Oleuropein mitigates non-alcoholic fatty liver disease (NAFLD) and modulates liver metabolites in high-fat diet-induced obese mice via activating PPARα.

BACKGROUND: This study aimed to elucidate the mechanism of oleuropein (OLE) ameliorates non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms. RESULTS: Male C57BL/6J mice were fed either a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.03% (w/w) OLE for 16 weeks. OLE supplementation decreased body weight and liver weight, improved serum lipid profiles, and ameliorated HFD-induced hepatic dysfunction. Liver metabolomics analysis revealed that OLE increased the levels of nicotinamide, tauroursodeoxycholic acid, taurine, and docosahexaenoic acid, which were beneficial for lipid homeostasis and inflammation regulation. OLE exerted its protective effects by activating peroxisome proliferator-activated receptor alpha (PPARα), a key transcription factor that regulates fibroblast growth factor 21 (FGF21) expression and modulates lipid oxidation, lipogenesis and inflammation pathways. Importantly, OLE supplementation did not significantly affect body weight or liver weight in PPARα knockout (PPARα KO) mice, indicating that PPARα is essential for OLE-mediated NAFLD prevention. CONCLUSION: Our results suggest that OLE alleviates NAFLD in mice by activating PPARα and modulating liver metabolites. © 2024 Society of Chemical Industry.

Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China.

BACKGROUND: This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant. METHODS: A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8-10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis. RESULTS: The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS. CONCLUSIONS: Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.

Facial skin characteristics and concerns in Indonesia: A cross-sectional observational study.

BACKGROUND: Facial skin characteristics and appearance vary according to ethnicity. While much of this knowledge is derived from the Caucasian population, lately there have been efforts to gain such understanding in various regions in Asia.  In this paper, we have built an understanding of such features in Indonesia. In Indonesia, a section of females wears a traditional veil (hijab) to cover the scalp and part of face. The influence of the hijab on facial skin attributes was also investigated. METHODS: In a cross-sectional observational study design involving 419 female volunteers in Jakarta, Indonesia, facial skin attributes (colour, radiance, hydration, trans-epidermal water loss [TEWL], wrinkles, fine lines, pores, and sebum levels) and conditions (melasma, post-inflammatory hyperpigmentation (PIH), solar lentigines/ senile lentigines, seborrheic keratoses and acne) were assessed by trained operators and dermatologists using standard validated instruments and scales. RESULTS: With age, facial skin colour showed darkening in cheek; forehead on the other hand showed slight lightening. The skin evenness and radiance decreased, substantially. Aging attributes measured in terms of lines, wrinkles, and under-eye dark circles showed deterioration with age; the decline was progressively faster than colour change. Facial image data analysis corroborated these findings. Skin hydration remained similar across the age groups even though the skin barrier function measured in terms of TEWL improved with age. Sebum levels in the skin were similar up to the age of 50 but declined in the next group of 50-60 year. Pore severity increased with age. Melasma, seborrheic keratosis and PIH showed a high prevalence (>∼50%) at the young age group (20-30 years), itself. Melasma prevalence attained 100% in the age group of 41-50 year and onwards, and its severity similarly showed a steady rise with age. PIH on the other hand showed a steady decline with age. Solar lentigines prevalence (∼30%) did not change much across age groups, and the severity scores were similar in age groups up to 50 year but increased substantially in 51-60-year age groups. Seborrheic keratosis was similar (∼47%) in age groups up 20-40 year but steadily increased in upper age groups. Its severity was similar in the age groups of 20-30 year and 31-40 year but showed a two-fold increase in subsequent age groups. Acne was 10% in the age group of 20-30 year and declined gradually to 0.7% in the 51-60-year age group. Hijab wearers showed slight protection in skin colour darkening and improvement of evenness and radiance but were similar on aging (fine lines and wrinkles on crow's feet, under eye and peri-oral areas) markers to non-wearers. In general, in majority of age-groups, hijab wearers showed a higher prevalence of melasma, solar/senile lentigines, seborrheic keratosis and PIH.

Acute aortic dissection with right-sided chest and back pain accompanied by left-sided limb dyskinesia.

