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Florets are the basic structural units of spikelets, and their morphogenesis determines the yield and quality of rice grains. However, whether and how pseudouridine-5′-phosphate glycosidase participates in rice spikelet development remains an open question. In this study, we identified a novel gene, OsPPG, which encodes a peroxisome-localized pseudouridine-5′-phosphate glycosidase and regulates the development of rice spikelets. osppg mutants exhibited abnormal sterile lemma, lemma, palea, lodicule, stamens, and pistils; male sterility; shorter panicles; and reduced plant height. OsPPG was found to regulate several OsMADS genes, thereby affecting the morphogenesis of rice spikelets. Furthermore, metabolomics revealed that the OsPPG gene was involved in the decomposition of pseudouridine via the pyrimidine metabolism pathway and may affect the jasmonic acid signaling pathway. These results suggest that OsPPG is a key regulator of rice spikelet development.

Introduction: The integrity of the erythrocyte membrane cytoskeletal network controls the morphology, specific surface area, material exchange, and state of erythrocytes in the blood circulation. The antioxidant properties of resveratrol have been reported, but studies on the effect of resveratrol on the hypoxia-induced mechanical properties of erythrocytes are rare.Methods: In this study, the effects of different concentrations of resveratrol on the protection of red blood cell mor-phology and changes in intracellular redox levels were examined to select an appropriate concentration for further study. The Young’s modulus and surface roughness of the red blood cells and blood viscosity were measured via atomic force microsco-py and a blood rheometer, respectively. Flow cytometry, free hemoglobin levels, and membrane lipid peroxidation levels were used to characterize cell membrane damage in the presence and absence of resveratrol after hypoxia. The effects of oxida-tive stress on the erythrocyte membrane proteins band 3 and spectrin were further investigated by immunofluorescent label-ing and Western blotting.Results and discussion: Resveratrol changed the surface roughness and Young’s modulus of the erythrocyte mem-brane, reduced the rate of eryptosis in erythrocytes after hypoxia, and stabilized the intracellular redox level. Further data showed that resveratrol protected the erythrocyte membrane proteins band 3 and spectrin. Moreover, resistance to band 3 pro-tein tyrosine phosphorylation and sulfhydryl oxidation can protect the stability of the erythrocyte membrane skeleton net-work, thereby protecting erythrocyte deformability under hypoxia. The results of the present study may provide new insights into the roles of resveratrol in the prevention of hypoxia and as an antioxidant.

(1) Background: Functional magnetic resonance imaging (fMRI) utilizing multi-echo gradient echo-planar imaging (ME-GE-EPI) has demonstrated higher sensitivity and stability compared to utilizing single-echo gradient echo-planar imaging (SE-GE-EPI). The direct derivation of T2* maps from fitting multi-echo data enables accurate recording of dynamic functional changes in the brain, exhibiting higher sensitivity than echo combination maps. However, the widely employed voxel-wise log-linear fitting is susceptible to inevitable noise accumulation during image acquisition. (2) Methods: This work introduced a synthetic data-driven deep learning (SD-DL) method to obtain T2* maps for multi-echo (ME) fMRI analysis. (3) Results: The experimental results showed the efficient enhancement of the temporal signal-to-noise ratio (tSNR), improved task-based blood oxygen level-dependent (BOLD) percentage signal change, and enhanced performance in multi-echo independent component analysis (MEICA) using the proposed method. (4) Conclusion: T2* maps derived from ME-fMRI data using the proposed SD-DL method exhibit enhanced BOLD sensitivity in comparison to T2* maps derived from the LLF method.

