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It is crucial to explore the impact of dietary interventions on depression and develop functional antidepressant foods, due to the significant side effects and poor treatment compliance of antidepressant drugs. Osmanthus fragrans flowers are edible and medicinal materials owing to their delightful floral aroma and significant health benefits. Here, we evaluated the antidepressant effects of the ethanolic extract of O. fragrans var. thunbergii flowers (OFE) and investigated the mechanisms of action on the serotonin system and neuroinflammation, and analyzed the main chemical components of OFE. A single administration of OFE significantly reduced the immobility duration in the forced swimming and tail suspension tests in mice without affecting locomotor activity. OFE exhibited selective enhancing effects on 5‐HTergic function in vivo, as demonstrated by its potentiating effects on 5‐hydroxytryptophan (5‐HTP)‐induced head‐twitch behavior and alleviation effects on reserpine‐induced ptosis deficits. In addition, OFE increased 5‐hydroxytryptamine (5‐HT) concentration and upregulated 5‐HT1A expression in reserpine‐treated mice, further validating its effects on 5‐HT transmission. Interestingly, OFE significantly alleviated microglia activation and the production of inflammatory mediators, both in reserpine‐treated mice in vivo and lipopolysaccharide (LPS)‐stimulated BV‐2 cells in vitro. Additionally, 62 components in OFE were identified using ultra‐performance liquid chromatography quadrupole time‐of‐flight high‐resolution mass spectrometry, and glycoside derivatives were shown to be the major constituents of OFE. The present study showed that OFE can alleviate depressive‐like behaviors by modulating the serotonin system and reducing neuroinflammation. These results suggest that OFE can be valuable dietary supplements with therapeutic effects on depression. [ABSTRACT FROM AUTHOR]

The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues. [ABSTRACT FROM AUTHOR]

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-β-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy. [ABSTRACT FROM AUTHOR]

Summary: Cultivated peanut (Arachis hypogaea L.) is an important oil and cash crop. Pod size is one of the major traits determining yield and commodity characteristic of peanut. Fine mapping of quantitative trait locus (QTL) and identification of candidate genes associated with pod size are essential for genetic improvement and molecular breeding of peanut varieties. In this study, a major QTL related to pod size, qAHPS07, was fine mapped to a 36.46 kb interval on chromosome A07 using F2, recombinant inbred line (RIL) and secondary F2 populations. qAHPS07 explained 38.6%, 23.35%, 37.48%, 25.94% of the phenotypic variation for single pod weight (SPW), pod length (PL), pod width (PW) and pod shell thickness (PST), respectively. Whole genome resequencing and gene expression analysis revealed that a RuvB‐like 2 protein coding gene AhRUVBL2 was the most likely candidate for qAHPS07. Overexpression of AhRUVBL2 in Arabidopsis led to larger seeds and plants than the wild type. AhRUVBL2‐silenced peanut seedlings represented small leaves and shorter main stems. Three haplotypes were identified according to three SNPs in the promoter of AhRUVBL2 among 119 peanut accessions. Among them, SPW, PW and PST of accessions carrying Hap_ATT represent 17.6%, 11.2% and 26.3% higher than those carrying Hap_GAC，respectively. In addition, a functional marker of AhRUVBL2 was developed. Taken together, our study identified a key functional gene of peanut pod size, which provides new insights into peanut pod size regulation mechanism and offers practicable markers for the genetic improvement of pod size‐related traits in peanut breeding. [ABSTRACT FROM AUTHOR]

Background: Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta‐analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment. Methods: Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle. Results: Meta‐analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin‐antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta‐analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1‐INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose‐ and time‐dependent manner in the MCAO models. Conclusions: Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1‐INH and FUT175 could be potential medications for IS. [ABSTRACT FROM AUTHOR]

Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93–10.18, P = 9.51 × 10–08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment. [ABSTRACT FROM AUTHOR]

The role of the mechanical environment in defining tissue function, development and growth has been shown to be fundamental. Assessment of the changes in stiffness of tissue matrices at multiple scales has relied mostly on invasive and often specialist equipment such as AFM or mechanical testing devices poorly suited to the cell culture workflow.In this paper, we have developed a unbiased passive optical coherence elastography method, exploiting ambient vibrations in the sample that enables real-time noninvasive quantitative profiling of cells and tissues. We demonstrate a robust method that decouples optical scattering and mechanical properties by actively compensating for scattering associated noise bias and reducing variance. The efficiency for the method to retrieve ground truth is validated in silico and in vitro, and exemplified for key applications such as time course mechanical profiling of bone and cartilage spheroids, tissue engineering cancer models, tissue repair models and single cell. Our method is readily implementable with any commercial optical coherence tomography system without any hardware modifications, and thus offers a breakthrough in on-line tissue mechanical assessment of spatial mechanical properties for organoids, soft tissues and tissue engineering. A method is described for assessing spatial mechanical properties for organoids, soft tissues and tissue engineering. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: The genus Polygonatum Tourn, ex Mill. contains numerous chemical components, such as steroidal saponins, polysaccharides, flavonoids, alkaloids, and others, it possesses diverse pharmacological activities, such as anti-aging, anti-tumor, immunological regulation, as well as blood glucose management and fat reducing properties. Aim of the review: This study reviews the current state of research on the systematic categorization, chemical composition, pharmacological effects, and processing changes of the plants belonging to the genus Polygonatum, to provide a theoretical foundation for their scientific development and rational application. Materials and methods: The information was obtained by searching the scientific literature published between 1977 and 2022 on online databases (including PubMed, CNKI, SciFinder, and Web of Science) and other sources (such as the Chinese Pharmacopoeia 2020 edition, and Chinese herbal books). Results: The genus Polygonatum contains 79 species, and 233 bioactive chemical compounds were identified in them. The abundance of pharmacological activities, such as antioxidant activities, anti-fatigue activities, anti-inflammatory activities, etc., were revealed for the representatives of this genus. In addition, there are numerous processing methods, and many chemical constituents and pharmacological activities change after the unappropriated processing. Conclusions: This review summarizes the taxonomy classification, chemical composition, pharmacological effects, and processing of the plants belonging to the genus Polygonatum, providing references and research tendencies for plant-based drug development and further clinical applications. [ABSTRACT FROM AUTHOR]

Background. Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia–reperfusion injury. Methods. We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results. Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion. These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study. [ABSTRACT FROM AUTHOR]

Background: Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization.Methods: We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing.Results: ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1β, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1β, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment.Conclusions: rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke. [ABSTRACT FROM AUTHOR]