We retrospectively studied the diagnosis and treatment of a case of AAD misdiagnosed as stroke since atypical symptoms as the first manifestation, and discussed the clinical features and manifestations, diagnosis, and differential diagnosis of the case in the context of relevant domestic and international literature. The patient, a 49­year-old male with herpes zoster for more than 1 month, presented with sudden onset of right-sided chest and back pain, accompanied by numbness and weakness of the left limb, and was tentatively diagnosed with post-herpetic neuralgia combined with stroke due to the history of herpes zoster. Non-specific ST-T alterations, D-dimer 20ug / ml, and non-traumatic angiographic findings in the transthoracic and abdominal aorta demonstrated slight thickening of the patient's ascending aorta, and the lumen of the root sinus region showed intimal flap formation with a larger pseudocoel and smaller true lumen, which ultimately confirmed the diagnosis of acute aortic coarctation with atypical presentation. So clinicians need to improve their basic theoretical knowledge, strengthen the understanding of AAD, focus on physical examination, improve relevant auxiliary examinations expeditiously, and pay attention to the significance of specific auxiliary examinations in order to decrease misdiagnosis and missed diagnosis of atypical manifestations of AAD patients.

[Research progress of Curcuma kwangsiensis root tubers and analysis of liver protection and anti-tumor mechanisms based on Q-markers].

Curcuma kwangsiensis root tuber is a widely used genuine medicinal material in Guangxi, with the main active components of terpenoids and curcumins. It has the effects of promoting blood circulation to relieve pain, moving Qi to relieve depression, clearing heart and cooling blood, promoting gallbladder function and anti-icterus. Modern research has proved its functions in liver protection, anti-tumor, anti-oxidation, blood lipid reduction and immunosuppression. Considering the research progress of C. kwangsiensis root tubers and the core concept of quality marker(Q-marker), we predicted the Q-markers of C. kwangsiensis root tubers from plant phylogeny, chemical component specificity, traditional pharmacodynamic properties, new pharmacodynamic uses, chemical component measurability, processing methods, compatibility, and components migrating to blood. Curcumin, curcumol, curcumadiol, curcumenol, curdione, germacrone, and ß-elemene may be the possible Q-markers. Based on the predicted Q-markers, the mechanisms of the liver-protecting and anti-tumor activities of C. kwangsiensis root tubers were analyzed. AKT1, IL6, EGFR, and STAT3 were identified as the key targets, and neuroactive ligand-receptor interaction signaling pathway, nitrogen metabolism pathway, cancer pathway, and hepatitis B pathway were the major involved pathways. This review provides a basis for the quality evaluation and product development of C. kwangsiensis root tubers and gives insights into the research on Chinese medicinal materials.

Cardiotoxicity induced by Cochinchina momordica seed extract in zebrafish.

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti-ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE-induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose-dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

GSA-Human: Genome Sequence Archive for Human.

The Genome Sequence Archive for Human (GSA-Human) is a data repository specialized for human genetic related data derived from biomedical researches, and also supports the data collection and management of National Key Research and Development Projects. GSA-Human has a data security management strategy according to the national regulations of human genetic resources. It provides two different models of data access: Open-access and Controlled-access. Open-access data are universally and freely accessible for global researchers, while Controlled-access ensures that data are accessed only by authorized users with the permission of the Data Access Committee (DAC). Till July 2021, GSA-Human has housed more than 5.27 PB of data from 750 datasets.

[Traditional medicinal plants for arthropod-borne diseases of five countries in Lancang-Mekong region:a review].

Arthropod-borne diseases, such as malaria and dengue fever, have frequently beset five countries(Cambodia, Vietnam, Laos, Myanmar, and Thailand) in the tropical rainy Lancang-Mekong region, which pose a huge threat to social production and daily life. As a resort to such diseases, chemical drugs risk the resistance in plasmodium, non-availability for dengue virus, and pollution to the environment. Traditional medicinal plants have the multi-component, multi-target, and multi-pathway characteristics, which are of great potential in drug development. Exploring potential medicinals for arthropod-borne diseases from traditional medicinal plants has become a hot spot. This study summarized the epidemiological background of arthropod-borne diseases in the Lancang-Mekong region and screened effective herbs from the 350 medicinal plants recorded in CHINA-ASEAN Traditional Medicine. Based on CNKI, VIP, and PubMed, the plants for malaria and dengue fever and those for killing and repelling mosquitoes were respectively sorted out. Their pharmacological effects and mechanisms were reviewed and the material basis was analyzed. The result is expected to serve as a reference for efficient utilization of medicinal resources, development of effective and safe drugs for malaria and dengue fever, and the further cooperation between China and the other five countries in the Lancang-Mekong region.

