Supershear triggering and cascading fault ruptures of the 2023 Kahramanmaras, Türkiye, earthquake doublet.

On 6 February 2023, two large earthquakes (moment magnitude 7.8 and 7.6) shocked a vast area of southeastern Türkiye and northern Syria, leading to heavy casualties and economic loss. To investigate the rupture process over multiple fault segments, we performed a comprehensive analysis of local seismic and geodetic data and determined supershear ruptures on the initial branch and the Pazarcik and Erkenek segments and subshear ruptures on the Amanos segment of event 1. The bilateral rupture of event 2 also presents distinct sub- and supershear velocities. The dynamic stress of the branch fault rupture triggered the Pazarcik segment initial rupture at a point 9 kilometers west of the junction of these two faults, boosting the supershear rupture of the Pazarcik segment of the main fault. The geometry and prestress level of multiple segments controlled the rupture behaviors and influenced the ground shaking intensity.

Disturbance of consciousness caused by dyclonine hydrochloride mucilage: a case report.

BACKGROUND: Dyclonine hydrochloride mucilage is a topical anaesthetic formulated for mucosal surfaces. It is employed frequently for topical anaesthesia of the pharynx prior to endoscopic examinations such as electronic gastroscopy, and few adverse reactions have been reported. This article describes a patient who experienced a transient but severe disturbance of consciousness following oral dyclonine hydrochloride mucilage administration. CASE PRESENTATION: A 75-year-old female presenting with gastrointestinal bleeding was examined by electronic gastroscopy. Six minutes after oral dyclonine hydrochloride mucilage administration, the patient entered a comatose-like state accompanied by loss of limb muscle tone and profuse perspiration. This response was not accompanied by changes in cardiac rhythm, blood pressure, or respiration rate, suggesting an effect on higher brain centres. After ten minutes, the patient's symptoms were alleviated. CONCLUSION: We suggest that sites of dyclonine hydrochloride mucilage use be equipped with appropriate rescue devices for these rare events.

The Effectiveness of Narrative Therapy in Reducing Work Pressure and Improving Health Behavior Among Anesthesia Clinical Frontline Nurses.

Objectives: The aim of this study was to investigate the effectiveness of narrative therapy in reducing work pressure and improving health behavior among clinical and anesthesia frontline nurses. Methods: We used convenience sampling to select clinical and anesthesiology department nurses from hospitals between May 2019 and May 2021. We used a nursing knowledge-attitude-behavior questionnaire to assess the status of nurses and assess the effectiveness of the narrative therapy intervention. We analyzed our data using SPSS and Smart PLS. Results: We found statistically significant differences in scores on the Competence Scale (NCS) and the Nursing Caring Characters Assessment Tool (NCCAT) (p<.05). The average scores of items in each dimension of clinical and anesthesiology department narrative nursing knowledge and behavior were: knowledge score (3.67±0.52), attitude score (5.48±0.62), and behavior score (4.74±0.77). Conclusion: The ADDIE-based narrative nursing training program improved nurses' narrative nursing ability and humanistic care quality, reducing work pressure and promoting health behavior. These findings highlight the importance of narrative therapy in clinical practice for frontline nurses.

Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

LINC00629, a KLF10-responsive lncRNA, promotes the anticancer effects of apigenin by decreasing Mcl1 stability in oral squamous cell carcinoma.

Apigenin, a naturally occurring flavonoid, is known to exhibit antitumor activity in many cancers. However, the regulatory mechanism of apigenin and the long noncoding RNAs (lncRNAs) altered upon apigenin treatment in oral squamous cell carcinoma (OSCC) remain unclear. In this study, we found that LINC00629 was significantly upregulated in response to apigenin treatment. Upregulated LINC00629 enhanced the growth-suppressive and proapoptotic effects of apigenin on OSCC cells by interacting with Mcl1 and facilitating its degradation. Subsequently, our data indicated that KLF10, an important transcription factor, directly bound to the promoter of LINC00629, facilitating its transcription and contributing to apigenin-induced LINC00629 expression. Collectively, these results suggest that the KLF10-LINC00629-Mcl1 axis plays an important role in the anticancer effects of apigenin.