The Ti 3 C 2 T x with excellent conductivity is used to design a novel cobalt-based ZIF-67/Ti 3 C 2 T x composite, sulfide derivative (Co 3 S 4 /Ti 3 C 2 T x) of which is then applied as an active supercapacitor material. The excellent electrochemical performance of the novel composite, as well as the stability of its three-dimensional (3D) structure, make it a very promising material for energy storage applications. [Display omitted] The Ti 3 C 2 T x with excellent conductivity is used in a novel cobalt-based ZIF-67/Ti 3 C 2 T x composites, sulfide derivative (Co 3 S 4 /Ti 3 C 2 T x) of which is then applied as an active supercapacitor material. The specific capacitance of ZIF-67/Ti 3 C 2 T x is significantly higher than that of unmodified ZIF-67. The sulfide-containing derivatives of these compounds demonstrated pseudocapacitance. The specific capacitance of an electrode containing Co 3 S 4 /Ti 3 C 2 T x as an active material is very high and equal to 602F/g at 1 A/g, which is 2.6 times higher than of a ZIF-67/Ti 3 C 2 T x -containing electrode. The supercapacitor based on Co 3 S 4 /Ti 3 C 2 T x maintained 81.6% of its original capacitance even at 10 A/g current density. Thus, the introduction of Ti 3 C 2 T x into the ZIF-67 improves not only the electrical conductivity of the hybrid material but also its structural stability, which allows to act as support. An asymmetric Co 3 S 4 /Ti 3 C 2 T x //AC supercapacitor (ASC) containing activated carbon (AC) as an anode showed a high energy density equal to 44.9 Wh/kg at 800.3 W/kg power density. This ASC also demonstrated high rate-performance (equal to 79.2%) and excellent cycling stability (with 88.3% capacitance retention and 99.23% Coulombic efficiency after 5000 cycles). The excellent electrochemical performance of our novel composite and conductivity, as well as the stability of its three-dimensional (3D) structure, make it a very promising material for energy storage applications. [ABSTRACT FROM AUTHOR]

Auxin response factors (ARFs) play important roles in plant growth and development; however, research in peanut (Arachis hypogaea L.) is still lacking. Here, 63, 30, and 30 AhARF genes were identified from an allotetraploid peanut cultivar and two diploid ancestors (A. duranensis and A. ipaensis). Phylogenetic tree and gene structure analysis showed that most AhARFs were highly similar to those in the ancestors. By scanning the whole-genome for ARF-recognized cis-elements, we obtained a potential target gene pool of AhARFs, and the further cluster analysis and comparative analysis showed that numerous members were closely related to root development. Furthermore, we comprehensively analyzed the relationship between the root morphology and the expression levels of AhARFs in 11 peanut varieties. The results showed that the expression levels of AhARF14/26/45 were positively correlated with root length, root surface area, and root tip number, suggesting an important regulatory role of these genes in root architecture and potential application values in peanut breeding. [ABSTRACT FROM AUTHOR]

Although skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke-related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop effective rehabilitation strategy. Here, we evaluated the effects of high-intensity interval (HIIT) versus moderate-intensity aerobic training (MOD) on physical function, muscle mass, and stroke-related gene expression profile of skeletal muscle. After the model of middle cerebral artery occlusion (MCAO) was successfully made, the blood lactate threshold corresponding speed ( S LT ) and maximum speed ( S max ) were measured. Different intensity training protocols (MOD < S LT ; S LT < HIIT < S max ) were carried out for 3 weeks beginning at 7 days after MCAO in the MOD and HIIT groups, respectively. We found that both HIIT and MOD prevented stroke-related gastrocnemius muscle mass loss in MCAO mice. HIIT was more beneficial than MOD for improvements in muscle strength, motor coordination, walking competency, and cardiorespiratory fitness. Furthermore, HIIT was superior to MOD in terms of reducing lipid accumulation, levels of IL-1β and IL-6 in paretic gastrocnemius, and improving peripheral blood CD4+/CD8+ T cell ratio, level of IL-10. Additionally, RNA-seq analysis revealed that the differentially expressed genes among HIIT, MOD, and MCAO groups were highly associated with signaling pathways involved in inflammatory response, more specifically the I-kappaB kinase/NF-kappaB signaling. Following the outcome, we further investigated the infiltrating immune cells abundant in paretic muscles. The results showed that HIIT modulated macrophage activation by downregulating CD86+ (M1 type) macrophages and upregulating CD163+ (M2 type) macrophages via inhibiting the TLR4/MyD88/NFκB signaling pathway and exerting an anti-inflammatory effect in paretic skeletal muscle. It is expected that these data will provide novel insights into the mechanisms and potential targets underlying muscle wasting in stroke. [ABSTRACT FROM AUTHOR]

[Display omitted] • OH and CH 3 C(O)OO were identified as the main reactive species in UV/PAA process. • CH 3 C(O)OO exhibited lower reaction rates but higher concentration compared to OH. • RAF was proposed as the main initial reaction mechanism in UV/PAA process. • CH 3 C(O)OO possessed higher selectivity than OH towards TrOCs. Peracetic acid (PAA) is a promising peroxyacid to combine with ultraviolet (UV) to eliminate trace amounts of organic contaminants (TrOCs), with growing importance in water treatment. In spite of a large number of research on UV/PAA process, the underlying mechanism still require further investigation, due to the difficulties in analyzing the carbon-centered radicals. Here we demonstrated the crucial roles of the carbon-centered radicals (namely CH 3 C(O)OO), via electron paramagnetic resonance (EPR) and kinetic models, with concentration of 4 orders magnitude higher than that of OH. Then, the theoretical calculation using density functional theory (DFT) showed that CH 3 C(O)OO and OH tended to attack phenol mostly through the route of radical adduct formation. The generated CH 3 C(O)OO and OH adducts may undergo further reactions to produce catechol and hydroquinone. Further, the environmental applicability of UV/PAA process for TrOC abatement was evaluated, including the effects of pH, PAA dosage, water constituents, as well as the variation of acute toxicity. Different from the OH-dominated process, kinetic analysis revealed that CH 3 C(O)OO was almost immune to the presence of water constituents, leading to the outperformance of UV/PAA process in actual water samples. Our present study could inform the application of UV/PAA process in water and wastewater treatment. [ABSTRACT FROM AUTHOR]

An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats. [ABSTRACT FROM AUTHOR]

Knowledge of the optimal protocol and safety of particularly high-intensity exercise applied to individuals with stroke is lacking. This systematic review and meta-analysis aimed to investigate the effect of high-intensity exercise on cardiorespiratory fitness in stroke survivors. We performed a systematic electronic search for articles in MedLine via PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, CINAHL, and SPORTSDiscus up to April 1, 2019. Peak oxygen consumption (VO 2 peak), 6-min walk test (6MWT), fastest 10-m walk test (10MWT), and adverse events were assessed. The standardized mean difference (SMD), weighted mean difference (WMD), and odds ratios (ORs) were used to compute the effect size, and subgroup analysis was conducted to test the consistency of results as well as sensitivity analysis to assess the robustness of the results. The quality of evidence was assessed with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We included 17 studies (PEDro score ≥ 4) in the meta-analysis. Post-intervention, high-intensity exercise had a significant effect on peak oxygen uptake (VO 2 peak; SMD = 0.56, P < 0.01, I2 = 8%; WMD = 2.53 mL/kg/min; high quality of evidence) and 6MWT (SMD = 0.26, P < 0.01, I2 = 40%; WMD = 17.08 m; moderate quality of evidence) but not fastest 10MWT (SMD = 0.33, P = 0.27, I2 = 77%; WMD = 0.05 m/s; low quality of evidence). Subgroup analysis showed better effects of higher-intensity treadmill training (≥ 70% heart rate reserve/VO 2 peak) for a longer duration (≥ 12 weeks) on VO 2 peak and 6MWT in sub-acute or chronic stroke survivors. The high-intensity exercise and control groups did not differ in adverse events including falls [odds ratio (OR) 1.40, P = 0.35, I2 = 11%; low quality of evidence], pain (OR 3.34, P = 0.09, I2 = 0%; moderate quality of evidence), or skin injuries (OR 1.08, P = 0.90, I2 = 0%; low quality of evidence). Our meta-analysis suggests that high-intensity exercise is beneficial for cardiorespiratory fitness in stroke survivors and might be safe as a novel intervention in cardiopulmonary rehabilitation after stroke. [ABSTRACT FROM AUTHOR]

