNP, a T/C transition, was identified in IPL exon 1. The C allele of this polymorphism was found to be the predominant allele in Landrace,Yorkshire, and Duroc. The frequency of CC genotype and C allele are different in Duroc as compared with Yorkshire (P = .038 and P = .005, resp.). Variable imprinting status of this gene was observed in different developmental stages. For example, it is imprinted in 1-day old newborns (expressed from the maternal allele), but imprinting was lost in 180-day-old adult (expressed from both parental alleles). Real-time PCR analysis showed the porcine IPL gene is expressed in all tested eight organ/tissues. The expression level was significantly higher in spleen, duodenum, lung, and bladder of 180-day-old Lantang adult compared to that in 1-day-old newborns Lantang pigs (P < .05). In conclusion, the imprinting of the porcine IPL gene is developmental stage and tissue specific. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) remains a major threat to animal health and causes substantial economic losses worldwide. The nonstructural protein 11 (NSP11) of the causative agent, PRRS virus (PRRSV), contains a highly conserved nidoviral uridylate-specific endoribonuclease (NendoU) domain essential for viral replication and immune evasion. Targeting NSP11 offers a novel approach to antiviral intervention. Through in silico virtual screening followed by a fluorescence resonance energy transfer assay , we identified A8-A2 as a promising candidate that effectively inhibits NendoU activity. Molecular docking and mutational analysis revealed that A8-A2 and its analogs target the key catalytic residues His144 and Thr217 of NSP11, located within the NendoU enzyme activity loop and pocket region, respectively. A8-A2 demonstrated dose-dependent inhibition of PRRSV replication in porcine alveolar macrophages. Notably, the NendoU is conserved across PRRSV strains and other Nidoviruses, and A8-A2 exhibited antiviral activity against both type I and type II PRRSV strains, as well as the infectious bronchitis virus, a coronavirus in the order Nidovirales . Further investigations revealed that A8-A2 impedes viral replication early in infection and reverses NSP11-mediated suppression of Poly(I:C)-induced interferon production. However, this effect occurs independently of mRNA splicing inhibition. These findings indicate that A8-A2 could act as an effective antiviral agent against infections caused by diverse PRRSV strains and may serve as a broad-spectrum agent for other Nidoviruses., Importance: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses in the pig industry, and vaccination is the principal method to prevent this viral infection currently. However, vaccination often fails to provide protection against heterologous strains, highlighting the need for alternative strategies for broad protection. The nidoviral uridylate-specific endoribonuclease (NendoU) domain plays a crucial role in viral replication and evasion of host immune responses. In this study, we identified a group of new compounds with similar chemical structures that could interfere with NendoU enzyme activity. Among these compounds, A8-A2 significantly inhibited PRRSV replication in host cells with minimal cytotoxicity. Our findings provide a new direction for developing potent antiviral compounds that can offer broad protection against different PRRSV strains, thereby mitigating their impact on pig health and benefiting the husbandry industry.

Objective: To investigate the association between solid fuel use for heating, smoking, and respiratory diseases. Methods: This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases. Results: Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR ) (95% CI ) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI ) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions: The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

This study aims to broaden the morphological scope of SDH-deficient renal cell carcinoma and to assist clinicians and pathologists in better understanding this entity to prevent misdiagnosis. This study used immunohistochemistry staining and the first-generation sequencing Sanger method for gene detection. It retrospectively analysed the clinical pathology, molecular characteristics, biological behaviour, and treatment information of one case of SDH-deficient renal cell carcinoma. The patient was a 57-year-old female with right back pain for more than 20 days and had no personal or family history of kidney tumours. In addition, the tumour cells had clear boundaries in morphology, and residual normal renal tubules could be seen around them. There were also ossification and adipose tissue around the tumour centre. The tumour cells were arranged in a glandular tubular and cord-like manner. Vacuolar and eosinophilic inclusion bodies could be observed in the cytoplasm. The nucleus was regular, the chromatin distribution was fine, and there were no obvious nucleoli. They were low-grade nuclei. In addition, no atypical mitosis or necrosis could been found. Furthermore, immunohistochemistry staining showed SDHB-negative and keratin 20 -positive tumour. Meanwhile, the first-generation sequencing also pointed out the presence of SDHB gene mutations in the tumour. After 12 months of follow-up, there was no evidence of disease recurrence in the patient. SDH-deficient renal cell carcinoma is a rare tumour associated with SDH gene germline mutations, and suspected cases should undergo SDHB immunohistochemistry staining. Most SDH-deficient renal cell carcinomas have a good prognosis, but undifferentiated cases require long-term follow-up., (© 2024. The Author(s).)

