Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration.

BACKGROUND: Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. METHODS: At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. RESULTS: This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. CONCLUSION: This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

Aberrant DNA Methylation Profile of Dickkopf-1 in Ankylosing Spondylitis.

In recent years, the impact of methylation modifications on Dickkopf-1 (DKK1) in relation to ankylosing spondylitis (AS) has remained elusive. Our objective was to investigate the potential link between DKK1 methylation patterns and transcript levels and AS susceptibility. DNA methylation level of DKK1 was measured in 82 AS and 82 healthy controls (HCs) using targeted bisulfite sequencing. In addition, the transcript level of DKK1 in peripheral blood mononuclear cells from 35 AS patients and 35 HCs was detected using real-time quantitative transcription-polymerase chain reaction. Our study showed that the DKK1 was significantly hypomethylated in AS patients (P < 0.001). The Receiver operating characteristic curve (ROC) showed that DKK1 methylation may be a potential biomarker. The results showed that the difference in DKK1 transcript levels between AS and HCs was not statistically significant. Further analysis showed that DKK1 methylation levels were positively correlated with age and negatively correlated with C-reactive protein levels, neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). The methylation level of DKK1 in PBMC of AS patients was significantly lower than that of HCs, and DKK1 methylation may be associated with susceptibility to AS. In addition, DNA methylation levels of DKK1 were negatively correlated with the level of inflammation in AS patients.

Multi-omics analysis reveals changes in tryptophan and cholesterol metabolism before and after sexual maturation in captive macaques.

Rhesus macaques (Macaca mulatta, RMs) are widely used in sexual maturation studies due to their high genetic and physiological similarity to humans. However, judging sexual maturity in captive RMs based on blood physiological indicators, female menstruation, and male ejaculation behavior can be inaccurate. Here, we explored changes in RMs before and after sexual maturation based on multi-omics analysis and identified markers for determining sexual maturity. We found that differentially expressed microbiota, metabolites, and genes before and after sexual maturation showed many potential correlations. Specifically, genes involved in spermatogenesis (TSSK2, HSP90AA1, SOX5, SPAG16, and SPATC1) were up-regulated in male macaques, and significant changes in gene (CD36), metabolites (cholesterol, 7-ketolithocholic acid, and 12-ketolithocholic acid), and microbiota (Lactobacillus) related to cholesterol metabolism were also found, suggesting the sexually mature males have stronger sperm fertility and cholesterol metabolism compared to sexually immature males. In female macaques, most differences before and after sexual maturity were related to tryptophan metabolism, including changes in IDO1, IDO2, IFNGR2, IL1Β, IL10, L-tryptophan, kynurenic acid (KA), indole-3-acetic acid (IAA), indoleacetaldehyde, and Bifidobacteria, indicating that sexually mature females exhibit stronger neuromodulation and intestinal immunity than sexually immature females. Cholesterol metabolism-related changes (CD36, 7-ketolithocholic acid, 12-ketolithocholic acid) were also observed in female and male macaques. Exploring differences before and after sexual maturation through multi-omics, we identified potential biomarkers of sexual maturity in RMs, including Lactobacillus (for males) and Bifidobacterium (for females) valuable for RM breeding and sexual maturation research.

Induction of Sestrin2 by pterostilbene suppresses ethanol-triggered hepatocyte senescence by degrading CCN1 via p62-dependent selective autophagy.