Introduction: Many studies have shown that multifetal reduction of high-order multiple pregnancies results in improved pregnancy outcomes. However, whether conducting elective fetal reduction from dichorionic twins after in vitro fertilization (IVF) is worthwhile remains controversial. This study aimed to determine whether elective fetal reduction of dichorionic twins after IVF and embryo transfer (IVF-ET) is associated with increased take-home baby rate.Material and Methods: This was a retrospective cohort study of 3600 dichorionic twin pregnancies after IVF-ET. The reduced group included 71 women with transvaginal elective fetal reduction between 7 and 8 weeks of gestation. The control group (n = 3529) comprised women who were managed expectantly. Propensity score matching was conducted before pregnancy outcomes were compared.Results: The take-home baby rate was significantly lower in the reduced group (83.1% vs 92.8%, P = 0.004). The total miscarriage rate was significantly higher in the reduced group (12.7% vs 6.2%, P = 0.04). Although preterm delivery rate was lower in the reduced group (P < 0.001), over 90% were over 32 weeks, whereas the proportions were equal in the reduced group.Conclusions: In dichorionic twin pregnancies after IVF-ET, elective fetal reduction to singleton significantly decreased the chance of taking home live babies. [ABSTRACT FROM AUTHOR]

Abstract In this work, a highly concentrated Mg-18 wt%Gd binary alloy was prepared and its tensile creep behaviors were studied. Both as-solution (AS) and as-aged (AA) samples were subjected to creep tests at 523 K under various stresses. The results showed that precipitate variants and sizes became similar in AS and AA samples during their secondary creep stages. Strain aging and artificial aging play equivalent roles in the strengthening effects on AS and AA samples. Dislocation climb composed by edge < a > dislocations was the dominant creep mechanism of AS sample, and dislocations bypassing precipitates strengthened AS sample limitedly. By contrast, cross-slip composed by basal < a > and prismatic < a > dislocations was the dominant creep mechanism of AA sample, and dislocations cutting precipitates strengthened AA sample obviously. Furthermore, compared to AS sample, a high density of precipitate-free zones (PFZs) were developed in AA sample during creep testing. These high-density PFZs then relieved local stress concentration and catalyzed a homogeneous stress distribution, which postponed the occurrence of creep rupture rather than accelerated it. Accordingly, AA sample had an increased creep resistance than that of AS sample at 523 K. This unexpected discovery that PFZs could contribute to the increase in creep resistance is believed to extend the application of the Mg-Gd alloys with vast potentials. Graphical abstract Image 1 Highlights • As-solution (AS) and as-aged (AA) Mg-18Gd alloys are creep tested at 523 K. • Dislocation climb is the dominant creep mechanism of AS sample. • Cross-slip is the dominant creep mechanism of AA sample. • A higher density of precipitate-free zone (PFZ) is observed in AA sample. • High-density PFZs lead to an amazing enhancement of creep resistance of AA sample. [ABSTRACT FROM AUTHOR]

Purpose Determine the frequency and prognostic value of circulating Epstein-Barr virus (EBV) DNA copy number in angioimmunoblastic T-cell lymphoma (AITL) patients who were treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH) regimens. Materials and Methods Sixty newly-diagnosed AITL patients were retrospectively enrolled in the present study. All patients were treated with DA-EPOCH regimen. Results Twenty-two subjects (36.7%) had a EBV DNA-positive test at diagnosis. EBV DNA-positive patients were associated with lower lymphocyte-monocyte ratio (p=0.024). Median followup was 40 months (range, 14 to 100 months). The overall response rate for all the 60 AITL patents were 71.7% (95% confidence interval [CI], 58.6 to 82.5) with 3-year progressivefree survival (PFS) rate of 30.9%±6.1% and overall survival (OS) rate of 60.1%±6.6%. Not only did PFS estimation differ between the EBV DNA-positive and EBV DNA-negative group (hazard ratio [HR], 2.24,95% CI, 1.15 to 4.35,p=0.006), but also worse OS was observed in the pretreatment EBV DNA-positive group than in the EBV DNA-negative group (HR, 2.74,95% CI, 1.22 to 6.19,p=0.006). EBV DNA test positivity was independent prognostic marker for both PFS (HR, 2.17,95% CI, 1.17 to 4.00,p=0.014) and OS (HR, 3.24,95% CI, 1.48 to 7.11,p=0.004) after adjusting International Prognostic Index and prognostic index for AITL score. Reduction in EBV copies was significantly associated with therapy-response. Conclusion Circulating EBV DNA level was an important prognostic and monitoring marker for AITL patients who treated with DA-EPOCH regimens which cannot improve outcomes for AITL patients. [ABSTRACT FROM AUTHOR]

A hot-extruded AZ80 Mg alloy rod was subjected to pre-treatments and post-hot compression in this work. Microstructure evolutions and resultant mechanical properties were investigated using samples with different states. The sample processed by solid solution and pre-aging (SSA) contained large-scale precipitates at the triple points of grain boundaries, while the sample processed by solid solution, pre-deformation and pre-aging (SSPDA) contained fine precipitates and different types of dislocations in the {10–12} twin interiors. Meanwhile, substructures were formed through dislocations surrounding the fine precipitates in SSPDA sample. During hot compression at 593 K, continuous dynamic recrystallization (DRX) was promoted by substructures in SSPDA sample, resulting in a full development of fine grains and a weakened texture. Inversely, discontinuous DRX happened in SSA sample, resulting in a low volume fraction of DRX grains and a relatively strong texture. The tensile testing showed that SSPDA sample had much higher strength and ductility than those of SSA sample. The enhanced mechanical properties were attributed to the completely developed DRX with grain refinement and texture weakening. [ABSTRACT FROM AUTHOR]

Agarwood, a highly valuable resin/wood combination with diverse pharmacological activities but scarce supply, has a long history of being used as a medicine in several medical systems. Grafted Kynam agarwood (GKA) has been cultivated successfully recently and has the qualities meeting the definition of premium Kynam agarwood. However, there are few comprehensive comparisons between GKA and normal agarwood in terms of traits, global composition, and activity, and some key issues for GKA to be adopted into the traditional Chinese medical (TCM) system have not been elaborated. The two types of agarwood samples were evaluated in terms of trait characteristics, physicochemical indicators, key component groups, and global compositional profile. Furthermore, a molecular docking was performed to investigate the active ingredients. In vitro activity assays were performed to evaluate the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) by GKA and normal agarwood. The results revealed that, overall, the traits, microscopic characteristics, chemical composition types, and bioactivity between GKA and normal agarwood were similar. The main differences were the content of resin (ethanolic extract content), the content of key component groups, and the composition of the different parent structural groups of 2-(2-phenethyl) chromones (PECs). The contents of total PEC and ethanol extract content of GKA were significantly higher than those of normal agarwood. The MS-based high-throughput analysis revealed that GKA has higher concentrations of sesquiterpenes and flindersia-type 2-(2-phenylethyl) chromones (FTPECs) (m/z 250-312) than normal agarwood. Molecular docking revealed that parent structural groups of FTPECs activated multiple signaling pathways, including the AMPK pathway, suggesting that FTPECs are major active components in GKA. The aim of this paper is to describe the intrinsic reasons for GKA as a high-quality agarwood and a potential source for novel drug development. We combined high-throughput mass spectrometry and multivariate statistical analysis to infer the different components of the two types of agarwood. Then we combined virtual screening and in vitro activity to construct a component/pharmacodynamic relationship to explore the causes of the activity differences between agarwood with different levels of quality and to identify potentially valuable lead compounds. This strategy can also be used for the comprehensive study of other TCMs with different qualities. [ABSTRACT FROM AUTHOR]