Background: To investigate the clinical effects and safety of the hybrid debranching technique for patients with acute Stanford type A aortic dissection (AD)., Methods: One hundred nine patients with acute Stanford type a AD were selected and divided into observation group and control group according to the different surgical methods. Fifty-five patients in the observation group were treated with hybrid debranching, and 54 patients in the control group were treated with Sun's operation. The operation duration, clamp time, cardiopulmonary bypass duration, volume of blood transfusion, ventilator application duration, duration of stay in the intensive care unit, aortic rupture, second thoracotomy due to hemorrhage, gastrointestinal hemorrhage, stroke, paraplegia, renal failure, and all-cause mortality were recorded. Postoperative follow-up was conducted. The number of cases that underwent follow-up and the number of cases with complete thrombosis of the false aneurysm cavity detected by computed tomography angiography (CTA) was recorded., Results: The surgical success rate was 100% in both groups, and there were no cases with unplanned secondary surgery. Compared with the control group, only the difference in the volume of blood transfusion was not significantly significant between the two groups (P = 0.052), while the rest of the observation indicators were significantly lower in the observation group than in the control group (P < 0.001 for all). The proportion of cases with complete thrombosis of the false aneurysm cavity was significantly higher in the observation group than in the control group at 3 and 6 months after surgery (P < 0.05)., Conclusion: In patients with acute Stanford type A AD involving the arch, the hybrid debranching technique was safe and effective. It was recommended for patients with advanced age and a high risk of intolerance to deep hypothermic circulatory arrest., (© 2024. The Author(s).)

Axially chiral C2-arylquinoline has been successfully constructed via asymmetric heteroannulation of alkynes catalyzed by chiral phosphoric acid with high yield and high enantioselectivity. Inspired by this intriguing work, theoretical calculations have been carried out, and the detailed reaction mechanism has been elaborated, in which the whole reaction can be divided into steps including hydrogen transfer, C-N bonding, annulation reaction and the final dehydration processes. The initial hydrogen-transfer reaction has two possible pathways, while the subsequent C-N bonding process has eight possible pathways. Then, after the annulation reaction and the final dehydration processes, the major product and byproduct were formed. QTAIM and IGMH analyses were used to illustrate the role of weak intermolecular interactions in the catalytic process, and the distortion/interaction and EDA analyses provided a deeper understanding of the origin of enantioselectivity. The calculated results are consistent with the experimental results. This work would provide valuable insights into asymmetric reactions catalyzed by chiral phosphoric acid.

Dihydroflavonol 4-reductase (DFR) significantly influences the modification of flower color. To explore the role of DFR in the synthesis of strawberry anthocyanins, in this study, we downloaded the CDS sequences of the DFR gene family from the Arabidopsis genome database TAIR; the DFR family of forest strawberry was compared; then, a functional domain screen was performed using NCBI; the selected strawberry DFR genes were analyzed; and the expression characteristics of the family members were studied by qRT-PCR. The results showed that there are 57 members of the DFR gene family in strawberry, which are mainly expressed in the cytoplasm and chloroplast; most of them are hydrophilic proteins; and the secondary structure of the protein is mainly composed of α-helices and random coils. The analysis revealed that FvDFR genes mostly contain light, hormone, abiotic stress, and meristem response elements. From the results of the qRT-PCR analysis, the relative expression of each member of the FvDFR gene was significantly different, which was expressed throughout the process of fruit coloring. Most genes had the highest expression levels in the full coloring stage (S4). The expression of FvDFR30 , FvDFR54 , and FvDFR56 during the S4 period was 8, 2.4, and 2.4 times higher than during the S1 period, indicating that the DFR gene plays a key role in regulating the fruit coloration of strawberry. In the strawberry genome, 57 members of the strawberry DFR gene family were identified. The higher the DFR gene expression, the higher the anthocyanin content, and the DFR gene may be the key gene in anthocyanin synthesis. Collectively, the DFR gene is closely related to fruit coloring, which lays a foundation for further exploring the function of the DFR gene family.