Hepatocyte senescence is a key event participating in the progression of alcoholic liver disease. Autophagy is a critical biological process that controls cell fates by affecting cell behaviors like senescence. Pterostilbene is a natural compound with hepatoprotective potential; however, its implication for alcoholic liver disease was not understood. This study was aimed to investigate the therapeutic effect of pterostilbene on alcoholic liver disease and elucidate the potential mechanism. Our results showed that pterostilbene alleviated ethanol-triggered hepatocyte damage and senescence. Intriguingly, pterostilbene decreased the protein abundance of cellular communication network factor 1 (CCN1) in ethanol-exposed hepatocytes, which was essential for pterostilbene to execute its anti-senescent function. In vivo studies verified the anti-senescent effect of pterostilbene on hepatocytes of alcohol-intoxicated mice. Pterostilbene also relieved senescence-associated secretory phenotype (SASP), redox imbalance, and steatosis by suppressing hepatic CCN1 expression. Mechanistically, pterostilbene-forced CCN1 reduction was dependent on posttranscriptional regulation via autophagy machinery but not transcriptional regulation. To be specific, pterostilbene restored autophagic flux in damaged hepatocytes and activated p62-mediated selective autophagy to recognize and lead CCN1 to autolysosomes for degradation. The protein abundance of Sestrin2 (SESN2), a core upstream modulator of autophagy pathway, was decreased in ethanol-administrated hepatocytes but rescued by co-treatment with pterostilbene. Induction of SESN2 protein by pterostilbene rescued ethanol-triggered autophagic dysfunction in hepatocytes, which then reduced senescence-associated markers, postponed hepatocyte senescence, and relieved alcohol-caused liver injury and inflammation. In conclusion, this work discovered a novel compound pterostilbene with therapeutic implications for alcoholic liver disease and uncover its underlying mechanism.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Research on the relationship between common metabolic syndrome and meteorological factors in Wuhu, a subtropical humid city of China.

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis's result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients.

Levels, distributions and influential factors of residential airborne culturable bacteria in 12 Chinese cities: Multicenter on-site survey among dwellings.

Residential airborne culturable bacteria (RAB) are commonly used to assess indoor microbial loads, which is a very effective and recognized indicator of public concern about residential air quality. Many countries and organizations have set exposure limits for residential bacteria. Nevertheless, few studies have been conducted in multicenter cities about the distribution and influencing factors of RAB. It is a challenge to investigate the distribution of RAB and identify the association between indoor influencing variables and RAB in China. The current finding implied the comparative results from a one-year on-site survey of 12 cities in China. The concentration of RAB ranged from 0 CFU/m3 to 18,078 CFU/m3, with an arithmetic median of 350 CFU/m3. RAB concentrations were more in the warm season than those in the cold season, and were more in the bedrooms than those in the living rooms. Indoor environmental indicators (including PM2.5 and PM10) showed the mediating role in the process of temperature and relative humidity effects on RAB. . Influential factors including family-related information (income), architectural characteristics (house type, building history, living floor, the layers of window glass, and decoration) and lifestyle behaviors (heating, new furniture, incense-burned, insecticides-used, air condition-used, and plants-growed) were related with the concentration of RAB. This study presents essential data on the distribution of RAB in some Chinese cities, and reveals the residential influential factors that might minimize health risk from RAB.

The relationship of residential formaldehyde pollution in 11 Chinese cities to schoolchildren pneumonia prevalence in actual living condition.

Residential formaldehyde pollution is one of the leading residential harmful pollutants with a large production and consumption globally and remains much uncertainty in Chinese families with huge health burden for children worldwide. A multi-center observation study from 11 cities was conducted to investigate residential formaldehyde pollution levels measured by phenol reagent spectrophotometry. Data on household characteristics and schoolchildren's health were collected by questionnaire. The median concentration of residential formaldehyde was 0.025 (0.002-0.281) mg/m3 among 11 cities with the total exceeding standard rate of 7.40% according to the reference value of 0.10 mg/m3 (1-h average). Residential formaldehyde pollution in warm season, bedrooms and northern cities was more serious than that in cold season, living rooms and southern cities, respectively. The potential influencing factors of residential formaldehyde included household characteristics (distance from a traffic road, building history, residence duration, window glass layers, decoration and furniture) and use of air conditioner. The positive regulation effect of temperature on residential formaldehyde was explored with the approximately turning-point temperature of 28.9 °C for peak concentration. Long-term exposure to residential formaldehyde of low concentrations (0.010-0.090 mg/m3) would increase the prevalence of childhood pneumonia and a more stringent criteria value for residential formaldehyde should be discussed cautiously.

Association of indoor noise level with depression in hotel workers: A multicenter study from 111 China's cities.