Highlights: [•] The effect of fiber volume fraction on crack propagation rate of UHTCC is investigated. [•] The crack propagation thresholds of UHTCC with three different fiber fractions are calculated. [•] The effect of fatigue loads on crack propagation rate of UHTCC is investigated. [Copyright &y& Elsevier]

CCCTC binding factor (CTCF) controls DNA imprinting, insulates important gene expression, and mediates growth factorand stress-induced cell fate. However, regulatory mechanisms involved in intracellular CTCF activity are largely unknown. In this study, we show that epidermal growth factor (EGF)-induced increase and UV stress-induced decrease in CTCF activities mediate human corneal epithelial cell proliferation and apoptosis, respectively. CTCF is regulated by activation of different NF-κB subtypes via stimulation by EGF and UV stress. EGF-induced formation of a p651p50 heterodimer activated CTCF transcription to promote cellular proliferation. This was accomplished by the heterodimer binding to a KB site in the promoter region of CTCF gene. In contrast, UV stress induced formation of a p50/p50 homodimer, which suppressed CTCF expression leading to apoptosis. Thus, CTCF by itself plays a central role in mediating the dichotomous effects of growth factor and stress-stimulated NF-κB activation on cell survival and death. These results suggest that CTCF is a downstream component of the NF-κB pathway involved in the core transcriptional network of cell fate. [ABSTRACT FROM AUTHOR]

Growth factors play important roles in regulating corneal epithelial cell proliferation/differentiation during wound healing. It is suggested that PAX6 involves corneal epithelium lineage-specific differentiation (Liu, J. J., Kao, W. W., and Wilson, S. E. (1999) Exp. Eye Res. 68, 295–301); however, the regulatory mechanism and function of Pax6 in growth factor-induced corneal epithelial responses is still unknown. In the present study, we found that the mitogenic effect of epidermal growth factor (EGF) in corneal epithelial cells required suppression of PAX6 activity through cellular mechanisms involving Erk-signaling pathway-mediated increase in CTCF expression. EGF-induced CCCTC binding factor (CTCF) activation subsequently inhibited Pax6 expression by interacting with a CTCF-specific region upstream of the pax6 P0 promoter. Suppression of EGF-induced Erk activation by specific inhibitor or by the dominant expression of a silent Erk mutant effectively abolished the effects of EGF stimulation on regulations of CTCF and pax6. Apparently, down-regulation of Pax6 expression induced by EGF is required for corneal epithelial proliferation, because overexpression of pax6 in these cells attenuated EGF-induced proliferation. In contrast, knockdown of mRNA expression with pax6- or CTCF-specific small interfering RNA in corneal epithelial cells significantly promoted or attenuated EGF-induced proliferation, respectively. Thus, our results revealed a new regulatory mechanism that involves cellular signaling events and pax6 transcription regulation in growth factor-mediated proliferation. In corneal epithelial cells, this suggests that inhibition of pax6 expression is a prerequisite for EGF to elicit controls of cell growth and fate. [ABSTRACT FROM AUTHOR]

• 3D nanoflowers composed of LDH nanosheets are spontaneously grown on AC. • A capacitance of 947F g−1 at 1 A g−1 were obtained by NiCo LDH/AC electrodes. • The supercapacitor device shows high energy density of 39.7 Wh kg−1. • The capacitance retention of supercapacitor device is 80% after 5000 cycles. Hierarchical Porous N doped AC@ Nickel–Cobalt Layered Double Hydroxide Composites for Asymmetric Supercapacitor Applications ga1 Nitrogen-doped activated biocarbon (AC) and nickel-cobalt layered double hydroxides (LDHs) composites (Ni x Co 1−x LDH/AC) are prepared by solvothermal method at various Ni/Co molar ratios. 3D nanoflowers composed of LDH nanosheets are spontaneously grown on the surface of AC from bio-waste, providing a suitable structure for the diffusion and transport of electrolyte ions. Ni 0.5 Co 0.5 LDH/AC composite electrode has high specific capacitance of 947 F g−1 at the current density of 1 A g−1, which could be explained by the synergistic effect of LDHs and AC. Furthermore, symmetric coin-cell AC//Ni 0.5 Co 0.5 LDH/AC supercapacitor is assembled using Ni 0.5 Co 0.5 LDH/AC composite as the cathode, and the pristine AC as the anode. Within 1.6 V voltage range, the supercapacitor device shows a maximum capacitance values (C sc) of 112 F g−1 at 1 A g−1. The developed asymmetric supercapacitor exhibits excellent rate performance and good cycle stability reflected through the maintenance of 80% of the initial C sc after 5000 consecutive cycles. Moreover, high energy density (39.7 Wh kg−1) is observed at low power density of 0.8 kW kg−1, and maintained at relatively high value (22.2 Wh kg−1) at high power density (16 kW kg−1). All these data indicate the potential applicability of AC//Ni 0.5 Co 0.5 LDH/AC asymmetric supercapacitor for energy storage. [ABSTRACT FROM AUTHOR]

Focus on the safety of herbal medicines has mainly been directed towards the presence of intrinsic toxicity, as found in the cases of renal and hepatic dysfunction caused by aristolochic acids. However, contamination from extrinsic hazards may impart an even greater reduction in their safety and efficacy. This study reveals that pesticides were present in the majority (88%) of a comprehensive cross-section (n = 1771) of herbal medicine samples. Alarmingly, more than half (59%) contained pesticides over the European Pharmacopoeia (EP) limit, and 43% of them contained 35 varieties of banned, extremely toxic pesticides, eight of which were detected at levels over 500 times higher than the default Maximum Residue Limit (MRL). DDTs, carbofuran, and mevinphos were confirmed as being among the most risk-inducing pesticides by three different risk assessment methods, reported to produce carcinogenic, genotoxic, reproductive, and developmental effects, in addition to carrying nephrotoxicity and hepatotoxicity. In light of these findings, and withstanding that extrinsic hazards can be controlled unlike intrinsic toxicity, the authors here strongly recommend the application of herbal medicine quality-control measures and solutions to safeguard against a neglected but certainly potentially serious health risk posed to the majority of the global population that consumes herbal medicines. Image 1 • Extrinsic contamination in herbal medicines is severe with extremely toxic and banned pesticides detected. • DDTs, carbofuran, and mevinphos were confirmed as the most risk-inducing pesticides. • Crataegi fructus posed most serious risks, while pesticides were most widely detected in radix & rhizoma. • A globalized and regulated solution for surveilling, monitoring, and certifying the HM supply chain is in urgent need. [ABSTRACT FROM AUTHOR]

Compared with other crops, peanut planting costs are lower, and it is very drought-tolerant, and can obtain better benefits. In this paper, 16 peanut varieties were selected, and drought resistance tests were carried out at the flowering and cutting stage under water stress conditions. The root characteristics related to drought resistance of peanuts and the physiological mechanism of drought resistance of different varieties were studied to screen peanut varieties with better drought resistance. According to the relative value (RV) of each trait, the drought resistance coefficient (DC) and drought resistance are calculated. The results show that A596, NC6, Shanhua11 and shanhua7 have strong drought resistance, Shanhua12, Nongda 818, Shanhua 8, Huayu 20, Haihua 1, 79266, Shanhua 9, Hua 17 have moderate drought resistance, while Jihua 4, Guihua 836 , ICG6848 and Baisha1016 have weaker drought resistance. [ABSTRACT FROM AUTHOR]