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 μmol m -2 ·s -1 ; T2, 3R: 1B, 279.69 μmol m -2 ·s -1 ; T3, 7R: 1B, 211.16 μmol m -2 ·s -1 ). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO 2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Rationale: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy., Patient Concerns: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension., Diagnoses: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy., Interventions: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause., Outcomes: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm., Lessons: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Blasting vibration's effect on ground vibration is essentially an energy transfer and transformation process (Hongtao et al., 2010) [1]. In engineering, the blasting vibration duration is often used as an objective index to evaluate the blasting vibration hazard. Thus, this study on the factors influencing blasting vibration duration is essential. In this study, the blasting vibration duration prediction formula uses frequency and energy as independent parameters, which are analysed using a statistical t probability distribution. With the blasting vibration duration prediction formula, the delay time taken for the structure to reach the resonance frequency is obtained by calculating the dominant frequency of the structure. The results indicate that the frequency and energy of the blasting vibration signal are highly correlated with the duration of blasting vibration, and their introduction as independent parameters in the prediction formula can better improve the prediction accuracy. The dominant frequency should not be neglected in blasting vibration safety evaluations, and the use of blasting vibration duration prediction to calculate the dominant frequency can better avoid the resonance phenomenon in the structure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Objective: To investigate the anti-liver cancer effects and aspartic acid (Asp)-related action mechanism of Euphorbia fischeriana Steud. (Lang Du, LD)., Methods: The mice model of liver cancer was established by injection of H22 cells. After 5 days, mice were randomly divided into model group, sorafenib group (20 mg/kg), LD high-dose (LDH, 1.36 g/kg) group, LD medium-dose (LDM, 0.68 g/kg) group, and LD low-dose (LDL, 0.34 g/kg) group, 10 mice each group. Drugs were intragastrically administered to the mice once daily for 10 days, respectively. Body weight, tumor size and tumor weight were recorded. Hepatic index was calculated. Pathological changes of liver cancer tissues were evaluated by hematoxylin and eosin staining and TUNEL staining. Liquid chromatography-mass spectrometer was used to analyze different metabolites between the model and LDH groups., Results: After LD treatment, tumor weight, tumor size and hepatic index were reduced compared with the model group. Necrocytosis and karyorrhexis of tumor cells were found. Moreover, 61 differential metabolites (18 up-regulated, 43 down-regulated) were affirmed and 20 pathways of KEGG (P<0.05) were gotten. In addition, Bel-7402, HepG2 and H22 cell viabilities were significantly increased after adding Asp into the medium. And then, the cell proliferation effect induced by Asp was ameliorated by LD., Conclusion: The anti-liver cancer efficacy of LD extract was validated in H22 mice model, and inhibition of Asp level might be the underlying mechanism., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To evaluate the effect of aging on pulmonary vessels based on computed tomography (CT) quantification and analyse the correlation between quantitative pulmonary vascular volume and pulmonary function during aging., Materials and Methods: A total of 330 healthy adult volunteers, including 161 men (53 aged 20-39 years, 61 aged 40-59 years, and 47 aged ≥60 years) and 169 women (53 aged 20-39 years, 63 aged 40-59 years, and 53 aged ≥60 years) were recruited in this study. AVIEW software was used to quantitatively measure pulmonary vascular volume, including pulmonary total blood vessel volume (TBV) and small blood vessel volume with a cross-sectional area of <5 mm 2 (BV5). Pulmonary vascular volume parameters were standardised using the ratio of vascular volume to the body surface area (BSA; TBV/BSA and BV5/BSA). Subsequently, the effect of aging on the pulmonary vessels was analysed., Results: The pulmonary vascular volume parameters TBV/BSA and BV5/BSA of the whole lung, right lung, and left lung decreased significantly with increasing age (p<0.05). Additionally, TBV/BSA and BV5/BSA of the whole lung were higher in men than in women. The declining trend of pulmonary vascular volume was consistent in men and women and increased with age., Conclusions: The pulmonary vascular volume parameters, TBV/BSA and BV5/BSA, decreased with age and were weakly positively correlated with pulmonary function., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid "84K" (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Objective: To analyze the association between waist circumference (WC) and ischemic stroke (IS). Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS. Results: A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR )=1.78, 95% CI : 1.51-2.10], and the risk increased by 72% ( HR =1.72, 95% CI : 1.40-2.12) and 83% ( HR =1.83, 95% CI : 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions: The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