D-Galactose-induced oxidative stress and mitochondrial dysfunction in the cochlear basilar membrane: an in vitro aging model.

The cochlear basilar membrane (CBM) contains inner hair cells and outer hair cells that convert sound waves into electrical signals and transmit them to the central auditory system. Cochlear aging, the primary reason of age-related hearing loss, can reduce the signal transmission capacity. There is no ideal in vitro aging model of the CBM. In this study, we cultured the CBM, which was dissected from the cochlea of the C57BL/6 mice 5 days after birth, in a medium containing 20 mg/mL, 40 mg/mL, or 60 mg/mL D-galactose (D-gal). Compared with the control group, the levels of senescence-associated ß-galactosidase were increased in a concentration-dependent manner in the CBM of the D-gal groups. In addition, levels of the mitochondrial superoxide and patterns of an age-related mitochondrial DNA3860-bp deletion were significantly increased. The ATP levels and the membrane potential of the mitochondrial were significantly decreased in the CBM of the D-gal groups compared with the control group. Furthermore, in comparison with the control group, damaged hair cell stereocilia and a loss of inner hair cell ribbon synapses were observed in the CBM of the D-gal groups. A loss of hair cells and activation of caspase-3-mediated outer hair cell apoptosis were also observed in the CBM of the high-dose D-gal group. These insults induced by D-gal in the CBM in vitro were similar to the ones that occur in cochlear natural aging in vivo. Thus, we believe that this is a successful in vitro aging model using cultured CBM. These results demonstrate the effects of mitochondrial oxidative damage on presbycusis and provide a reliable aging model to study the mechanisms of presbycusis in vitro.

Location affects fatty acid composition in Camellia sinensis cv Tieguanyin fresh leaves.

Tieguanyin tea is a typical representative of oolong tea in China, and is famous for its orchid-like aroma. Fatty acids are one of the important precursors for aroma production. However, fatty acid contents and compositions in Tieguanyin largely remain undefined. In this study, we quantified the fatty acid composition in Tieguanyin and its offspring by gas chromatography-flame ionization detector, and compared the effects of growth sites and harvest time on the leaf fatty acid composition. The results showed that total fatty acid contents in Tieguanyin fresh leaves were higher than its offspring. Growth sites had significant impacts on fatty acid contents. Tieguanyin grown in Anxi County showed higher total fatty acid contents, and higher ratio of total unsaturated fatty acids to total saturated fatty acids. The fresh leaves in the morning showed higher total fatty acid contents compared to samples harvested in the afternoon or evening, suggesting a dynamic fatty acid degradation during day period. During tea processing, unsaturated fatty acids including linolenic acid, linoleic acid and oleic acid (18:1Δ9c) decreased 13.1%, 13.2% and 84.2%, respectively. The ratio of unsaturated fatty acids to saturated fatty acids still was above 300%. We found that Tieguanyin was a typical 18:3 plant, and the higher ratio of unsaturated fatty acids to saturated fatty acids of Tieguanyin grown in Anxi County may contribute to its characteristics aroma.

Air-stable n-doped black phosphorus transistor by thermal deposition of metal adatoms.

In this work, a simple and effective thermal deposition method is described to enhance the stability and achieve n-doping of two-dimensional black phosphorus (BP), resulting in the successful fabrication of logic devices. By doping with Al adatoms, the stability of BP against oxidation is enhanced and the transfer characteristics are maintained for several days under ambient conditions. Furthermore, the resulting BP is n-doping showing a negative-shifted threshold voltage and enhanced electron mobility. The mechanism of Al-doping is investigated by first-principles calculation and Al induces a downward shift of the conduction band minimum and increases the Fermi level. In addition, integration of bare BP and Al-doped BP enables the fabrication of various logic devices such as inverters and p-n diodes. This work reveals a facile strategy to simultaneously enhance the stability and regulate the conductivity of BP by doping with metal adatoms boding well for device applications.

NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats.

Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.

Mitochondrial DNA 3,860-bp Deletion Increases with Aging in the Auditory Nervous System of C57BL/6J Mice.

BACKGROUND/AIMS: Mitochondrial DNA (mtDNA) is sensitive to oxidative damage during aging, which can result in mtDNA mutations. A previous study reported that a 3,860-bp mtDNA deletion, similar to a 4,977-bp mtDNA deletion in humans, is also common occurrence in murine tissues, and increases in the brain and liver with aging. However, no previous study evaluated both topics in the murine auditory nervous system. METHODS: We compared mtDNA oxidative damage, mitochondrial ultrastructural changes, and the frequency of the 3,860-bp deletion in the peripheral (spiral ganglion, SG) and central (auditory cortex, AC) auditory nervous system of C57BL/6J mice aged 2, 12, and 18 months. RESULTS: We found that the threshold of auditory brainstem response increased with age along with the signal of 8-hydroxy-2'-deoxyguanosine - a marker of DNA oxidative damage - in the mitochondria of SG and AC neurons. The mitochondrial ultrastructural damage also increased with aging in the SG and AC neurons. Moreover, the relative amount of mtDNA 3,860-bp deletion in 12- and 18-month-old mice was significantly higher in the SG and AC as compared to 2-month-old mice. CONCLUSION: These results suggest that the mtDNA 3,860-bp deletion is common in the auditory nervous system of mice and increases with age and may contribute to age-related hearing loss.

Improved Drought Monitoring Index Using GNSS-Derived Precipitable Water Vapor over the Loess Plateau Area.

Standardized precipitation evapotranspiration index (SPEI) is an acknowledged drought monitoring index, and the evapotranspiration (ET) used to calculated SPEI is obtained based on the Thornthwaite (TH) model. However, the SPEI calculated based on the TH model is overestimated globally, whereas the more accurate ET derived from the Penman-Monteith (PM) model recommended by the Food and Agriculture Organization of the United Nations is unavailable due to the lack of a large amount of meteorological data at most places. Therefore, how to improve the accuracy of ET calculated by the TH model becomes the focus of this study. Here, a revised TH (RTH) model is proposed using the temperature (T) and precipitable water vapor (PWV) data. The T and PWV data are derived from the reanalysis data and the global navigation satellite system (GNSS) observation, respectively. The initial value of ET for the RTH model is calculated based on the TH model, and the time series of ET residual between the TH and PM models is then obtained. Analyzed results reveal that ET residual is highly correlated with PWV and T, and the correlate coefficient between PWV and ET is -0.66, while that between T and ET for cases of T larger or less than 0 °C are -0.54 and 0.59, respectively. Therefore, a linear model between ET residual and PWV/T is established, and the ET value of the RTH model can be obtained by combining the TH-derived ET and estimated ET residual. Finally, the SPEI calculated based on the RTH model can be obtained and compared with that derived using PM and TH models. Result in the Loess Plateau (LP) region reveals the good performance of the RTH-based SPEI when compared with the TH-based SPEI over the period of 1979-2016. A case analysis in April 2013 over the LP region also indicates the superiority of the RTH-based SPEI at 88 meteorological and 31 GNSS stations when the PM-based SPEI is considered as the reference.

SH3BP1-induced Rac-Wave2 pathway activation regulates cervical cancer cell migration, invasion, and chemoresistance to cisplatin.