[Display omitted] • k values relating to nitro-TP formation in the model were determined using DFT. • Multiple mechanisms for nitro-TP formation in SR-AOPs are clearly elucidated. • DFT-based model evidently improves the prediction accuracy of nitro-TP profiles. Kinetic models are widely employed to investigate the reaction mechanisms and estimate kinetic parameters of advanced oxidation processes (AOPs), which are critical for assessing toxicity variations in these processes. However, conventional models often oversimplify the kinetics related to transformation products (TPs) due to the complex reactions involved in AOPs. Consequently, predicting the concentration profiles of TPs in conventional kinetic models is challenging. In this study, we aimed to overcome this challenge by developing a novel kinetic model that enriches the TPs-related elementary reactions in AOPs. Specifically, we mapped the entire reaction pathways from parent organic compounds through various intermediates to their TPs using density functional theory (DFT). We investigated the formation of nitro-TPs of phenolics, such as salicylic acid, hydroxybenzoic acid, phenol and 4-chlorophenol in sulfated radical-based AOPs in the presence of NO 2 −. The predicted concentrations of nitro-TPs obtained from our model exhibited a close match with those reported in previous research, thus confirming the accuracy of our predictions. Our research highlights the effectiveness of combining DFT and kinetic modeling, which facilitates a streamlined understanding of the mechanisms governing TP formation and decay in AOPs. This approach holds the potential to advance our comprehension of these complex reactions and may be beneficial in future studies of similar reactions. [ABSTRACT FROM AUTHOR]

Synergistically enhancing and realizing the value of grassland ecosystem services (ES) for economic activity is an important but challenging task for achieving sustainability in the karst desertification control (KDC). However, how to use grassland ES value characteristics in the KDC to make decisions on ES improvement, human well-being enhancement, and sustainable development remains unclear. In this paper, we took the contiguous region of karst desertification in Yunnan-Guangxi-Guizhou, China, a global hotspot, as the study area. Based on the valuation of the gross ecosystem product (GEP) and county economic intensity, we analyzed the structural and spatial characteristics of grassland GEP in the KDC using spatial analysis methods. We found that: (1) the grassland GEP in the KDC is mainly distributed in counties with low economic intensity (86.05% of the total number of counties) and vulnerable to losses caused by the livelihood of farmers; (2) the grassland GEP in the KDC is spatially small and scattered (the geographic concentration lies between 0.015 and 0.237), which makes it difficult to form industrial scale advantages; (3) the public product index (66.22–96.77%) and industry scale concentration (97.87–99.86%) of grassland GEP in the KDC are high, and most of the GEP is difficult to transform on the private market. Based on our findings, we proposed three corresponding recommendations for economic decision-making. The results of this study can provide a reference for economic decision-making regarding the management of grassland ES in karst areas with similar conditions and beyond. [ABSTRACT FROM AUTHOR]

A series of 4-bromo-N-(3,5-dimethoxyphenyl)benzamide derivatives were designed and synthesised as novel fibroblast growth factor receptor-1 (FGFR1) inhibitors. We found that one of the most promising compounds, C9, inhibited five non-small cell lung cancer (NSCLC) cell lines with FGFR1 amplification, including NCI-H520, NCI-H1581, NCI-H226, NCI-H460 and NCI-H1703. Moreover, the IC50 values for the compound C9 were 1.36 ± 0.27 µM, 1.25 ± 0. 23 µM, 2.31 ± 0.41 µM, 2.14 ± 0.36 µM and 1.85 ± 0.32 µM, respectively. The compound C9 arrested the cell cycle at the G2 phase in NSCLC cell lines. The compound C9 also induced cellular apoptosis and inhibited the phosphorylation of FGFR1, PLCγ1 and ERK in a dose-dependent manner. In addition, molecular docking experiments showed that compound C9 binds to FGFR1 to form six hydrogen bonds. Taken together, our data suggested that the compound C9 represented a promising lead compound-targeting FGFR1. [ABSTRACT FROM AUTHOR]

Background Nasopharyngeal carcinoma (NPC) is closely associated with genetic factors and Epstein-Barr virus infection, showing strong familial aggregation. Individuals with a family history suffer elevated NPC risk, requiring effective genetic counseling for risk stratification and individualized prevention. Methods We performed whole-exome sequencing on 502 familial NPC patients and 404 unaffected relatives and controls. We systematically evaluated the established cancer predisposition genes and investigated novel NPC susceptibility genes, making comparisons with 21 other familial cancers in the UK biobank (N = 5218). Results Rare pathogenic mutations in the established cancer predisposition genes were observed in familial NPC patients, including ERCC2 (1.39%), TP63 (1.00%), MUTYH (0.80%), and BRCA1 (0.80%). Additionally, 6 novel susceptibility genes were identified. RAD54L , involved in the DNA repair pathway together with ERCC2 , MUTYH , and BRCA1 , showed the highest frequency (4.18%) in familial NPC. Enrichment analysis found mutations in TP63 were enriched in familial NPC, and RAD54L and EML2 were enriched in both NPC and other Epstein-Barr virus–associated cancers. Besides rare variants, common variants reported in the studies of sporadic NPC were also associated with familial NPC risk. Individuals in the top quantile of common variant-derived genetic risk score while carrying rare variants exhibited increased NPC risk (odds ratio = 13.47, 95% confidence interval = 6.33 to 28.68, P  =   1.48 × 10–11); men in this risk group showed a cumulative lifetime risk of 24.19%, much higher than those in the bottom common variant-derived genetic risk score quantile and without rare variants (2.04%). Conclusions This study expands the catalog of NPC susceptibility genes and provides the potential for risk stratification of individuals with an NPC family history. [ABSTRACT FROM AUTHOR]

The processing and analysis of massive high-dimensional datasets are important issues in precision livestock farming (PLF). This study explored the use of multivariate analysis tools to analyze environmental data from multiple sensors located throughout a broiler house. An experiment was conducted to collect a comprehensive set of environmental data including particulate matter (TSP, PM 10 , and PM 2.5), ammonia, carbon dioxide, air temperature, relative humidity, and in-cage and aisle wind speeds from 60 locations in a typical commercial broiler house. The dataset was divided into 3 growth phases (wk 1–3, 4–6, and 7–9). Spearman's correlation analysis and principal component analysis (PCA) were used to investigate the latent associations between environmental variables resulting in the identification of variables that played important roles in indoor air quality. Three cluster analysis methods; k-means, k-medoids, and fuzzy c-means cluster analysis (FCM), were used to group the measured parameters based on their environmental impact in the broiler house. In general, the Spearman and PCA results showed that the in-cage wind speed, aisle wind speed, and relative humidity played critical roles in indoor air quality distribution during broiler rearing. All 3 clustering methods were found to be suitable for grouping data, with FCM outperforming the other 2. Using data clustering, the broiler house spaces were divided into 3, 2, and 2 subspaces (clusters) for wk 1 to 3, 4 to 6, and 7 to 9, respectively. The subspace in the center of the house had a poorer air quality than other subspaces. [ABSTRACT FROM AUTHOR]