Long non-coding RNAs (lncRNAs) play essential roles in various biological processes, such as chromatin remodeling, post-transcriptional regulation, and epigenetic modifications. Despite their critical functions in regulating plant growth, root development, and seed dormancy, the identification of plant lncRNAs remains a challenge due to the scarcity of specific and extensively tested identification methods. Most mainstream machine learning-based methods used for plant lncRNA identification were initially developed using human or other animal datasets, and their accuracy and effectiveness in predicting plant lncRNAs have not been fully evaluated or exploited. To overcome this limitation, we retrained several models, including CPAT, PLEK, and LncFinder, using plant datasets and compared their performance with mainstream lncRNA prediction tools such as CPC2, CNCI, RNAplonc, and LncADeep. Retraining these models significantly improved their performance, and two of the retrained models, LncFinder-plant and CPAT-plant, alongside their ensemble, emerged as the most suitable tools for plant lncRNA identification. This underscores the importance of model retraining in tackling the challenges associated with plant lncRNA identification. Finally, we developed a pipeline (Plant-LncPipe) that incorporates an ensemble of the two best-performing models and covers the entire data analysis process, including reads mapping, transcript assembly, lncRNA identification, classification, and origin, for the efficient identification of lncRNAs in plants. The pipeline, Plant-LncPipe, is available at: https://github.com/xuechantian/Plant-LncRNA-pipline., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Xanthoceras sorbifolium (yellowhorn) is a woody oil plant with super stress resistance and excellent oil characteristics. The yellowhorn oil can be used as biofuel and edible oil with high nutritional and medicinal value. However, genetic studies on yellowhorn are just in the beginning, and fundamental biological questions regarding its very long-chain fatty acid (VLCFA) biosynthesis pathway remain largely unknown. In this study, we reconstructed the VLCFA biosynthesis pathway and annotated 137 genes encoding relevant enzymes. We identified four oleosin genes that package triacylglycerols (TAGs) and are specifically expressed in fruits, likely playing key roles in yellowhorn oil production. Especially, by examining time-ordered gene co-expression network (TO-GCN) constructed from fruit and leaf developments, we identified key enzymatic genes and potential regulatory transcription factors involved in VLCFA synthesis. In fruits, we further inferred a hierarchical regulatory network with MYB-related ( XS03G0296800 ) and B3 ( XS02G0057600 ) transcription factors as top-tier regulators, providing clues into factors controlling carbon flux into fatty acids. Our results offer new insights into key genes and transcriptional regulators governing fatty acid production in yellowhorn, laying the foundation for efforts to optimize oil content and fatty acid composition. Moreover, the gene expression patterns and putative regulatory relationships identified here will inform metabolic engineering and molecular breeding approaches tailored to meet biofuel and bioproduct demands., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Ma, Wang, Liu, Yan, Tian, Li, Bao, Chen, Zhao, Xiang, Jia, Nie, Guan and Mao.)