Introduction: Circadian clocks coordinate internal physiology and external environmental factors to regulate cereals flowering, which is critical for reproductive growth and optimal yield determination. Objectives: In this study, we aimed to confirm the role of OsLUX in flowering time regulation in rice. Further research illustrates how the OsELF4s–OsELF3-1–OsLUX complex directly regulates flowering-related genes to mediate rice heading. Methods: We identified a circadian gene OsLUX by the MutMap method. The transcription levels of flowering-related genes were evaluated in WT and oslux mutants. OsLUX forms OsEC (OsELF4s–OsELF3-1–OsLUX) complex were supported by yeast two-hybrid, pull down, BiFC, and luciferase complementation assays (LCA). The EMSA, Chip-qPCR, luciferase luminescence images, and relative LUC activity assays were performed to examine the targeted regulation of flowering genes by the OsEC (OsELF4s–OsELF3-1–OsLUX) complex. Results: The circadian gene OsLUX encodes an MYB family transcription factor that functions as a vital circadian clock regulator and controls rice heading. Defect in OsLUX causes an extremely late heading phenotype under natural long-day and short-day conditions, and the function was further confirmed through genetic complementation, overexpression, and CRISPR/Cas9 knockout. OsLUX forms the OsEC (OsELF4s–OsELF3-1–OsLUX) complex by recruiting OsELF3-1 and OsELF4s, which were required to regulate rice heading. OsELF3-1 contributes to the translocation of OsLUX to the nucleus, and a compromised flowering phenotype results upon mutation of any component of the OsEC complex. The OsEC complex directly represses Hd1 and Ghd7 expression via binding to their promoter's LBS (LUX binding site) element. Conclusion: Our findings show that the circadian gene OsLUX regulates rice heading by directly regulating rhythm oscillation and core flowering-time-related genes. We uncovered a mechanism by which the OsEC target suppresses the expression of Hd1 and Ghd7 directly to modulate photoperiodic flowering in rice. The OsEC (OsELF4s–OsELF3-1–OsLUX)–Hd1/Ghd7 regulatory module provides the genetic targets for crop improvement.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain’s intrinsic connectivity and capture dynamic changes in the brain. In this study, the hidden Markov model (HMM) and dynamic graph (DG) theory are used to study the spatial-temporal characteristics and dynamics of brain networks based on dynamic functional connectivity (DFC). By using HMM, we identified three typical brain states for ASD and healthy control (HC). Furthermore, we explored the correlation between HMM time-varying properties and clinical autism scale scores. Differences in brain topological characteristics and dynamics between ASD and HC were compared by DG analysis. The experimental results indicate that ASD is more inclined to enter a strongly connected HMM brain state, leading to the isolation of brain networks and alterations in the topological characteristics of brain networks, such as default mode network (DMN), ventral attention network (VAN), and visual network (VN). This work suggests that using different data-driven methods based on DFC to study brain network dynamics would have better information complementarity, which can provide a new direction for the extraction of neuro-biomarkers in the early diagnosis of ASD.

Abstract Early diagnosis of gastrointestinal malignancies in patients with acute coronary syndrome (ACS) is often delayed. The present study aims to demonstrate the value of [68Ga]Ga‐FAPI‐04 PET imaging in ACS with suspected gastrointestinal malignancies. Twelve ACS patients with suspected gastrointestinal malignancies were enrolled, including ST‐elevation myocardial infarction (STEMI) (n = 5), non‐ST‐elevation myocardial infarction (NSTEMI) (n = 5), and unstable angina (UA) (n = 2). All patients underwent coronary angiography (CAG) and [68Ga]Ga‐FAPI‐04 PET/MR or PET/CT within 1 week. All five STEMI and five NSTEMI patients had high [68Ga]Ga‐FAPI‐04 uptake in the injured myocardium compared to remote area (TBR: 2.10 ± 0.72 vs. 0.62 ± 013; p < .001), correlated with peak cTnI level (R = .82, p = .004). No [68Ga]Ga‐FAPI‐04 in the myocardium was found in UA patients. NSTEMI displayed a similar myocardial [68Ga]Ga‐FAPI‐04 intensity as STEMI (p = .42). Compared with STEMI, NSTEMI patients had a significantly delayed door‐to‐balloon time for reperfusion treatment (p = .023). High uptake of [68Ga]Ga‐FAPI‐04 in the gastrointestinal tract was detected in three patients. Because of no myocardial [68Ga]Ga‐FAPI‐04 expression, they discontinued antiplatelet therapy and underwent endoscopy. The rectal, colon, and gastric cancer diagnoses were made by biopsy. The other nine patients showed no accumulation of [68Ga]Ga‐FAPI‐04 beyond the heart, and invasive tumor examinations were delayed. During a median 6‐month follow‐up, no tumor formation was observed. [68Ga]Ga‐FAPI‐04 PET imaging is valuable to assess injured myocardium, detect tumors, and guide invasive examinations in ACS patients with suspected gastrointestinal malignancies.

Many excellent genes in wild rice have been lost during the domestication of wild rice to cultivated rice. In this study, introgression lines (ILs) were produced with a wild rice (Oryza rufipogon) accession, BJ194, as a donor parent and an indica restorer line, Zhonghui 8015 (ZH8015), as a recipient parent to map QTLs for plant height. We identified four QTLs (qPH3.1, qPH3.2, qPH2, and qPH8) related to plant height distributed on chromosomes 2, 3 and 8. Furthermore, we sequenced and analyzed qPH3.2 located in the interval of RM15753–RM3525, and found this QTL may be a new locus regulating rice plant height.