An in situ experiment was designed in which Potamogeton crispus and Hydrilla verticillata were planted in plastic pots 25, 50, 75, 100, 125, 150, 175 and 200 cm underwater to study the effect of water depth on the growth and photosynthetic fluorescence characteristics of the two submerged macrophytes in Lake Gehu, China. The results showed that: 1) Water depth had no significant effect on the germination of both submerged macrophytes. The final germination rate of P. crispus turions was higher than 80%, and the final germination rate of the H. verticillata winter buds was 100%; 2) Water depth affected the survival rate of both submerged macrophytes, and the seedlings at depths of 150, 175 and 200 cm all eventually died; 3) Water depth altered the morphological characteristics of P. crispus and H. verticillata seedlings. (4) Increasing water depth significantly affected biomass (p <.05), with the biomass initially tending to increase, but then decreasing. The root to shoot ratio of both submerged macrophytes decreased with increasing water depth; 5) Chlorophyll contents of P. crispus and H. verticillata increased with water depth from 25 to 150 cm; 6) Water depth had an obvious effect on the photosynthetic fluorescence of submerged macrophytes. The Fv/Fm increased slightly from water depths from 25 to 75 cm, and then decreased significantly when water depth exceeded 100 cm. The ETRmax was significantly different among all treatment groups, and ETRmax was obviously higher at water depths of 25 and 50 cm than at all other depths. These results showed that submerged macrophytes have a limited water depth tolerance range. In Lake Gehu, the recovery of submerged macrophytes will be better in areas with water depths less than 125 cm. [ABSTRACT FROM AUTHOR]

Epigenetic factor CCCTC binding factor (CTCF) plays important roles in the genetic control of cell fate. Previous studies found that CTCF is positively and negatively regulated at the transcriptional level by epidermal growth factor (EGF) and ultraviolet (UV) stimulation, respectively. However, it is unknown whether other stresses modify the CTCF protein. Here, we report that regulation of CTCF by de-SUMOylation is dependent upon hypoxic and oxidative stresses. We found that stimulation of human corneal epithelial cells with hypoxic stress suppressed a high molecular mass form of CTCF (150 kDa), but not a lower molecular weight form of CTCF (130 kDa). Further investigation revealed that the hypoxic stress-suppressed 150- kDa CTCF was a small ubiquitin-related modifier (SUMO)-ylated form of the protein. Hypoxic stress-induced de-SUMOylation of human CTCF was associated with lysine 74 and 689 residues, but not to the phosphorylation of CTCF. Overexpression of SENP1 induced de-SUMOylation of CTCF. However, knockdown of SENP1 could not rescue hypoxic stress-induced CTCF de-SUMOylation. Overexpression of SUMO1 and SUMO2 increased SUMOylation of CTCF and partially blocked hypoxic stress-induced CTCF de-SUMOylation, suggesting that free cellular SUMO proteins play roles in regulating hypoxia-induced CTCF de-SUMOylation. In addition, hypoxic stress significantly inhibited PAX6 mRNA and protein expressions by suppression of PAX6-P0 promoter activity. The result was further supported by data showing that knockdown of CTCF significantly enhanced expression of PAX6 and abolished hypoxia-induced suppression of PAX6. Thus, we conclude that hypoxic stress induces de-SUMOylation of CTCF to functionally regulate CTCF activity. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein kinase (MAPK) cascades play important roles in mediating pathogen responses and reactive oxygen species signaling. In plants, MAPKs are classified into four major groups (A-D). Previous studies have mainly focused on groups A and B, but little is known about group C. In this study, we functionally characterized a stress-responsive group C MAPK gene ( GhMPK2) from cotton. Northern blot analysis indicated that GhMPK2 was induced not only by signaling molecules, such as ethylene and methyl jasmonate, but also by methyl viologen-mediated oxidative stress. Transgenic tobacco ( Nicotiana tabacum) plants that overexpress GhMPK2 displayed enhanced resistance to fungal and viral pathogens, and the expression of the pathogenesis-related (PR) genes, including PR1, PR2, PR4, and PR5, was significantly increased. Interestingly, the transcription of 1-aminocyclopropane-1-carboxylic acid synthase ( ACS) and 1-aminocyclopropane-1-carboxylic acid oxidase ( ACO) was significantly upregulated in transgenic plants, suggesting that GhMPK2 positively regulates ethylene synthesis. Moreover, overexpression of GhMPK2 elevated the expression of several antioxidant enzymes, conferring on transgenic plants enhanced reactive oxygen species scavenging capability and oxidative stress tolerance. These results increased our understanding of the role of the group C GhMPK2 gene in multiple defense-signaling pathways, including those that are involved in responses to pathogen infection and oxidative stress. In this study, functional characterization of a cotton group C mitogen-activated protein kinase (MAPK) gene ( GhMPK2) was carried out. The expression of GhMPK2 was induced by signaling molecules and oxidative stress. Overexpression of GhMPK2 significantly elevated the expression of the pathogenesis-related ( PR), signaling-related and antioxidative genes, and thereby enhanced the transgenic plants disease resistance and oxidative stress tolerance. [ABSTRACT FROM AUTHOR]

Polo-like kinase 3 (Plk3) activation occurs after exposure to environmental or genotoxic stresses. Plk3 regulates cell fate through regulating cell cycle progression. UV irradiation is one of the major environmental stresses that affect corneal epithelial wound healing. In the present study, we report that UV irradiation activated Plk3 and that Plk3 interacts with AP-1 and c-Jun, which appears to be important to mediate corneal epithelial cell apoptosis after UV irradiation. Recombinant Plk3, as well as Plk3 immunoprecipitated from UV-irradiated cells, phosphorylated c-Jun in vitro. The phosphorylation of c-Jun by Plk3 immunoprecipitates was not altered by the pre-removal of JNK from the cell lysates. In addition, the effect of UV irradiation-induced phosphorylation of c-Jun and apoptosis were not significantly affected by knockdown of JNK mRNA. Co-immunoprecipitation reveals that Plk3 and c-Jun directly interacted with each other. Consistently, Plk3 co-localized with c-Jun to the nucleus after UV irradiation. Further, modulating Plk3 activities by overexpressing Plk3 or its mutants significantly affected UV irradiation-induced c-Jun activity and subsequent apoptosis. Our results thus provide for the first time that Plk3 mediates UV irradiation-induced c-Jun activation by phosphorylating c-Jun, suggesting that Plk3 plays an important role in mediating programmed cell death of corneal epithelial cells after UV irradiation. [ABSTRACT FROM AUTHOR]

Recent studies from our lab found that ultraviolet (UV) irradiation induces a voltage-gated potassium (Kv) channel activation and subsequently activates JNK signaling pathway resulting in apoptosis. The present study in rabbit corneal epithelial (RCE) cells is to investigate mechanisms of UV irradiation-induced Kv channel activity involving p53 activation in parallel to DNA damage-induced signaling pathway. UV irradiation-induced signaling events were characterized by measurements of JNK activation and further downstream p53 phosphorylation. UV irradiation elicited an early response in the cell membrane through activation of Kv channels to activate the JNK signaling pathway and p53 phosphorylation. Exposure of RCE cells to UV irradiation within a few min resulted in JNK and p53 activations that were markedly inhibited by suppression of Kv channel activity. However, suppression of Kv channel activity failed to prevent p53 activation induced by extended DNA damages through prolonging UV exposure time (more than 15?min). In addition, caffeine inhibited UV-induced activation of SEK, an upstream MAPK kinase of JNK, resulting in suppression of both Kv channel-involved and DNA damage-induced p53 activation. Our results indicate in these cells that UV irradiation induces earlier and later intracellular events that link to activation of JNK and p53. The early event in response to UV irradiation is initiated by activating Kv channels in the cell membrane, and the later event is predominated by UV irradiation-caused DNA damage.Oncogene (2005) 24, 3020-3027. doi:10.1038/sj.onc.1208547 Published online 7 March 2005 [ABSTRACT FROM AUTHOR]