Background: Tribulus terrestris L. (TT) was initially documented in Shen-Nong-Ben-Cao-Jing and has been used for thousands of years in China as a herb to calm liver, dispel melancholy and wind, promote blood circulation, improve eyesight, and relieve itching. Moreover, it was also used to treat breast cancer in ancient China. However, the pharmacological activities of TT extract on breast cancer have received little attention., Purpose: In this study, we investigated the anti-breast cancer effects and possible mechanisms of action of this herbal drug., Methods: Network pharmacology analysis the study of network pharmacology was done to analyze the possibility of TT's anti-breast cancer effect. And then, molecular docking between TT7/TT8 and vascular endothelial growth factor receptor 2 (VEGFR2) were performed by Autodock software as well as the related protein expressions were analyzed by western blot to verify this effect. In vivo experiment: The mouse model of breast cancer was established by injection of 4T1 cells. Then drugs were intragastrically administered to the mice once daily for fourteen days. Body weight, tumor size, and tumor weight were recorded at the end of the experiment. Moreover, tumor inhibitory rate was calculated. Finally, pathological changes and apoptosis of breast cancer tissues were respectively evaluated by HE and Hoechst staining. Proteomics and metabonomics analyses: The tumor tissues were chosen to perform conjoint analysis. Firstly, differential proteins and metabolites were found. Furthermore, the functional analyses of them were analyzed by software. At the last, immunofluorescent staining of SGPP1, SPHK1 and p-SPHK1 in tumor tissue were done., Results: 12 active ingredients of TT, 127 targets of active ingredients, 15,253 targets of breast cancer, 1,225 targets of Ru yan, and 123 overlapping genes were obtained in the network pharmacology study. There was firm conjunction between TT7/TT8 and VEGFR2. Besides, tumor size and weight were markedly reduced in TT groups compared to the model group. The tumor inhibitory rate was more than 26% in TTM group. After drug treatment, many adipocytes and cracks between tumor and apoptosis were discovered. The western blot results showed that TT aqueous extract lowered the levels of VEGFR2, ERK1/2, p-ERK1/2 (Thr202, Tyr204) and Bcl2, while increasing the levels of Bax and the ratio of Bax/Bcl2. Furthermore, 495 differential proteins and 76 differential metabolites were found between TTM and model groups with the sphingolipid metabolism pathway being enriched. At last, TT treatment significantly reduced the levels of SGPP1, SPHK1 and p-SPHK1 in tumor tissue., Conclusions: In conclusion, TT demonstrates therapeutic effects in a mouse model of breast cancer, and its mechanism of action involves the regulations of sphingolipid metabolism signaling pathways. This study lends credence to the pharmacological potential of TT extract as a breast cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases ( TPSs ) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yan, Zhou, Liu, Zhao, Tian, Shi, Bao, Li, Jia, Nie, Guo, Kong, Porth and Mao.)

Quercus dentata Thunb., a dominant forest tree species in northern China, has significant ecological and ornamental value due to its adaptability and beautiful autumn coloration, with color changes from green to yellow into red resulting from the autumnal shifts in leaf pigmentation. However, the key genes and molecular regulatory mechanisms for leaf color transition remain to be investigated. First, we presented a high-quality chromosome-scale assembly for Q. dentata. This 893.54 Mb sized genome (contig N50 = 4.21 Mb, scaffold N50 = 75.55 Mb; 2n = 24) harbors 31 584 protein-coding genes. Second, our metabolome analyses uncovered pelargonidin-3-O-glucoside, cyanidin-3-O-arabinoside, and cyanidin-3-O-glucoside as the main pigments involved in leaf color transition. Third, gene co-expression further identified the MYB-bHLH-WD40 (MBW) transcription activation complex as central to anthocyanin biosynthesis regulation. Notably, transcription factor (TF) QdNAC (QD08G038820) was highly co-expressed with this MBW complex and may regulate anthocyanin accumulation and chlorophyll degradation during leaf senescence through direct interaction with another TF, QdMYB (QD01G020890), as revealed by our further protein-protein and DNA-protein interaction assays. Our high-quality genome assembly, metabolome, and transcriptome resources further enrich Quercus genomics and will facilitate upcoming exploration of ornamental values and environmental adaptability in this important genus., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis., (© 2023. The Author(s).)

Wood decay resistance (WDR) is marking the value of wood utilization. Many trees of the Lauraceae have exceptional WDR, as evidenced by their use in ancient royal palace buildings in China. However, the genetics of WDR remain elusive. Here, through comparative genomics, we revealed the unique characteristics related to the high WDR in Lauraceae trees. We present a 1.27-Gb chromosome-level assembly for Lindera megaphylla (Lauraceae). Comparative genomics integrating major groups of angiosperm revealed Lauraceae species have extensively shared gene microsynteny associated with the biosynthesis of specialized metabolites such as isoquinoline alkaloids, flavonoid, lignins and terpenoid, which play significant roles in WDR. In Lauraceae genomes, tandem and proximal duplications (TD/PD) significantly expanded the coding space of key enzymes of biosynthesis pathways related to WDR, which may enhance the decay resistance of wood by increasing the accumulation of these compounds. Among Lauraceae species, genes of WDR-related biosynthesis pathways showed remarkable expansion by TD/PD and conveyed unique and conserved motifs in their promoter and protein sequences, suggesting conserved gene collinearity, gene expansion and gene regulation supporting the high WDR. Our study thus reveals genomic profiles related to biochemical transitions among major plant groups and the genomic basis of WDR in the Lauraceae., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tian, Guo, Yan, Shi, Nie, Zhao, Bao, Li, Kong, Su, Mao and Lin.)