Phenylalanine suppresses cell death caused by loss of fumarylacetoacetate hydrolase in Arabidopsis.

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of Tyrosine (Tyr) degradation pathway essential to animals and the deficiency of FAH causes an inborn lethal disease. In plants, a role of this pathway was unknown until we found that mutation of Short-day Sensitive Cell Death1 (SSCD1), encoding Arabidopsis FAH, results in cell death under short day. Phenylalanine (Phe) could be converted to Tyr and then degraded in both animals and plants. Phe ingestion in animals worsens the disease caused by FAH defect. However, in this study we found that Phe represses cell death caused by FAH defect in plants. Phe treatment promoted chlorophyll biosynthesis and suppressed the up-regulation of reactive oxygen species marker genes in the sscd1 mutant. Furthermore, the repression of sscd1 cell death by Phe could be reduced by α-aminooxi-ß-phenylpropionic acid but increased by methyl jasmonate, which inhibits or activates Phe ammonia-lyase catalyzing the first step of phenylpropanoid pathway, respectively. In addition, we found that jasmonate signaling up-regulates Phe ammonia-lyase 1 and mediates the methyl jasmonate enhanced repression of sscd1 cell death by Phe. These results uncovered the relation between chlorophyll biosynthesis, phenylpropanoid pathway and jasmonate signaling in regulating the cell death resulting from loss of FAH in plants.

Rupture process of the 2021 M7.4 Maduo earthquake and implication for deformation mode of the Songpan-Ganzi terrane in Tibetan Plateau.

The deformation mode of the Tibetan Plateau is of crucial importance for understanding its construction and extrusion processes, as well as for the assessment of regional earthquake potential. Block motion and viscous flow models have been proposed to describe the deformation field but are not fully supported by modern geophysical observations. The 2021 Mw 7.4 Maduo earthquake, which occurred inside the Songpan-Ganzi terrane (SGT) in central-east Tibet, provides a chance to evaluate the associated deformation mode of the region. We conduct a joint inversion for this earthquake and resolve a bilateral rupture process, which is characterized by super- and subshear rupture velocities, respectively. We interpret this distinct rupture behavior to be the result of the respective slip concentration depths of the two ruptured segments. We analyze geological, seismic, and geodetic evidence and find that the SGT upper crust shows distributed shear deformation and distinct transverse anisotropy, which are associated with folded structures originating from compression of the paleo-Tethys ocean accretional prism realigned by following shear deformation. The SGT receives lateral shear loading from its NS boundary and accommodates a right-step sinistral motion across the terrane boundary faults. The unique tectonic setting of the SGT defines locations and behaviors of internal faulting and strong earthquakes such as the 2021 Maduo earthquake, with the latter occurring on slow-moving faults at intervals of several thousands of years.

Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.

GOAL: The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. BACKGROUND: Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. STUDY: In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. RESULTS: VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). CONCLUSION: VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.

qMrdd2, a novel quantitative resistance locus for maize rough dwarf disease.

BACKGROUND: Maize rough dwarf disease (MRDD), a widespread disease caused by four pathogenic viruses, severely reduces maize yield and grain quality. Resistance against MRDD is a complex trait that controlled by many quantitative trait loci (QTL) and easily influenced by environmental conditions. So far, many studies have reported numbers of resistant QTL, however, only one QTL have been cloned, so it is especially important to map and clone more genes that confer resistance to MRDD. RESULTS: In the study, a major quantitative trait locus (QTL) qMrdd2, which confers resistance to MRDD, was identified and fine mapped. qMrdd2, located on chromosome 2, was consistently identified in a 15-Mb interval between the simple sequence repeat (SSR) markers D184 and D1600 by using a recombinant inbred line (RIL) population derived from a cross between resistant ("80007") and susceptible ("80044") inbred lines. Using a recombinant-derived progeny test strategy, qMrdd2 was delineated to an interval of 577 kb flanked by markers N31 and N42. We further demonstrated that qMrdd2 is an incompletely dominant resistance locus for MRDD that reduced the disease severity index by 20.4%. CONCLUSIONS: A major resistance QTL (qMrdd2) have been identified and successfully refined into 577 kb region. This locus will be valuable for improving maize variety resistance to MRDD via marker-assisted selection (MAS).