Abstract Background Osteoarthritis (OA) is a chronic degenerative joint disease. Extracellular matrix (ECM) degradation is essential for OA progression. Previous studies have shown that circular RNAs (circRNAs) are involved in the pathological process of OA. CircPRKCH has been shown to be upregulated in OA chondrocytes. The present study was aimed to explore the roles of circPRKCH in vivo and in vitro models of OA and its underlying molecular mechanisms. Methods IL-1β-induced chondrocytes and mice injected with monosodium iodoacetate were used as OA models in vitro and in vivo, respectively. RT-qPCR was performed to measure the expression of circPRKCH, miR-145, and HGF in cartilage tissues and chondrocytes. The interaction between miR-145 and circPRKCH or HGF was verified by a dual-luciferase reporter assay. Chondrocyte apoptosis, viability, and ECM-related proteins were examined by flow cytometry, MTT assay, and Western blotting, respectively. Histopathological changes were detected by HE and Safranin O-fast green staining. Results The expression of circPRKCH and HGF was increased in OA cartilage tissues and IL-1β-treated chondrocytes, while miR-145 expression was decreased. IL-1β induced chondrocyte apoptosis and ECM degradation in chondrocytes. Moreover, circPRKCH promoted HGF expression and activated HGF/c-MET by directly binding to miR-145. miR-145 knockdown or HGF overexpression significantly reversed circPRKCH knockdown-mediated inhibition of apoptosis and ECM degradation in IL-1β-induced chondrocytes. Besides, miR-145 overexpression alleviated IL-1β-induced chondrocyte apoptosis and ECM degradation by inhibiting HGF/c-MET. Finally, circPRKCH knockdown reduced ECM degradation by regulating the miR-145/HGF axis in an experimental OA model in mice. Conclusion Our study demonstrated that circPRKCH promoted chondrocyte apoptosis and ECM degradation via the miR-145/HGF axis in OA, which may provide a novel target for OA treatment.

Objective To evaluate the perioperative administration of dexamethasone to prevent postoperative shivering. Methods We searched PubMed, Embase, Google Scholar, Web of Science, and Cochrane Library for relevant studies of the administration of dexamethasone to prevent postoperative shivering published through 31 May 2023. The primary outcome was the incidence of postoperative shivering. Secondary outcomes comprised the incidence of postoperative nausea, vomiting, and postoperative nausea and vomiting (PONV). RevMan 5.3 software was used for the data analysis. Results We included 12 randomized controlled trials (1276 participants). The results revealed a benefit favoring the perioperative administration of dexamethasone to prevent postoperative shivering (relative risk [RR]: 0.39; 95% confidence interval [CI]: 0.23–0.63), as well as the grade of shivering. The administration of dexamethasone also reduced the incidence of postoperative nausea (RR: 0.54; 95% CI: 0.39–0.73), postoperative vomiting (RR: 0.37; 95% CI: 0.20–0.65), and PONV (RR: 0.50; 95% CI: 0.26–0.95) compared with the control group. Conclusion This study indicated that perioperative administration of dexamethasone prevented postoperative shivering and decreased the incidence of other complications. PROSPERO registration number: CRD42020164488.

Heading date (flowering time) determines the adaptability of cultivars to different environments. We report the fine mapping and candidate gene analysis of qHD1b, a quantitative trait locus (QTL) responsible for early flowering that was derived from common wild rice (O. rufipogon) under both short-day and long-day conditions. The introgression line IL7391, which carried segments from common wild rice in a Zhonghui 8015 (ZH8015) background, exhibited early heading compared to the background and was crossed with ZH8015 to generate BC5F2:3 families for QTL analysis. This enabled the identification of two heading-date QTL, named qHD1b and qHD7, of which the first was selected for further research. High-resolution linkage analysis was performed in BC5F4:5 and BC5F6 populations, and the location of qHD1b was confined to a 112.7-kb interval containing 17 predicted genes. Five of these genes contained polymorphisms in the promoter or coding regions and were thus considered as candidates. Expression analysis revealed a positive association between LOC_Os01g11940 expression and early heading. This locus was annotated as OsFTL1, which encodes an ortholog of Arabidopsis Flowering Locus T and was the most likely candidate gene for qHD1b. Our study revealed that qHD1b acts as a floral activator that promotes flowering by up-regulating Ehd1, Hd3a, RFT1, OsMADS14, and OsMADS15 under both short-day and long-day conditions. Field experiments showed that qHD1b affected several yield-related agronomic traits including 1000-grain weight and grain length. qHD1b could be useful for marker-assisted selection and breeding of early-maturing cultivars.

Abstract Background Long-term domestication and intensive breeding of crop plants aim to establish traits desirable for human needs, and characteristics related to yield, disease resistance, and postharvest storage have traditionally received considerable attention. These processes have led also to negative consequences, as is the case of loss of variants controlling fruit quality, for instance in tomato. Tomato fruit quality is directly associated to metabolite content profiles; however, a full understanding of the genetics affecting metabolite content during tomato domestication and improvement has not been reached due to limitations of the single detection methods previously employed. Here, we aim to reach a broad understanding of changes in metabolite content using a genome-wide association study (GWAS) with eigenvector decomposition (EigenGWAS) on tomato accessions. Results An EigenGWAS was performed on 331 tomato accessions using the first eigenvector generated from the genomic data as a “phenotype” to understand the changes in fruit metabolite content during breeding. Two independent gene sets were identified that affected fruit metabolites during domestication and improvement in consumer-preferred tomatoes. Furthermore, 57 candidate genes related to polyphenol and polyamine biosynthesis were discovered, and a major candidate gene chlorogenate: glucarate caffeoyltransferase (SlCGT) was identified, which affected the quality and diseases resistance of tomato fruit, revealing the domestication mechanism of polyphenols. Conclusions We identified gene sets that contributed to consumer liking during domestication and improvement of tomato. Our study reports novel evidence of selective sweeps and key metabolites controlled by multiple genes, increasing our understanding of the mechanisms of metabolites variation during those processes. It also supports a polygenic selection model for the application of tomato breeding.