Early growth response 3 (Egr3) is required for embryogenesis, but little understanding is usable about its function in embryo implantation and decidualization. The present study exhibited an obvious localization of Egr3 in luminal epithelium and subluminal stroma at implantation sites. Administration of estrogen brought about a distinct gather of Egr3 mRNA in uterine luminal and glandular epithelia. Meanwhile, Egr3 was visualized in the decidua where it might facilitate the proliferation of stromal cells via Ccnd3 and accelerate stromal differentiation, testifying the significance of Egr3 in decidualization. In ovariectomized mice uteri or stromal cells, progesterone advanced the expression of Egr3 whose obstruction counteracted the inducement of stromal differentiation by progesterone. Consistently, Egr3 mediated the influence of cAMP and heparin-binding EGF-like growth factor (HB-EGF) on the differentiation program. Additionally, cAMP-protein kinase A (PKA) signaling mediated the adjustment of progesterone on Egr3. Impediment of HB-EGF antagonized the ascendance of Egr3 conferred by cAMP. In stromal cells, Egr3 activated the transcription of Hand2 whose promoter region exhibited the binding enrichment of Egr3. Activation of Hand2 relieved the weakness of stromal differentiation by Egr3 hinderance, whereas knockdown of Hand2 neutralized the guidance of Egr3 overexpression on the differentiation program. Collectively, Egr3 was identified as an important regulator of uterine decidualization through targeting Hand2 in response to progesterone/cAMP/HB-EGF pathway., (© 2022 International Federation for Cell Biology.)

Somatic cell nuclear transfer (NT) is associated with aberrant changes in epigenetic reprogramming that impede the development of embryos, particularly during zygotic genome activation. Here, we characterized epigenetic patterns of H3K4me3, H3K9me3, and H3K27me3 in mouse NT embryos up to the second cell cycle (i.e. four-celled stage) during zygotic genome activation. In vivo fertilized and parthenogenetically activated (PA) embryos served as controls. In fertilized embryos, maternal and paternal pronuclei exhibited asymmetric H3K4me3, H3K9me3, and H3K27me3 modifications, with the paternal pronucleus showing delayed epigenetic modifications. Higher levels of H3K4me3 and H3K9me3 were observed in NT and PA embryos than in fertilized embryos. However, NT embryos exhibited a lower level of H3K27me3 than PA and fertilized embryos from pronuclear stage 3 to the four-celled stage. Our finding that NT embryos exhibited aberrant H3K4me3, H3K9me3, and H3K27me3 modifications in comparison with fertilized embryos during early zygotic genome activation help to unravel the epigenetic mechanisms of methylation changes in early NT reprogramming and provide an insight into the role of histone H3 in the regulation of cell plasticity during natural reproduction and somatic cell NT.

Few incidents of ancient allopolyploidization (polyploidization by hybridization or merging diverged genomes) were previously revealed, although there is significant evidence for the accumulation of whole genome duplications (WGD) in plants. Here, we focused on Ericales, one of the largest and most diverse angiosperm orders with significant ornamental and economic value. Through integrating 24 high-quality whole genome data selected from ~ 200 Superasterids genomes/species and an algorithm of topology-based gene-tree reconciliation, we explored the evolutionary history of in Ericales with ancient complex. We unraveled the allopolyploid origin of Ericales and detected extensive lineage-specific gene loss following the polyploidization. Our study provided a new hypothesis regarding the origin of Ericales and revealed an instructive perspective of gene loss as a pervasive source of genetic variation and adaptive phenotypic diversity in Ericales., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nie, Tian, Kong, Zhao, Chen, Jiao, El-Kassaby, Porth, Yang, Zhao and Mao.)

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle . Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy , has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle , while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii . This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Objective: To analyze the association between body mass index (BMI) and coronary heart disease. Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank (CKB) in Qingdao, a total of 33 355 participants aged 30-79 years were included in the study. Cox regression analyses were performed to evaluate the association between BMI and coronary heart disease. Results: During the follow-up for an average 9.2 years, a total of 2 712 cases of ischemic heart disease (IHD) and 420 cases of major coronary events (MCE) were found. Multivariate Cox regression analysis showed that, compared with participants with normal BMI, the participants who were overweight had a 41% and 87% higher risk of IHD and MCE, the adjusted HR were 1.41 (95% CI : 1.27-1.56) and 1.87 (95% CI : 1.43-2.44), respectively. The participants who were obesity had 91% and 143% higher risk of IHD and MCE, the adjusted HR were 1.91 (95% CI : 1.72-2.13) and 2.43 (95% CI : 1.82-3.24), respectively. Conclusion: Overweight and obesity might increase the risk for IHD and MCE.