Fumarylacetoacetate hydrolase is required for fertility in rice.

MAIN CONCLUSION: The rice OsFAH gene functions identically to that of Arabidopsis SSCD1 encoding FAH. Loss of OsFAH causes rice sterility. Fumarylacetoacetate hydrolase (FAH) is the last enzyme in the tyrosine (Tyr) degradation pathway that is crucial for animals. By genetic analysis of the mutant of Short-day Sensitive Cell Death 1 gene encoding Arabidopsis FAH, we first found the pathway also plays a critical role in plants (Han et al., Plant Physiol 162:1956-1964, 2013). To further understand the role of the Tyr degradation pathway in plants, we investigated a biological function of the rice FAH. Firstly, the cDNA of rice FAH gene (OsFAH) was cloned and confirmed to be able to rescue the Arabidopsis Short-day Sensitive Cell Death 1 mutant defective in the FAH. Then, we identified the OsFAH T-DNA insertion mutant and generated the OsFAH RNA interference lines, and found that loss of OsFAH results in rice sterility. Furthermore, we analyzed expression of the OsFAH gene in roots, stems, leaves and young panicles at booting stage of rice and found that its transcript level was highest in young panicles and lowest in roots. In addition, the expression analysis of ß-glucuronidase driven by OsFAH promoter in transgenic Arabidopsis showed that the OsFAH promoter was highly active in aerial tissues in vegetative stage, and sepals, filaments and stigma in reproductive stage. These results suggested that FAH plays an important role in rice fertility.

Cell death resulted from loss of fumarylacetoacetate hydrolase in Arabidopsis is related to phytohormone jasmonate but not salicylic acid.

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step in Tyr degradation pathway essential to animals but not well understood in plants. Previously, we found that mutation of SSCD1 encoding Arabidopsis FAH causes cell death under short day, which uncovered an important role of Tyr degradation pathway in plants. Since phytohormones salicylic acid (SA) and jasmonate (JA) are involved in programmed cell death, in this study, we investigated whether sscd1 cell death is related to SA and JA, and found that (1) it is accompanied by up-regulation of JA- and SA-inducible genes as well as accumulation of JA but not SA; (2) it is repressed by breakdown of JA signaling but not SA signaling; (3) the up-regulation of reactive oxygen species marker genes in sscd1 is repressed by breakdown of JA signaling; (4) treatment of wild-type Arabidopsis with succinylacetone, an abnormal metabolite caused by loss of FAH, induces expression of JA-inducible genes whereas treatment with JA induces expression of some Tyr degradation genes with dependence of JA signaling. These results demonstrated that cell death resulted from loss of FAH in Arabidopsis is related to JA but not SA, and suggested that JA signaling positively regulates sscd1 cell death by up-regulating Tyr degradation.

GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3ß axis.

Propofol, an intravenous anaesthetic agent, has been found to exhibit antitumour effects in various kinds of cancer cells. However, the potential roles and regulatory mechanisms of propofol in oral squamous cell carcinoma (OSCC) remain unknown. Herein, we found that propofol inhibits OSCC cell growth and promotes cell apoptosis in a dose- and time-dependent manner. Further mechanistic studies revealed that the long noncoding RNA GAS5 is induced by propofol in OSCC cells. Elevated GAS5 acts as a competing endogenous RNA for miR-1297 and attenuates its inhibitory effect on GSK3ß, leading to GSK3ß increase and Mcl1 decrease. Additionally, we found that FoxO1 binds to the promoter of GAS5, facilitating its transcription in response to propofol treatment. Thus, these results suggest that propofol exhibits antitumour effects in OSCC cells and that the FoxO1-GAS5-miR-1297-GSK3ß axis plays an important role in propofol-induced OSCC cell apoptosis.