Abstract Background Cucumber is an important melon crop in the world, with different pericarp colors. However, the candidate genes and the underlying genetic mechanism for such an important trait in cucumber are unknown. In this study, a locus controlling pericarp color was found on chromosome 3 of cucumber genome. Results In this study, the light green inbred line G35 and the dark green inbred line Q51 were crossed to produce one F2 population. Consequently, we identified a major locus CsPC1 (Pericarp color 1). Next, we mapped the CsPC1 locus to a 94-kb region chromosome 3 which contains 15 genes. Among these genes, Csa3G912920, which encodes a GATA transcription factor, was expressed at a higher level in the pericarp of the NIL-1334 line (with light-green pericarp) than in that of the NIL-1325 line (with dark-green pericarp). This study provides a new allele for the improvement of cucumber pericarp color. Conclusion A major QTL that controls pericarp color in cucumber, CsPC1, was identified in a 94-kb region that harbors the strong candidate gene CsGATA1.

Abstract Background Genetic and functional genomics studies require a high-quality genome assembly. Tomato (Solanum lycopersicum), an important horticultural crop, is an ideal model species for the study of fruit development. Results Here, we assembled an updated reference genome of S. lycopersicum cv. Heinz 1706 that was 799.09 Mb in length, containing 34,384 predicted protein-coding genes and 65.66% repetitive sequences. By comparing the genomes of S. lycopersicum and S. pimpinellifolium LA2093, we found a large number of genomic fragments probably associated with human selection, which may have had crucial roles in the domestication of tomato. We also used a recombinant inbred line (RIL) population to generate a high-density genetic map with high resolution and accuracy. Using these resources, we identified a number of candidate genes that were likely to be related to important agronomic traits in tomato. Conclusion Our results offer opportunities for understanding the evolution of the tomato genome and will facilitate the study of genetic mechanisms in tomato biology.

Abstract Background Chondrogenic differentiation of human adipose-derived stem cells (hADSCs) is important for cartilage generation and degradation. LncRNAs play an essential role in stem cell differentiation. However, the role and mechanism of lncRNA in hADSCs remain unclear. Our previous study showed that miR-490-5p was downregulated during chondrogenic differentiation of hADSCs. In this study, we investigated the effect and mechanism of lncRNA NONHSAT030515 interacting with miR-490-5p on chondrogenic differentiation of hADSCs. Methods Alcian blue staining was used to assess the deposition of chondromatrix proteins following chondrogenic differentiation of human adipose stem cells. Immunohistochemistry was used to evaluate the expression of collagenII. TargetScan, miRTarBase and miRDB database analyses were applied to find the miRNA and target genes of lncRNA NONHSAT030515. A dual luciferase experiment was conducted to identify the direct target of NONHSAT030515. pcDNA3.1- NONHSAT030515 transfection and sh- NONHSAT030515 treatment were conducted to verify the role of lncRNA NONHSAT030515 in chondrogenic differentiation. The levels of Aggrecan, SOX9 and COL2A1 were analyzed by qRT-PCR and Western blot assay. Results Alcian blue staining, immunocytochemical, qRT-PCR, and Western blot have determined that lncRNA NONHSAT030515 can promote the chondrogenic differentiation of hADSCs. MiR-490- 5p was the direct target of NONHSAT030515, while BMPR2 was the target gene. This result was confirmed by luciferase reporter assay. Up-regulation of NONHSAT030515 promoted BMPR2 protein expression and promoted chondrogenic differentiation, whereas down-regulation of NONHSAT030515 caused completely opposite results. Conclusion LncRNA NONHSAT030515 promotes the chondrogenic differentiation of hADSCs through increasing BMPR2 expression by regulating miR-490- 5p.

Multi-parametric quantitative magnetic resonance imaging (mqMRI) allows the characterization of multiple tissue properties non-invasively and has shown great potential to enhance the sensitivity of MRI measurements. However, real-time mqMRI during dynamic physiological processes or general motions remains challenging. To overcome this bottleneck, we propose a novel mqMRI technique based on multiple overlapping-echo detachment (MOLED) imaging, termed MQMOLED, to enable mqMRI in a single shot. In the data acquisition of MQMOLED, multiple MR echo signals with different multi-parametric weightings and phase modulations are generated and acquired in the same k-space. The k-space data is Fourier transformed and fed into a well-trained neural network for the reconstruction of multi-parametric maps. We demonstrated the accuracy and repeatability of MQMOLED in simultaneous mapping apparent proton density (APD) and any two parameters among T2, T2*, and apparent diffusion coefficient (ADC) in 130–170 ms. The abundant information delivered by the multiple overlapping-echo signals in MQMOLED makes the technique potentially robust to system imperfections, such as inhomogeneity of static magnetic field or radiofrequency field. Benefitting from the single-shot feature, MQMOLED exhibits a strong motion tolerance to the continuous movements of subjects. For the first time, it captured the synchronous changes of ADC, T2, and T1-weighted APD in contrast-enhanced perfusion imaging on patients with brain tumors, providing additional information about vascular density to the hemodynamic parametric maps. We expect that MQMOLED would promote the development of mqMRI technology and greatly benefit the applications of mqMRI, including therapeutics and analysis of metabolic/functional processes.