CCCTC binding factor (CTCF), a transcriptional regulator, plays important roles in epigenetics and development. In the present study, we report that overexpression of CTCF in transgenic mice during embryonic development suppresses Pax6 gene expression. This effect causes defects in ocular development that result in microophthalmia. In eye-derived cells transfected with a tetracycline turn-on CTCF system, up-regulation of CTCF expression significantly suppressed Pax6 expression. In contrast, the knockdown of CTCF mRNA resulted in the down-regulation of CTCF protein expres- sion, which in turn enhanced the Pax6 expression. CTCF controls Pax6 transcription by interacting with a re- pressor element located in the 5′-flanking region up- stream of the Pax6 P0 promoter. This interaction sup- pressed Pax6 gene transcription by blocking the effect of an ectoderm enhancer located 3.5 kb upstream from the P0 promoter. We also found an 80-bp sequence in a region -1.2 kbp upstream from the P0 promoter that contained multiple CTCF binding sites and interacted with nuclear proteins obtained from eye-derived cells forming electrophoretic mobility shift assay complexes with CTCF. We conclude that a novel function of CTCF is to regulate Pax6 transcription by binding to the repressor element, which in turn blocks the effect of the ectoderm enhancer resulting in the inhibition of P0 promoter activity. [ABSTRACT FROM AUTHOR]

GPAT, the rate-limiting enzyme in triacylglycerol (TAG) synthesis, plays an important role in seed oil accumulation. In this study, two AhGPAT9 genes were individually cloned from the A- and B- genomes of peanut, which shared a similarity of 95.65%, with 165 site differences. The overexpression of AhGPAT9 or the knock-down of its gene expression increased or decreased the seed oil content, respectively. Allelic polymorphism analysis was conducted in 171 peanut germplasm, and 118 polymorphic sites in AhGPAT9A formed 64 haplotypes (a1 to a64), while 94 polymorphic sites in AhGPAT9B formed 75 haplotypes (b1 to b75). The haplotype analysis showed that a5, b57, b30 and b35 were elite haplotypes related to high oil content, whereas a7, a14, a48, b51 and b54 were low oil content types. Additionally, haplotype combinations a62/b10, a38/b31 and a43/b36 were associated with high oil content, but a9/b42 was a low oil content haplotype combination. The results will provide valuable clues for breeding new lines with higher seed oil content using hybrid polymerization of high-oil alleles of AhGPAT9A and AhGPAT9B genes. [ABSTRACT FROM AUTHOR]

A compressive pre-straining of 0.05 was applied to two Mg–2Y alloy sheets with different initial textures along their normal directions. Creep behaviors of these sheets before and after the pre-straining were investigated at 493 K under stresses ranging from 20 to 100 MPa. The influence of pre-straining on creep behaviors was then discussed. The results show that the effects of pre-straining on creep behaviors of the two sheets are quite different. A profound strengthening effect of this pre-straining is observed on the creep resistance of the extruded sheet with creep strain decreased by half and steady strain rate reduced by 75% at most. By contrast, for the rolled sheet, the improvement of creep resistance by the pre-straining is negligible. The difference lies in the number of anomalous twins introduced by the pre-straining. After the pre-straining, considerable {10–12} anomalous twins have been introduced in the extruded sheet with a random initial texture, compared to the rolled one. Dislocation movements during the creep can be impeded by the large amounts of twins in the pre-strained extruded sheets, resulting in the obvious improved creep resistance. Meanwhile, different predominant dislocation mechanisms are found along different creep directions. Since a more excellent impeding effect of the twins is obtained on cross-slip, better improvement of the creep resistance can be achieved along the TD than along the ED of the pre-strained extruded sheet. • Pre-straining is successfully applied to Mg–2Y extruded and rolled sheets. • Anomalous twins are induced in the grains which have high activities for basal slip. • Considerable anomalous twins are induced in extruded sheet compared to rolled sheet. • Strong impeding effect of anomalous twins on dislocations enhances creep resistance. • Dislocations induced by work hardening have limited benefits for creep resistance. [ABSTRACT FROM AUTHOR]

Aim: Norcantharidin (NCTD) has been used as a clinical antineoplastic drug in China for several years, and diamminedichloroplatinum is a valuable clinical cancer chemotherapy agent. Here, we tried to investigate the effects of NCTD plus diamminedichloroplatinum on hepatic carcinoma in murine.Materials and Methods: In vivo and in vitro investigations on anticancer effects of the two drugs were individually made.Result: In vitro, the combination of the two drugs resulted in apparent apoptosis and cell proliferation inhibitions of H22 cancer cells. Meanwhile, their coadministration in vivo produced significant suppressions of tumor growth and cancerometastasis. Further, CD31 immunohistochemistry and matrigel tube formation assay demonstrated that angiogenesis was inhibited by NCTD plus diamminedichloroplatinum in vivo and in vitro, respectively.Conclusion: Based on the findings, we concluded that NCTD plus diamminedichloroplatinum may have an additive anticancer efficacy because the two drugs work in different ways, and thus, their combination had inhibited cancer cell proliferations and tumor angiogenesis more effectively than either of the compounds alone. [ABSTRACT FROM AUTHOR]

Background: Diosgenin, mainly extracted from wild diosgenin-contained Dioscorea species, is a well-known starting material of steroidal and contraceptive drugs. However, due to large market demand and increasingly ecological damage, wild Dioscorea species resources available have been gradually declining. Therefore, identification of new potential ecological distribution of diosgenin-contained Dioscorea species is necessary for diosgenin production. Methods: In this study, a large occurrence dataset (1808 data points) of diosgenin-contained Dioscorea species was obtained from Eastern Asia, Southern North America and Southern Africa. Along with the data for six critical environmental parameters and one soil factor, Geographic Information System for Global Medicinal Plant was applied to predict the potential suitable distribution of Dioscorea species. Results: The results showed that the potential distribution of these Dioscorea species covered a wide field, and that new ecological suitability areas were mainly distributed in the central region of South America, the southern part of the European and coastal region of Oceania. Jackknife test indicated that annual precipitation and annual mean radiation were the important climatic factors controlling the distribution of Dioscorea species. Conclusions: The suitable areas and critical climatic factors will serve as a useful guide for diosgenin-contained Dioscorea species conservation and cultivation in ecological suitable areas. [ABSTRACT FROM AUTHOR]

Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response. [ABSTRACT FROM AUTHOR]

At present, the instability of floor roadway is increasingly serious, and even the representative high-performance U-steel support cannot provide roadways with completely effective support. Thus, the mechanism of roadway deformation should be analyzed rather than only considering the roadway support. To study the influence of coal mining on the stability of floor roadways under tectonic stress, taking the floor roadway under No.8 coal seam in Luling Coal Mine in China as the research object, the roadway deformation was tested with and without tectonic stress through the similar physical simulation method. Finally, the changing mechanisms of the stress field, fracture development and displacement field of the surrounding rocks in the floor roadway under mining effects were systematically analyzed. The results show that: (1) under the same stress condition, deformation and fracture of the floor roadway increase with the increase of mining step; (2) without tectonic stress, the maximum hoop stress of the floor roadway arch foot is 32.5 MPa located 2.7 m away from the roadway wall. Meanwhile, under tectonic stress, the maximum stress changes to 38.5 MPa at 3.6 m away from the roadway wall; (3) whether under mining effects or not, the deformation time is longer and deformation failure is larger under tectonic stress. The conclusions indicate the tectonic stress field has significant on roadway deformation and failure, which can provide the technical reference for the optimization of mine roadway layout. [ABSTRACT FROM AUTHOR]