Loss of fumarylacetoacetate hydrolase causes light-dependent increases in protochlorophyllide and cell death in Arabidopsis.

Fumarylacetoacetate hydrolase (FAH) catalyses the final step of the tyrosine degradation pathway, which is essential to animals but was of unknown importance in plants until we found that mutation of Short-day Sensitive Cell Death1 (SSCD1), encoding Arabidopsis FAH, results in cell death under short-day conditions. The sscd1 mutant accumulates succinylacetone (SUAC), an abnormal metabolite caused by loss of FAH. Succinylacetone is an inhibitor of δ-aminolevulinic acid (ALA) dehydratase (ALAD), which is involved in chlorophyll (Chl) biosynthesis. In this study, we investigated whether sscd1 cell death is mediated by Chl biosynthesis and found that ALAD activity is repressed in sscd1 and that protochlorophyllide (Pchlide), an intermediate of Chl biosynthesis, accumulates at lower levels in etiolated sscd1 seedlings. However, it was interesting that Pchlide in sscd1 might increase after transfer from light to dark and that HEMA1 and CHLH are upregulated in the light-dark transition before Pchlide levels increased. Upon re-illumination after Pchlide levels had increased, reactive oxygen species marker genes, including singlet oxygen-induced genes, are upregulated, and the sscd1 cell death phenotype appears. In addition, Arabidopsis WT seedlings treated with SUAC mimic sscd1 in decline of ALAD activity and accumulation of Pchlide as well as cell death. These results demonstrate that increase in Pchlide causes cell death in sscd1 upon re-illumination and suggest that a decline in the Pchlide pool due to inhibition of ALAD activity by SUAC impairs the repression of ALA synthesis from the light-dark transition by feedback control, resulting in activation of the Chl biosynthesis pathway and accumulation of Pchlide in the dark.

Fumarylacetoacetate hydrolase is involved in salt stress response in Arabidopsis.

MAIN CONCLUSION: Fumarylacetoacetate hydrolase participates in positive regulation of salt stress in Arabidopsis. Fumarylacetoacetate hydrolase (FAH) catalyzes the hydrolysis of fumarylacetoacetate into fumarate and acetoacetate, the final step in the Tyr degradation pathway that is essential to animals. However, the Tyr degradation pathway is not well understood in plants. Previously, we found that mutation of the SHORT-DAY SENSITIVE CELL DEATH 1 (SSCD1) gene encoding FAH in Arabidopsis causes spontaneous cell death under short day, which first indicated that the Tyr degradation pathway also plays an important role in plants. In this study, we found that the SSCD1 gene was up-regulated by salt stress, and the sscd1 mutant was hypersensitive to salt stress. However, the double mutant of SSCD1 and HOMOGENTISATE DIOXYGENASE, in which intermediates of the Tyr degradation pathway could not be produced, displayed a normal response to salt stress. Furthermore, the sscd1 mutant showed more accumulation of reactive oxygen species (ROS) and less up-regulation of some ROS-scavenging genes such as ASCORBATE PEROXIDASE 2 and COPPER/ZINC SUPEROXIDE DISMUTASE 1 compared with wild type under salt stress. In addition, SSCD1 expression was also up-regulated by H2O2, and the sscd1 mutant exhibited hypersensitivity to oxidative stress compared with wild type. Taken together, we concluded that loss of FAH in sscd1 leads to the accumulation of Tyr degradation intermediates, which impairs the up-regulation of some ROS-scavenging genes under salt stress, causing more accumulation of ROS, resulting in the hypersensitivity of sscd1 to salt stress.