With increasing antibiotic resistance, the use of plant derived antimicrobials (PDAs) has gained momentum. Here, we investigated the toxicity of trans-cinnamaldehyde, eugenol, and carvacrol after intramuscular injection in mice. Two doses of each PDA-300 and 500 mg/kg body weight-and vehicle controls were injected into the muscle of the right hind limb of CD-1 adult mice (n = 8/treatment). Ten physical/behavioral parameters were monitored hourly for 2 h and twice daily for 4 days post-injection together with postmortem examination of leg muscles and organs. Within the first 2 days of carvacrol treatment, one male died in each dose level and a third male receiving 500 mg/kg was removed from the study. No mortality was seen with any other treatment. Among all 81 parameters examined, significant higher relative liver weights (300 and 500 mg/kg eugenol groups; P < 0.05) and relative kidney weights (300 mg/kg carvacrol group; P < 0.001) were observed. Taken together, little to mild toxicity was seen for trans-cinnamaldehyde and eugenol, respectively, while carvacrol exerted more toxicity in males. This study lays the foundation for future extensive work with large sample size, varied treatment durations, and additional treatment levels., (© 2022. The Author(s).)

In-depth genome characterization is still lacking for most of biofuel crops, especially for centromeres, which play a fundamental role during nuclear division and in the maintenance of genome stability. This study applied long-read sequencing technologies to assemble a highly contiguous genome for yellowhorn ( Xanthoceras sorbifolium ), an oil-producing tree, and conducted extensive comparative analyses to understand centromere structure and evolution, and fatty acid biosynthesis. We produced a reference-level genome of yellowhorn, ∼470 Mb in length with ∼95% of contigs anchored onto 15 chromosomes. Genome annotation identified 22,049 protein-coding genes and 65.7% of the genome sequence as repetitive elements. Long terminal repeat retrotransposons (LTR-RTs) account for ∼30% of the yellowhorn genome, which is maintained by a moderate birth rate and a low removal rate. We identified the centromeric regions on each chromosome and found enrichment of centromere-specific retrotransposons of LINE1 and Gypsy in these regions, which have evolved recently (∼0.7 MYA). We compared the genomes of three cultivars and found frequent inversions. We analyzed the transcriptomes from different tissues and identified the candidate genes involved in very-long-chain fatty acid biosynthesis and their expression profiles. Collinear block analysis showed that yellowhorn shared the gamma (γ) hexaploidy event with Vitis vinifera but did not undergo any further whole-genome duplication. This study provides excellent genomic resources for understanding centromere structure and evolution and for functional studies in this important oil-producing plant., Competing Interests: The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yan, Wang, Zhang, Zhou, Shi, Jia, Tian, Zhou, Zhang, Yun, Wang, Xiang, Mannapperuma, Van Zalen, Street, Porth, El-Kassaby, Zhao, Wang, Guan and Mao.)

Regulation of the mammalian embryo involves cell-signaling molecules produced by the maternal oviduct and endometrium. Here, datasets on the transcriptome of the gestational Days 5 and 6 bovine morula and Day 5 maternal endometrium were examined to identify receptor genes expressed by the morula and expression of the corresponding ligand-related genes in the endometrium. A total of 175 receptor genes were identified in the morula, including 48 encoding for growth factors or WNT signaling molecules, 25 for cytokines and chemokines, 35 involved in juxtacrine and matricellular signaling and 25 encoding for receptors for small molecules. Some of the highly-expressed pairs of endometrial ligand and embryo receptor genes included MDK and its receptors ITGB1, SDC4 and LRP2, WNT5A (RYK), VEGFA (ITGB1), GPI (AMFR), and the hedgehog proteins IHH and DHH (HHIP). The most highly expressed receptors for small molecules were GPRC5C (retinoic acid receptor), PGRMC1 (progesterone), and CHRNB2 (acetylcholine). There were also 84 genes encoding for cell signaling ligands expressed by the morula, with the most highly expressed being GPI, AIMP1, TIMP1, IK, and CCN2. The atlas of receptor and ligand genes should prove useful for understanding details of the communication between the embryo and mother that underlies optimal embryonic development., (© 2021 The Authors. Molecular Reproduction and Development published by Wiley Periodicals LLC.)