Hypoxic conditions in the cornea affect epithelial function by activating Polo-like kinase 3 (Plk3) signaling and the c-Jun-AP-1 transcription complex, resulting in apoptosis of corneal epithelial cells. Hypoxic stress in the culture conditions also regulates limbal stem cell growth and fate. In this study, we demonstrate that there is a differential response of Plk3 in hypoxic stressinduced primary human limbal stem (HLS) and corneal epithelial (HCE) cells, resulting in different pathways of cell fate. We found that hypoxic stress induced HLS cell differentiation by down-regulating Plk3 activity at the transcription level, which was opposite to the effect of hypoxic stress on Plk3 activation to elicit HCE cell apoptosis, detected by DNA fragmentation and TUNEL assays. Hypoxic stress-induced increases in c-Jun phosphorylation/ activation were not observed in HLS cells because Plk3 expression and activity were suppressed in hypoxia-induced HLS cells. Instead, hypoxic stress-induced HLS cell differentiation was monitored by cell cycle analysis and measured by the decrease and increase in p63 and keratin 12 expression, respectively. Hypoxic stress-induced Plk3 signaling to regulate c-Jun activity, resulting in limbal stem cell differentiation and center epithelial apoptosis, was also found in the corneas of wild-type and Plk3-/--deficient mice. Our results, for the first time, reveal the differential effects of hypoxic stress on Plk3 activity in HLS and HCE cells. Instead of apoptosis, hypoxic stress suppresses Plk3 activity to protect limbal stem cells from death and to allow the process of HLS cell differentiation. [ABSTRACT FROM AUTHOR]

Chan Ding training is beneficial to health and emotional wellbeing. More and more people have taken up this practice over the past few years. A major training method of Chan Ding is to focus on the ten Mailuns, i.e., energy points, and to maintain physical stillness. In this article, wireless wearable accelerometers were used to detect physical stillness, and the created physical stillness index (PSI) was also shown. Ninety college students participated in this study. Primarily, accelerometers used on the arms and chest were examined. The results showed that the PSI values on the arms were higher than that of the chest, when participants moved their bodies in three different ways, left-right, anterior-posterior, and hand, movements with natural breathing. Then, they were divided into three groups to practice Chan Ding for approximately thirty minutes. Participants without any Chan Ding experience were in Group I. Participants with one year of Chan Ding experience were in Group II, and participants with over three year of experience were in Group III. The Chinese Happiness Inventory (CHI) was also conducted. Results showed that the PSI of the three groups measured during 20–30 min were 0.123 ± 0.155, 0.012 ± 0.013, and 0.001 ± 0.0003, respectively (p < 0.001 ***). The averaged CHI scores of the three groups were 10.13, 17.17, and 25.53, respectively (p < 0.001 ***). Correlation coefficients between PSI and CHI of the three groups were −0.440, −0.369, and −0.537, respectively (p < 0.01 **). PSI value and the wearable accelerometer that are presently available on the market could be used to evaluate the quality of the physical stillness of the participants during Chan Ding practice. [ABSTRACT FROM AUTHOR]

Epidermal growth factor (EGF) plays an important role in corneal epithelial migration and proliferation to improve the wound healing process. This study aimed to understand the role of NFκB in EGF-induced corneal epithelial wound healing through regulation of CTCF activity, which plays important roles in cell motility and migration to promote wound healing. The effect of NFκB p50 on corneal epithelial wound healing was investigated by comparing the eyes of wild-type and p50 knock-out mice. We found that there was a significant retardation in corneal epithelial wound healing in the corneas of p50 knockout mice. Wound closure rates were measured in human corneal epithelial cells transfected with an NFκB activation-sensitive CTCF expression construct to demonstrate the effect of human CTCF expression under the control of EGF-induced NFκB activation on wound healing. EGF stimulation activated NFκB, which directly triggered the expression of the exogenous human CTCF in transfected cells and, subsequently, promoted human corneal epithelial cell motility, migration, and wound healing. Overexpression of CTCF in corneal epithelial cells and mouse corneas significantly enhanced the wound healing process. Furthermore, the effect of over expressing NFκB p50 in corneal epithelial cells on the promotion of wound healingwas abolished by knockdown of CTCF with CTCF-specific shRNA. Thus, a direct regulatory relationship between EGF-induced NFκB p50 and CTCF activation affecting corneal epithelial wound healing has been established, indicating that CTCF is, indeed, a NFκB p50-targeted and effective gene product in the core transcriptional network downstream from the growth factor-induced NFκB signaling pathway. [ABSTRACT FROM AUTHOR]

SALL4 is a transcription factor that plays a key role in the maintenance and self-renewal of embryonic stem cells and hematopoietic stem cells. Given that little is known about regulation of SALL4, we studied biochemical modifications of SALL4B, a major splicing variant of SALL4, and elucidated their biological function. SALL4B was primarily modified by ubiquitination when it was expressed in both Sf9 and HEK293T cells. A significant fraction of SALL4B was further modified by sumoylation when it was expressed in HEK293T cells. Constitutive SUMO-modification of SALL4B was also detected in Tera-1, a cell line of the teratocarcinoma origin. SALL4B sumoylation was independent of ubiquitination and lysine residues 156, 316, 374, and 401 were essential for sumoylation. Chromatin fraction contained more SUMO-deficient SALL4B. Despite a shorter half-life than the wild-type counterpart, SUMO deficient SALL4B interacted with OCT4 more efficiently than the wild-type SALL4B. RNAi-mediated silencing of SALL4 expression caused significant down-regulation of both OCT4 and SOX2, which was rescued by ectopic expression of SALL4B but not by SUMO-deficient mutant. Significantly, compared with the wildtype SALL4B, SUMO-deficient mutant exhibited compromised trans-activation or trans-repression activities in reporter gene assays. Combined, our studies reveal sumoylation as a novel form of post-translational modification for regulating the stability, subcellular localization, and transcriptional activity of SALL4. [ABSTRACT FROM AUTHOR]

Pax6 plays an important role in embryonic cell (ES) differentiation during embryonic development. Expression of Pax6 undergoes from a low level to high levels following ES cell differentiation to neural stem cells, and then fades away in most of the differentiated cell types. There is a limited knowledge concerning how Pax6 is regulated in ES cell differentiation. We report that Pax6 expression in mouse ES cells was controlled by CCCTC binding factor (CTCF) through a promoter repression mechanism. Pax6 expression was significantly enhanced while CTCF activity was kept in the constant during ES cell differentiation to radial glial cells. Instead, the interaction of CTCF with Pax6 gene was regulated by decreased CTCF occupancy in its binding motifs upstream from Pax6 P0 promoter following the course of ES cell differentiation. Reduced occupancy of CTCF in the binding motif region upstream from the P0 promoter was due to increased DNA methylations in the CpG sites identified in the region. Furthermore, changes in DNA methylation levels in vitro and in vivo effectively altered methylation status of these identified CpG sites, which affected ability of CTCF to interact with the P0 promoter, resulting in increases in Pax6 expression. We conclude that there is an epigenetic mechanism involving regulations of Pax6 gene during ES cell differentiation to neural stem cells, which is through increases or decreases in methylation levels of Pax6 gene to effectively alter the ability of CTCF in control of Pax6 expression, respectively. [ABSTRACT FROM AUTHOR]