Several studies have elucidated the link between outdoor noise and depression, but the relationship between indoor noise levels and depression symptoms in residential and public places remains unclear. This study was a multicenter observational study with a cross-sectional design. In 2019, a total of 10 545 indoor noise levels on-site and 26 018 health data from practitioners were collected from 2402 hotels in 111 cities. Indoor daily noise data levels were detected, and PHQ-9 questionnaires were used to collect health data. Logistic analysis was used to determine the association between depression score and noise level, negative binomial regression was used to determine potential risks. The geometric mean indoor noise level was 38.9 dB (A), with approximately 40.9% of hotels exceeding the 45 dB value (A). Approximately 19.1% of hotel workers exhibited mild and above depressive symptoms. In addition to functional zoning, geographic location, central air conditioner, decoration status, and other factors had an impact on noise levels (p < 0.05). Results of logistic and negative binomial regression showed the following: (1) there was significantly positive association between indoor noise and high depression scores above 2 (OR = 1.007, 95% CI: 1.002, 1.012) and (2) some sub-groups were more susceptible to this effect, especially for the younger female workers working in the first-tier cities, having higher education level, lower level of income, smoking, and longer working hours. This study confirms an early potential effect of indoor noise on depression. It is recommended to implement evidence-based measures to control noise sources in hotels.

Characteristics, distribution, and children exposure assessment of 13 metals in household dust in China: A big data pilot study.

To explore the pollution characteristics of metals in household dust in China and their exposure to children, this study searched peer-reviewed papers published during 1980-2020 and analyzed 30 eligible papers screened under the per-decided strategy. We evaluated the sample-weighted concentration (SWC) of each metal, explored the sources of metals, and presented the quantitative description of spatial-temporary characteristics and children exposure to 13 metals with multi-route under a general living scenario. The results showed the concentrations of 13 metals with a range of 0.89-29 090.19 mg/kg. The SWC of Cd in household dust from rural areas was 3.29 times of that from urban areas, while the SWC of Ni from urban areas was 3.71 times of that from rural areas. The results showed that four principal components were extracted, and the cumulative contribution rate reached 79.127%. The exposure dose of 13 metals to children aged 2-3 years was presented with the highest by ingestion. Metals such as Fe, Zn, and Mn posed inevitable health risk to children with high exposure. Countermeasures should be carried out to minimize the children exposure to metals in household dust urgently, such as the establishment of environmental health standard for household dust.

Effect of the phthalates exposure on sex steroid hormones in the US population.

BACKGROUND: New alternative phthalates have been increasingly substituted for certain phthalates in some consumer products due to safety concerns. However, research on the steroidal effect of exposure to the newer replacement phthalates in the general adult population is lacking. OBJECTIVES: This study aimed to examine the associations of exposure to the older generation and newer replacement phthalates with sex hormone levels in the U.S. general population. METHODS: The current cross-sectional study was based on the National Health and Nutrition Examination Survey (NHANES) 2015-2016. Sixteen urinary phthalates metabolites and three serum sex hormones were measured in 1768 adults. Gender-specific associations between urinary phthalate concentrations and sex hormones were estimated by using adjusted multiple linear regression. Logistic regression was performed to calculate the risk of phthalates exposure on hormones dysfunction. RESULTS: Most phthalates metabolites concentrations were lower than 50 ng/mL. MEP, MBP, MiBP, MECPP, MCOP, MEHHP, MEOHP were higher than others, suggesting that new alternative DEP, DBP, and DiNP were exposed at high levels in daily life while DINCH was at a low level. Phthalates exposure was associated with decreased testosterone levels and increased estradiol and SHBG in total samples. Testosterone level was negatively associated with MnBP (ß: -0.05, 95% CI: -0.09, 0), MEOHP (ß:-0.05, 95% CI:-0.09,-0.01), MEHHP (ß:-0.04, 95% CI:-0.08,0), MECPP (ß:-0.07, 95% CI:-0.11,-0.03), MEP (ß: -0.03, 95% CI: -0.06, 0), MiBP (ß: -0.05, 95% CI: -0.10, -0.01) in males; ln-transformed estradiol were increased by 0.18 pg/mL (95% CI: 0.05,0.31), 0.15 pg/mL (95% CI: 0.01,0.29) with each 1 ln-concentration increase in MEHP and MNP, respectively, in females. CONCLUSIONS: Our results suggest that phthalates exposure may disturb the hormone homeostasis in adults. The safe alternative should be used with caution in industrial production in the future and the need for further research into the safety of the new alternative replacements is necessary.