ObjectiveNowadays, cancer is still a leading public health problem all over the world. Several studies have reported the GPX8 could be correlated with the poor prognostic of Gastric Cancer and Breast Cancer. However, the prognostic potential of GPX8 in pan-cancer remains unclear. In this work, we aimed to explore the prognostic and immunological role of GPX8 in human cancer and confirm the oncogenic value in GBM.MethodsThe data of TCGA, CPTAC and GEO databases were adopted for the survival analysis. Based on the RNAseq and Methylation450 data of TCGA, the R language and package “ggplot2” were used to analyze the DNA methylation at the region of the promoter of GPX8 in tumors. The genetic alteration of GPX8 from TCGA cancers was investigated in cBioPortal. The R package “GSVA” and “ssGSEA” were employed to evaluate the correlation of GPX8 expression with the immune infiltration. The KEGG website was used for pathway analysis. The STRING website and GEPIA were performed to predict GPX8-binding proteins. The R package “ggplot2” and “clusterprofile” were used to analyze and visualize the GO and KEGG analysis. A normal human astrocyte cell line and three GBM cell lines were cultured under suitable conditions. The shRNA was transferred to cells by Lipofectamine 3000. The qRT-PCR and WB were adopted to detect the expression of GPX8. The wound-healing assay and transwell assay were taken to analyze the invasive and metastatic abilities. The tumor tissues and paracancerous ones were collected from patients with GBM. WB assay was employed to analyze the expression of GPX8 protein.ResultsGPX8 was a valuable diagnostic biomarker in multiple cancers, including GBM/LGG (glioblastoma multiforme/Brain lower grade glioma), KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma) and STAD (stomach adenocarcinoma). Moreover, we observed a correlation between the expression of GPX8 and the reduced DNA methylation at the promoter region in several tumors, such as GBM/LGG. Our results indicated a positive correlation between the GPX8 expression and immune infiltration. In addition, the enrichment analysis demonstrated that antioxidant activity was mainly involved in the functional mechanism of GPX8. In particular, we first confirmed the up-regulated of GPX8 in GBM cells and observed the suppression of migrative and invasive phenotypes by knockdown of GPX8. Furthermore, we confirmed the expression of GPX8 was higher in GBM tumor tissues than paracancerous ones.ConclusionOur study showed a correlation of GPX8 expression with clinical prognosis, DNA methylation and immune infiltrates. Furthermore, we first confirmed GPX8 was highly expressed in GBM cells and contributed to migration and invasion. These results provided a predictive biomarker and an inclusive understanding of the GPX8 expression in multiple tumors types, especially in GBM.

Coronary atherosclerosis (CA) is a chronic and evolving inflammatory disease characterized by the build-up of atherosclerotic plaque in the wall of coronary arteries. Guanxinning tablet (GXNT) is a novel Chinese medicine formula, which has been clinically used to treat coronary heart disease for many years. However, the potential mechanism for treating CA remains unclear. Thus, the study was aimed at investigating the therapeutic effect of GXNT on CA and further explore the underlying mechanisms from the perspective of gut microbiota. Following the establishment of a CA model in Tibetan minipigs, GXNT was orally administrated. We simultaneously detected blood lipid levels, observed ventricular function using ultrasound examination, measured platelet aggregation, and checked changes in inflammatory factors, oxidative stress factors, and vascular endothelial injury-related indexes applying ELISA assays. Histopathological changes of coronary artery tissue were subsequently evaluated using Sudan IV staining, HE staining, Oil red “O” staining, and immunohistochemistry assays. Finally, alterations of the gut microbiota and microbial metabolites were detected using metagenomic sequencing and targeted metabolomics, respectively. The results have suggested that GXNT could regulate dyslipidemia, improve heart function, and inhibit the levels of ox-LDL, CRP, TNF-α, IL-1β, SOD, MDA, vWF, and ET-1, as well as platelet aggregation. Additionally, histopathological findings revealed that GXNT could reduce lipid deposition, alleviate AS lesions, and restrain the expressions of NF-κB, TNF-α, and MMP-9. Furthermore, the composition of the gut microbiota was altered. Specifically, GXNT could upregulate the relative abundance of Prevotellaceae and Prevotella and downregulate the abundance of Proteobacteria, Enterobacteriaceae, and Escherichia. As for microbial metabolites, GXNT could increase fecal propionic acid, butyric acid, and LCA-3S and decrease fecal TMA-related metabolites, CDCA, and serum TMAO. In sum, the results showed that GXNT had a satisfactory anti-CA effect, and the mechanism was closely associated with modulating gut microbiota and related metabolites.