Cervical cancer still remains the fourth most common cancer, affecting women worldwide with large geographic variations in cervical cancer incidence and mortality rates. SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target Wave2 is required for cell motility, thus regarded as an essential regulator of cancer cell metastasis. However, the exact effects and molecular mechanisms of SH3BP1 in cervical cancer progression are still unknown. The present study is aimed to investigate the mechanism of SH3BP1 in regulation of cervical cancer cell metastasis and chemoresistance. In the present study, we demonstrated a high SH3BP1 expression in cervical cancer tissues; a higher SH3BP1 expression is also correlated with a shorter overall survival of patients with cervical cancer. Further, we revealed that SH3BP1 overexpression promoted the invasion, migration, and chemoresistance of cervical cancer cell through increasing Rac1 activity and Wave2 protein level. The promotive effect of SH3BP1 could be partially reversed by a Rac1 inhibitor, NSC 23766. In cisplatin-resistant cervical cancer tissues, SH3BP1, Rac1, and Wave2 mRNA expression was significantly up-regulated compared to that of the cisplatin-sensitive cervical cancer tissues. Taken together, SH3BP1/Rac1/Wave2 pathway may potentially act as an effective therapeutic target combined with traditional cisplatin-based chemotherapy for cervical cancer.

Activating nuclear xenobiotic receptors and triggering ER stress and hepatic cytochromes P450 systems in quails (Coturnix C. coturnix) during atrazine exposure.

Atrazine (ATR) is one of the most widely detected contaminant in the ecosystem. Nuclear xenobiotic receptors are activated by herbicides and induce the transcription of CYP450 isoforms involved in xenobiotic metabolism and transport. However, little is known about hepatic nuclear xenobiotic receptors in birds are responsible for ATR-induced hepatotoxicity via regulating the cytochrome P450 enzyme systems (CYP450s). The objective of this study was to investigate the mechanism of ATR hepatotoxicity in quails. For this purpose, male quails were dosed by oral gavage from sexual immaturity to maturity with 0, 50, 250, and 500 mg/kg/day ATR for 45 days. The results showed that ATR exposure caused the hepatotoxicity damage and endoplasmic reticulum (ER) degeneration. It suggested that ER is a target organelle of ATR toxicity in hepatocytes. ATR exposure disrupted the hepatic CYP450s homeostasis. This study also demonstrated that ATR triggered the CYP450 isoforms transcription via activating the hepatic CAR/PXR pathway. The present study provides new insights regarding the mechanism of the ATR-induced hepatotoxicity through activating nuclear xenobiotic receptors and triggering ER stress and hepatic CYP450s in quails.

Modelling of XCO2 Surfaces Based on Flight Tests of TanSat Instruments.

The TanSat carbon satellite is to be launched at the end of 2016. In order to verify the performance of its instruments, a flight test of TanSat instruments was conducted in Jilin Province in September, 2015. The flight test area covered a total area of about 11,000 km² and the underlying surface cover included several lakes, forest land, grassland, wetland, farmland, a thermal power plant and numerous cities and villages. We modeled the column-average dry-air mole fraction of atmospheric carbon dioxide (XCO2) surface based on flight test data which measured the near- and short-wave infrared (NIR) reflected solar radiation in the absorption bands at around 760 and 1610 nm. However, it is difficult to directly analyze the spatial distribution of XCO2 in the flight area using the limited flight test data and the approximate surface of XCO2, which was obtained by regression modeling, which is not very accurate either. We therefore used the high accuracy surface modeling (HASM) platform to fill the gaps where there is no information on XCO2 in the flight test area, which takes the approximate surface of XCO2 as its driving field and the XCO2 observations retrieved from the flight test as its optimum control constraints. High accuracy surfaces of XCO2 were constructed with HASM based on the flight's observations. The results showed that the mean XCO2 in the flight test area is about 400 ppm and that XCO2 over urban areas is much higher than in other places. Compared with OCO-2's XCO2, the mean difference is 0.7 ppm and the standard deviation is 0.95 ppm. Therefore, the modelling of the XCO2 surface based on the flight test of the TanSat instruments fell within an expected and acceptable range.

Comparative transcriptome profiling of a rice line carrying Xa39 and its parents triggered by Xanthomonas oryzae pv. oryzae provides novel insights into the broad-spectrum hypersensitive response.