GDP-D-mannose epimerase regulates male gametophyte development, plant growth and leaf senescence in Arabidopsis.

Plant GDP-D-mannose epimerase (GME) converts GDP-D-mannose to GDP-L-galactose, a precursor of both L-ascorbate (vitamin C) and cell wall polysaccharides. However, the genetic functions of GME in Arabidopsis are unclear. In this study, we found that mutations in Arabidopsis GME affect pollen germination, pollen tube elongation, and transmission and development of the male gametophyte through analysis of the heterozygous GME/gme plants and the homozygous gme plants. Arabidopsis gme mutants also exhibit severe growth defects and early leaf senescence. Surprisingly, the defects in male gametophyte in the gme plants are not restored by L-ascorbate, boric acid or GDP-L-galactose, though boric acid rescues the growth defects of the mutants, indicating that GME may regulate male gametophyte development independent of L-ascorbate and GDP-L-galactose. These results reveal key roles for Arabidopsis GME in reproductive development, vegetative growth and leaf senescence, and suggest that GME regulates plant growth and controls male gametophyte development in different manners.

Viral effector protein manipulates host hormone signaling to attract insect vectors.

Some plant and animal pathogens can manipulate their hosts to cause them to release odors that are attractive to the pathogens' arthropod vectors. However, the molecular mechanism underlying this process is largely unexplored, and the specific effectors the pathogens employ as well as the pathways within the hosts they target are currently unknown. Here we reveal that the aphid-borne cucumber mosaic virus (CMV) employs its 2b protein, a well-characterized viral suppressor of host RNA interference (VSR), to target the host's jasmonate (JA) hormone pathway, thus acting as a viral inducer of host attractiveness to insect vectors (VIA). 2b inhibits JA signaling by directly interacting with and repressing JA-induced degradation of host jasmonate ZIM-domain proteins, instead of using its VSR activity. Our findings identify a previously defined VSR protein as a VIA and uncover a molecular mechanism CMV uses to manipulate host's attractiveness to insect vectors by targeting host hormone signaling.

Regulation of the WD-repeat/bHLH/MYB complex by gibberellin and jasmonate.

The phytohormones gibberellin (GA) and jasmonate (JA) regulate various aspects of plant development, growth and defense. Previous studies showed that both DELLA repressors in GA pathway and JA-ZIM domain (JAZ) proteins in JA pathway interact with and repress the WD-repeat/bHLH/MYB transcriptional complex to inhibit trichome initiation, and GA and JA respectively induce DELLAs and JAZs degradation to synergistically enhance trichome formation. In this study, we showed that the DELLA protein RGA and JAZ1 competitively bind to ENHANCER OF GLABRA3 (EGL3), a bHLH component of the WD-repeat/bHLH/MYB complex. GA and JA differently affect the expression and protein stability of the components of the WD-repeat/bHLH/MYB complex, and EGL3 and GL3 repress the expression of JAZ genes as a feedback. The novel findings help to understand the mechanism of the WD-repeat/bHLH/MYB complex in GA/JA-regulated trichome formation.

Sugar suppresses cell death caused by disruption of fumarylacetoacetate hydrolase in Arabidopsis.