Vasodilatory therapy plays an important role in the treatment of cardiovascular diseases, especially hypertension and coronary heart disease. Previous research found that Guanxinning tablet (GXNT), a traditional Chinese compound preparation composed of Salvia miltiorrhiza (Danshen) and Ligusticum chuanxiong (Chuanxiong), increase blood flow in the arteries, but whether vasodilation plays a role in this effect remains unclear. Here, we found that GXNT significantly alleviated the vasoconstriction of isolated rabbit thoracic aorta induced by phenylephrine (PE), norepinephrine (NE), and KCl in a dose-dependent manner with or without endothelial cells (ECs). Changes in calcium ion levels in vascular smooth muscle cells (VSMCs) showed that both intracellular calcium release and extracellular calcium influx through receptor-dependent calcium channel (ROC) declined with GXNT treatment. Experiments to examine potassium channels suggested that endothelium-denuded vessels were also regulated by calcium-activated potassium channels (Kca) and ATP-related potassium channels (KATP) but not voltage-gated potassium channels (kv) and inward rectifying potassium channels (KIR). For endothelium-intact vessels, the nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) contents in vascular tissue obviously increased after GXNT treatment, and pretreatment with the NO synthase inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) or guanylyl cyclase inhibitor methylthionine chloride (MB) significantly inhibited vasodilation. An assessment of NO-related pathway protein expression revealed that GXNT enhanced the expression of phosphorylated endothelial NO synthase (eNOS) in a dose-dependent manner but had no effect on total eNOS, p-Akt, Akt, or PI3K levels in human umbilical vein ECs (HUVECs). In addition to PI3K/AKT signaling, Ca2+/calmodulin (CaM)-Ca2+/CaM-dependent protein kinase II (CaMKII) signaling is a major signal transduction pathway involved in eNOS activation in ECs. Further results showed that free calcium ion levels were decreased in HUVECs with GXNT treatment, accompanied by an increase in p-CaMKII expression, implying an increase in the Ca2+/CaM-Ca2+/CaMKII cascade. Taken together, these findings suggest that the GXNT may have exerted their vasodilative effect by activating the endothelial CaMKII/eNOS signaling pathway in endothelium-intact rings and calcium-related ion channels in endothelium-denuded vessels.

Objective: An increasing number of studies have demonstrated that circular RNAs (circRNAs) are involved in tumor progression. However, the role of hsa_circ_0000073 in osteosarcoma (OS) is still not fully elucidated.Methods: Quantitative reverse transcription-polymerase chain reaction or Western blot was used to detect the gene expression. GeneChip analysis, bioinformatics, luciferase reporter, and RNA immunoprecipitation assays were adopted to predict and verify the relationships between genes. Counting Kit-8 Assay, clone formation assay, wound-healing assay, transwell assays, cell cycle assays, and in vivo tumorigenesis were used to evaluate cell function.Results: hsa_circ_0000073 was highly expressed in OS cell lines and could promote OS progression, including proliferation, migration, invasion, and cell cycle in vitro as well as tumorigenesis in vivo. Mechanically, hsa_circ_0000073 could readily downregulate the expression of CCNE2 and MDM2 through miR-1252-5p. Rescue experiments validated miR-1252-5p mimics, or CCNE2/MDM2 short hairpin RNA could reverse the hsa_circ_0000073 overexpressing-induced impairment of malignant tumor behavior.Conclusion: hsa_circ_0000073 functions as a tumor promoter in OS to increase malignant tumor behavior through sponging miR-1252-5p and regulating CCNE2 and MDM2 expression, which could be a novel target for OS therapy.

Heading date (HD) is one of the agronomic traits that influence maturity, regional adaptability, and grain yield. The present study was a follow-up of a previous quantitative trait loci (QTL) mapping study conducted on three populations, which uncovered a total of 62 QTLs associated with 10 agronomic traits. Two of the QTLs for HD on chromosome 7 (qHD7a and qHD7b) had a common flanking marker (RM3670) that may be due to tight linkage, and/or weakness of the statistical method. The objectives of the present study were to map QTLs associated with HD in a set of 76 chromosome segment substitution lines (CSSLs), fine map and validate one of the QTLs (qHD7b) using 2997 BC5F2:3 plants, and identify candidate genes using sequencing and expression analysis. Using the CSSLs genotyped with 120 markers and evaluated under two short-day and two long-day growing conditions, we uncovered a total of fourteen QTLs (qHD2a, qHD4a, qHD4b, qHD5a, qHD6a, qHD6b, qHD7b, qHD7c, qHD8a, qHD10a, qHD10b, qHD11a, qHD12a, and qHD12b). However, only qHD6a and qHD7b were consistently detected in all four environments. The phenotypic variance explained by qHD6a and qHD7b varied from 10.1% to 36.1% (mean 23.1%) and from 8.1% to 32.8% (mean 20.5%), respectively. One of the CSSL lines (CSSL52), which harbored a segment from the early heading XieqingzaoB (XQZB) parent at the qHD7b locus, was then used to develop a BC5F2:3 population for fine mapping and validation. Using a backcross population evaluated for four seasons under different day lengths and temperatures, the qHD7b interval was delimited to a 912.7-kb region, which is located between RM5436 and RM5499. Sequencing and expression analysis revealed a total of 29 candidate genes, of which Ghd7 (Os07g0261200) is a well-known gene that affects heading date, plant height, and grain yield in rice. The ghd7 mutants generated through CRISPR/Cas9 gene editing exhibited early heading. Taken together, the results from both the previous and present study revealed a consistent QTL for heading date on chromosome 7, which coincided not only with the physical position of a known gene, but also with two major effect QTLs that controlled the stigma exertion rate and the number of spikelets in rice. The results provide contributions to the broader adaptability of marker-assisted breeding to develop high-yield rice varieties.