BACKGROUND: Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a devastating rice disease worldwide. Xa39 is a resistance (R) gene with a broad-spectrum hypersensitive response (BSHR) to Xoo. Nevertheless, the molecular mechanisms of resistance mediated by Xa39 remain unclear. In this study, the transcriptome profiling of a rice line carrying Xa39 and its parents at the early stage of Xoo infection were investigated. RESULTS: A rice introgression line H471 carrying Xa39 exhibited a typical local hypersensitive response phenotype, accompanied by programmed cell death after inoculation with the Xoo Philippines' race 9b. Transcriptome profiling of H471 and its parents at 1 and 2 days post-inoculation was performed using RNA sequencing. In total, 306 differentially expressed genes (DEGs) were identified in H471 compared with its recurrent parent Huang-Hua-Zhan after inoculation with Xoo. Among them, 121 (39.5%) genes, with functional enrichments that were related to defense response, protein amino acid phosphorylation, and apoptosis, were found to be constitutively expressed. The other 185 (60.5%) genes, with GO terms that belonged to defense response, were significantly responsive to Xoo infection in H471. Ten up-regulated and 12 down-regulated genes encoding intracellular immune receptors were identified in H471 compared with Huang-Hua-Zhan. LOC_Os11g37759, which was located in the fine-mapping region harboring Xa39, is a Xa39 candidate gene. The putative BSHR-related co-regulatory networks were constructed using 33 DEGs from four functional groups, including gibberellic acid receptors and brassinosteroid regulators, which were differentially co-expressed with LOC_Os11g37759 in infected H471. Our results indicated that there might be cross-talk between the Xa39-mediated signal transduction cascades and the GA/BR signaling pathway, and that the defense mechanism was related to diverse kinases, transcription factors, post-translational regulation, and R genes. CONCLUSIONS: The present study provides the comprehensive transcriptome profile of a rice introgression line carrying Xa39 and its parents, and identifies a set of DEGs involved in BSHR mediated by Xa39. These data provide novel insights into the regulatory networks of plant disease resistance mediated by R genes, and the identified DEGs will serve as candidates for Xa39 cloning and for further understanding the molecular mechanism of BSHR.

Four New Cyclohexylideneacetonitrile Derivatives from the Hypocotyl of Mangrove (Bruguiera gymnorrhiza).

Four new cyclohexylideneacetonitrile derivatives 1-4, named menisdaurins B-E, as well as three known cyclohexylideneacetonitrile derivatives--menisdaurin (5), coclauril (6), and menisdaurilide (7)--were isolated from the hypocotyl of a mangrove (Bruguiera gymnorrhiza). The structures of the isolates were elucidated on the basis of extensive spectroscopic analysis. Compounds 1-7 showed anti-Hepatitis B virus (HBV) activities, with EC50 values ranging from 5.1 ± 0.2 µg/mL to 87.7 ± 5.8 µg/mL.

Risk factors associated with early and late recurrence after curative resection of hepatocellular carcinoma: a single institution's experience with 398 consecutive patients.

BACKGROUND: Surgical resection is an important curative treatment for hepatocellular carcinoma (HCC); however, some patients experience an unexpected recurrence even after hepatectomy. The present study aimed to investigate risk factors and predictive criteria for early and late recurrence of HCC after resection. METHODS: A retrospective analysis of 398 Chinese patients who received curative resection for HCC was conducted. Patients were divided into three groups: without recurrence, early recurrence, and late recurrence. Prognostic factors and predictive criteria for early and late recurrence were statistically analyzed. RESULTS: The cumulative recurrence-free survival rates at 1, 2, 3, 4, and 5 years were 75.5%, 58.2%, 54.1%, 40.5%, and 28.7%, respectively. The distribution of the time to recurrence suggested that recurrence could be divided into early phase (before 2 years; n=164) and late phase (after 2 years; n=83). Cox's multivariate proportional hazard model analysis revealed that multiplicity of tumors (P=0.004) and venous infiltration (P=0.002) were independent risk factors associated with early recurrence. In contrast, indocyanine green retention rate at 15 minutes (P=0.007), serum albumin level (P=0.045), and HBeAg status (P=0.028) proved to be significant independent adverse prognostic factors for late recurrence. Patients with at least 1 of the 2 early recurrence risk factors (multiplicity of tumors ≥ 2 and venous infiltration) or with 2 or more late recurrence risk factors are often susceptible to recurrence (P=1.36e-4 and 1.0e-6, respectively). CONCLUSIONS: Early and late recurrences correlate with different risk factors and predictive criteria. Early recurrence primarily results from intrahepatic metastases, while late recurrence may be multicentric in origin.