MAIN CONCLUSION: Sugar negatively regulates cell death resulting from the loss of fumarylacetoacetate hydrolase that catalyzes the last step in the Tyr degradation pathway in Arabidopsis . Fumarylacetoacetate hydrolase (FAH) hydrolyzes fumarylacetoacetate to fumarate and acetoacetate, the final step in the tyrosine (Tyr) degradation pathway that is essential to animals. Previously, we first found that the Tyr degradation pathway plays an important role in plants. Mutation of the SSCD1 gene encoding FAH in Arabidopsis leads to spontaneous cell death under short-day conditions. In this study, we presented that the lethal phenotype of the short-day sensitive cell death1 (sscd1) seedlings was suppressed by sugars including sucrose, glucose, fructose, and maltose in a dose-dependent manner. Real-time quantitative PCR (RT-qPCR) analysis showed the expression of Tyr degradation pathway genes homogentisate dioxygenase and maleylacetoacetate isomerase, and sucrose-processing genes cell-wall invertase 1 and alkaline/neutral invertase G, was up-regulated in the sscd1 mutant, however, this up-regulation could be repressed by sugar. In addition, a high concentration of sugar attenuated cell death of Arabidopsis wild-type seedlings caused by treatment with exogenous succinylacetone, an abnormal metabolite resulting from the loss of FAH in the Tyr degradation pathway. These results indicated that (1) sugar could suppress cell death in sscd1, which might be because sugar supply enhances the resistance of Arabidopsis seedlings to toxic effects of succinylacetone and reduces the accumulation of Tyr degradation intermediates, resulting in suppression of cell death; and (2) sucrose-processing genes cell-wall invertase 1 and alkaline/neutral invertase G might be involved in the cell death in sscd1. Our work provides insights into the relationship between sugar and sscd1-mediated cell death, and contributes to elucidation of the regulation of cell death resulting from the loss of FAH in plants.

A GC/MS method for determination of succinylacetone in Arabidopsis thaliana.

Succinylacetone was known to be a toxic metabolite of tyrosine in human and animals caused by blockage of the final step in tyrosine degradation pathway, but its existence in plant was unclear though the metabolic disturbance of tyrosine was also found in plant. A GC-MS method for determination of succinylacetone in Arabidopsis thaliana was developed for the first time. Both oximation and silylation were applied in the derivation procedure, and a low-temperature condition before completion of oximation was found to be necessary to obtain good linearity of the calibration curve due to the thermolability of succinylacetone. The specific chromatogram pattern formed by the four isomers of succinylacetone derivatives provided a helpful feature for its identification. The detection limit of the proposed method was 0.25 ppm in A. thaliana. The recoveries were between 95.4 and 109.3 % with the coefficient of variation ranging from 4.36 to 7.81 % for intra-day assays and 6.47 to 8.52 % for inter-day assays. Application to wild-type and the short-day sensitive cell death 1 mutant of A. thaliana represented an obvious correlation between the measured amount of succinylacetone and wilting symptom, suggesting the proposed method could be a powerful tool in further study on toxicology of succinylacetone and tyrosine catabolism in plants.

Oridonin upregulates PTEN through activating p38 MAPK and inhibits proliferation in human colon cancer cells.

Oridonin (ORI) has been reported as an antiproliferation and apoptosis-inducing natural product in various cancer cells. However, the exact molecular mechanism underlying these effects remains unclear. In the present study, we demonstrated the antiproliferation effect of ORI in HCT116 cells, and analyzed the possible molecular mechanism which mediates this effect. We found that ORI inhibits proliferation, induces cell cycle arrest and apoptosis in HCT116 cells, thus also tumor growth. Mechanically, we found that ORI has no substantial effect on mRNA expression of phosphatase and tensin homologue (PTEN), but increases the total protein level of PTEN and markedly reduces the phosphorylation of PTEN; Exogenous expression of PTEN potentiates the anticancer effect of ORI, while knockdown of PTEN attenuates it. ORI also increases the phosphorylation of p38 MAPK, and p38 MAPK-specific inhibitor reduces the antiproliferation effect ORI in HCT116 cells. Moreover, inhibition of p38 MAPK increases the phosphorylation of PTEN, and reverses ORI-induced decrease of PTEN phosphorylation. Our findings suggested that ORI may be a potential anticancer drug for colon cancer, this effect may be mediated by enhancing the function of PTEN through reducing its phosphorylation, which may be resulted from the ORI-induced activation of p38 MAPK.