Plant height (PH) is one of the most important agronomic traits determining plant architecture in rice. To investigate the genetic basis of plant height in the high-yielding hybrid rice variety Nei2You No.6, recombinant inbred sister lines (RISLs) were used to map quantitative trait loci (QTL) over four years. A total of 19 minor/medium-effect QTLs were mapped on eleven chromosomes except chromosome 10, totally explaining 44.61–51.15% phenotypic variance in four environments. Among these, qPH-1a, qPH-1b, qPH-2b, qPH-3b, qPH-6, and qPH-7b were repeatedly detected over four years. Among these, the qPH-6 was mapped to an interval of 22.11–29.41 Mb on chromosome 6L, which showed the highest phenotypic variation explained (PVE) of 10.22–14.05% and additive effect of 3.45–4.63. Subsequently, evaluation of near isogenic lines (NILs) showed that the qPH-6 allele from the restorer line (R8006) could positively regulate plant height, resulting in an 18.50% increase in grain yield. These results offered a basis for further mapping of qPH-6 and molecular breeding in improving plant architecture in rice.

Abstract Background As a major lignocellulosic biomass, which represented more than half of the world’s agricultural phytomass, crop residues have been considered as feedstock for biofuel production. However, large-scale application of this conventional biofuel process has been facing obstacles from cost efficiency, pretreatment procedure, and secondary pollution. To meet the growing demands for food, feed, and energy as the global population continues to grow, certain kinds of insects, many of which are voracious feeders of organic wastes that may help address environmental, economic, and health issues, have been highlighted as a source of protein and fat. Results The biorefinery studied includes initial corn stover degradation by yellow mealworm (Tenebrio molitor L.), followed by a second stage that employs black soldier fly (Hermetia illucens L.), to utilize the residues produced during the first stage. These two insect-based biorefinery yielded 8.50 g of insect biomass with a waste dry mass reduction rate of 51.32%, which resulted in 1.95 g crude grease from larval biomass that produced 1.76 g biodiesel, 6.55 g protein, and 111.59 g biofertilizer. The conversion rate of free fatty acids of crude grease into biodiesel reached 90%. The components of cellulose, hemicellulose, and lignin contained in corn stover hydrolyzed harmoniously, resulting in declines of 45.69, 51.85, and 58.35%, respectively. Moreover, fluctuations in lipid, protein, and reducing sugar were also analyzed. Conclusion The investigation findings demonstrated that successive co-conversion of corn stover by insects possessing different feeding habits could be an attractive option for efficient utilization of lignocellulosic resources, and represents a potentially valuable solution to crop residues management, rise of global liquid energy, and animal feed demand.

Salvianolic acid A (SAA), an important bioactive polyphenolic acid found in Salvia miltiorrhiza Bunge, may be used for treating metabolic disorders due to its anti-inflammatory activity. Since chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM) complicated with atherosclerosis (AS), SAA may have beneficial effects on AS. Here, we evaluated the effects of SAA on metabolic disorders in male Zucker diabetic fatty (ZDF) rats induced by a high-fat diet and Vitamin D3 injections. Compared with the model group, the SAA high dosage (1 mg/kg) group exhibited decreased hemoglobin A1C levels but unchanged blood glucose levels. The disrupted lipid profiles were ameliorated by SAA, with significantly decreased levels of blood cholesterol, LDL-C and triglyceride. The protective effects of SAA against early AS were further confirmed by histopathological examination of aortic tissues. In addition, we observed that SAA decreased serum hs-CRP levels and suppressed the activation of NLRP3 inflammasome and NF-κB signaling in aortic tissues of ZDF rats. Collectively, our results demonstrate the potential of SAA to alleviate AS and T2DM in ZDF rats as a result of its anti-inflammatory effects.