Pluripotent stem cells (PSCs) have been successfully developed in many species. However, the establishment of bovine-induced pluripotent stem cells (biPSCs) has been challenging. Here we report the generation of biPSCs from bovine mesenchymal stem cells (bMSCs) by overexpression of lysine-specific demethylase 4A (KDM4A) and the other reprogramming factors OCT4, SOX2, KLF4, cMYC, LIN28, and NANOG (K d OSKMLN). These biPSCs exhibited silenced transgene expression at passage 10, and had prolonged self-renewal capacity for over 70 passages. The biPSCs have flat, primed-like PSC colony morphology in combined media of knockout serum replacement (KSR) and mTeSR, but switched to dome-shaped, naïve-like PSC colony morphology in mTeSR medium and 2i/LIF with single cell colonization capacity. These cells have comparable proliferation rate to the reported primed- or naïve-state human PSCs, with three-germ layer differentiation capacity and normal karyotype. Transcriptome analysis revealed a high similarity of biPSCs to reported bovine embryonic stem cells (ESCs) and embryos. The naïve-like biPSCs can be incorporated into mouse embryos, with the extended capacity of integration into extra-embryonic tissues. Finally, at least 24.5% cloning efficiency could be obtained in nuclear transfer (NT) experiment using late passage biPSCs as nuclear donors. Our report represents a significant advance in the establishment of bovine PSCs.

Polyploidization plays a key role in plant evolution, but the forces driving the fate of homoeologs in polyploid genomes, i.e., paralogs resulting from a whole-genome duplication (WGD) event, remain to be elucidated. Here, we present a chromosome-scale genome assembly of tetraploid scarlet sage (Salvia splendens), one of the most diverse ornamental plants. We found evidence for three WGD events following an older WGD event shared by most eudicots (the γ event). A comprehensive, spatiotemporal, genome-wide analysis of homoeologs from the most recent WGD unveiled expression asymmetries, which could be associated with genomic rearrangements, transposable element proximity discrepancies, coding sequence variation, selection pressure, and transcription factor binding site differences. The observed differences between homoeologs may reflect the first step toward sub- and/or neofunctionalization. This assembly provides a powerful tool for understanding WGD and gene and genome evolution and is useful in developing functional genomics and genetic engineering strategies for scarlet sage and other Lamiaceae species., (© 2021. The Author(s).)

Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger., (© 2021. The Author(s).)

The complete mitochondrial genome of a predominant parasitoid, Necremnus tutae (Hymenoptera: Eulophidae) (GenBank accession number MT916846) is 15,252 bp in length, and contains 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes, and an A + T-rich region. The overall base composition is 38.86% for A, 7.14% for C, 8.57% for G, and 45.43% for T, with a high AT bias of 84.29%. ATA, ATT, ATG were initiation codons and TAA and T were termination codons. All the 22 tRNAs displayed a typical cloverleaf secondary structure, except for trnS 1 and trnR which lacked the dihydrouracil (DHU) arm. Phylogenetic analyses were performed using 13 PCGs showed that N. tutae is closely related to Tenthredo tienmushana , which in accordance with the traditional classification., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Azaleas (Ericaceae) comprise one of the most diverse ornamental plants, renowned for their cultural and economic importance. We present a chromosome-scale genome assembly for Rhododendron simsii, the primary ancestor of azalea cultivars. Genome analyses unveil the remnants of an ancient whole-genome duplication preceding the radiation of most Ericaceae, likely contributing to the genomic architecture of flowering time. Small-scale gene duplications contribute to the expansion of gene families involved in azalea pigment biosynthesis. We reconstruct entire metabolic pathways for anthocyanins and carotenoids and their potential regulatory networks by detailed analysis of time-ordered gene co-expression networks. MYB, bHLH, and WD40 transcription factors may collectively regulate anthocyanin accumulation in R. simsii, particularly at the initial stages of flower coloration, and with WRKY transcription factors controlling progressive flower coloring at later stages. This work provides a cornerstone for understanding the underlying genetics governing flower timing and coloration and could accelerate selective breeding in azalea.