Black soldier fly (BSF) larvae, Hermetia illucens L., develops on organic wastes, reducing ecological pollution and converting waste biomass into protein and fat rich insect biomass. BSF can replace increasingly expensive protein sources used in poultry, aquaculture and livestock compound diet formulation, such as fish meal and soybean meal, which holds the potential to alleviate future food and feed insecurity. The fate of nutritional spectra in BSF during its life cycle phases is still poorly understood. This study assessed metabolic changes in nutrition composition of BSF from egg to adult. A rapid increase of crude fat content was observed since the development of 4-14 days of larvae with its maximum level reaching 28.4% in dry mass, whereas the crude protein displayed a continuous decreasing trend in the same development phases with minimum level of 38% at larval phase (12 days) and peak level of 46.2% at early pupa stage. A sharp drop in crude fat was noticed from early prepupae to late pupae (24.2%, 8.2% respectively). However crude protein shows its maximum value being 57.6% at postmortem adult stage with 21.6% fat level. In addition, fatty acids, amino acids, minerals and vitamins composition in different development stages of BSF were presented and compared. Findings from this study could provide podium to food and feed industry for framing a strategy for specific molecular nutritional component intake into the diets of humans, aquaculture and animals. It is also indicated that BSF is a possible insect which can be applied to combating the food scarcity of countries where micronutrient deficiency is prevalent. Moreover it contributes to advance exploring for developmental and metabolic biology of this edible insect.

Estrogen deficiency after menopause is associated with autonomic nervous changes, leading to memory impairment and increased susceptibility to Alzheimer’s disease (AD). Royal jelly (RJ) from honeybees (Apis mellifera) has estrogenic activity. Here, we investigated whether RJ can improve behavior, cholinergic and autonomic nervous function in ovariectomized (OVX) cholesterol-fed rabbits. OVX rabbits on high-cholesterol diet were administered with RJ for 12 weeks. The results showed that RJ could significantly improve the behavioral deficits of OVX cholesterol-fed rabbits and image structure of the brain. RJ reduced body weight, blood lipid, as well as the levels of amyloid-beta (Aβ), acetylcholinesterase (AchE), and malonaldehyde (MDA) in the brain. Moreover, RJ also increased the activities of choline acetyltransferase (ChAT) and superoxide dismutase (SOD) in the brain, and enhanced heart rate variability (HRV) and Baroreflex sensitivity (BRS) in OVX cholesterol-fed rabbits. Furthermore, RJ was also shown to reduce the content of Evans blue and the expression levels of Aβ, beta-site APP cleaving enzyme 1(BACE1), and receptor for advanced glycation end products (RAGE), and increase the expression level of LDL(low density lipoprotein) receptor-related protein 1 (LRP-1) in the brain. Our findings suggested that RJ has beneficial effects in neurological disorders of postmenopausal women, which were associated with reducing cholesterol and Aβ deposition, enhancing the estrogen levels and the activities of cholinergic and antioxidant systems, and ameliorating the blood–brain barrier (BBB) permeability and restoring autonomic nervous system.

Veronicastrum axillare is a traditional medical plant in China which is widely used in folk medicine due to its versatile biological activities, especially for its anti-inflammatory effects. However, the detailed mechanism underlying this action is not clear. Here, we studied the protective effects of V. axillare against acute lung injury (ALI), and we further explored the pharmacological mechanisms of this action. We found that pretreatment with V. axillare suppressed the release of proinflammatory cytokines in the serum of ALI mice. Histological analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung injury, improved lung morphology, and reduced the activation of nuclear factor-κB (NF-κB) in the lungs. Furthermore, the anti-inflammatory actions of V. axillare were investigated in vitro. We observed that V. axillare suppressed the mRNA expression of interleukin-1β (IL-1β), IL-6, monocyte chemotactic protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V. axillare in vitro reduced the phosphorylation of p65 and IκB-α which is activated by LPS. In conclusion, our data firstly demonstrated that the anti-inflammatory effects of V. axillare against ALI were achieved through downregulation of the NF-κB signaling pathway, thereby reducing the production of inflammatory mediators.

Salvianolic acid A (SAA) is an active phenolic acid derived from Salvia miltiorrhiza Bunge (Danshen). To explore whether SAA has a therapeutic effect against inflammatory bowel disease (IBD), an acute colitis model was induced in rats by administering 3% dextran sodium sulphate (DSS) for one week. SAA in doses of 4 and 8 mg/kg/day was given by tail vein injection during DSS administration. Both dosages of SAA ameliorated the colitis symptoms, with decreases observed in the disease activity index. A high dosage of SAA (8 mg/kg/day) promoted a longer colon length and an improved colonic tissue structure, compared with the DSS-treated rats not receiving SAA. SAA dose-dependently decreased colonic gene expression of pro-inflammatory cytokines (IL-1β, MCP-1 and IL-6). Moreover, a high dosage of SAA protected against DSS-induced damage to tight junctions (TJ) in the rats’ colons, by increasing TJ-related gene expression (ZO-1 and occuldin). Finally, using 16S rRNA phylogenetic sequencing, we found that SAA modulated gut microbiota imbalance during colitis by increasing the gut microbial diversity as well as selectively promoting some probiotic populations, including Akkermansia spp. Our study suggests that SAA is a promising candidate for the treatment of IBD.