Exploring the impact of new particle formation events on PM2.5 pollution during winter in the Yangtze River Delta, China.

New particle formation (NPF) events are an increasingly interesting topic in air quality and climate science. In this study, the particle number size distributions, and the frequency of NPF events over Hefei were investigated from November 2018 to February 2019. The proportions of the nucleation mode, Aitken mode, and accumulation mode were 24.59%, 53.10%, and 22.30%, respectively, which indicates the presence of abundant ultrafine particles in Hefei. Forty-six NPF events occurred during the observation days, accounting for 41.82% of the entire observation period. Moreover, the favorable meteorological conditions, potential precursor gases, and PM2.5 range of the NPF events were analyzed. Compared to non-NPF days, the NPF events preferentially occurred on days with lower relative humidity, higher wind speeds, and higher temperatures. When the PM2.5 was 15-20, 70-80, and 105-115 µg/m3, the frequency of the NPF events was higher. Nucleation mode particles were positively related to atmospheric oxidation indicated by ozone when PM2.5 ranged from 15 to 20 µg/m3, and related to gaseous precursors like SO2 and NO2 when PM2.5 was located at 70-80 and 105-115 µg/m3. On pollution days, NPF events did not directly contribute to the increase in the PM2.5 in the daytime, however, NPF events would occur during the night and the growth of particulate matter contributes to the nighttime PM2.5 contents. This could lead to pollution that lasted into the next day. These findings are significant to the improvement of our understanding of the effects of aerosols on air quality.

Expression and role of anti-oxidative damage factors in the placenta of preterm infants with premature rupture of membranes. / æŠ—æ°§åŒ–æŸä¼¤å› å­åœ¨èƒŽè†œæ—©ç ´æœªè¶³æœˆå„¿èƒŽç›˜ä¸­çš„è¡¨è¾¾åŠä½œç”¨.

OBJECTIVES: To study the association of the anti-oxidative damage factors nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) with preterm premature rupture of membranes (PPROM). METHODS: A prospective study was conducted. The neonates who were hospitalized in Yanbian Hospital from 2019 to 2020 were enrolled as subjects, among whom there were 30 infants with PPROM, 32 infants with term premature rupture of membranes (TPROM), and 35 full-term infants without premature rupture of membranes (PROM). Hematoxylin and eosin staining was used to observe the inflammatory changes of placental tissue. Immunohistochemical staining was used to measure the expression of Nrf2, HO-1, and NQO1 in placental tissue. Western blot was used to measure the protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue. RESULTS: Compared with the PPROM group, the TPROM group and the non-PROM full-term group had significantly higher positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue (P<0.05). There were no significant differences in the positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue between the TPROM and non-PROM full-term groups (P>0.05). CONCLUSIONS: The low expression levels of Nrf2, HO-1, and NQO1 in placental tissue may be associated with PPROM, suggesting that anti-oxidative damage is one of the directions to prevent PPROM.

Characterization and exposure assessment of household fine particulate matter pollution in China.

Household fine particulate matter (PM2.5 ) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 µg/m3 . HPL in the rural area (164.3 ± 104.5 µg/m3 ) was higher than that in the urban area (123.9 ± 122.3 µg/m3 ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 µg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.

Polyaspartic acid alleviates cadmium toxicity in rapeseed leaves by affecting cadmium translocation and cell wall fixation of cadmium.

Polyaspartic acid (PASP) is a macromolecule compound with carboxylic acid side chains which is polymerized by L-aspartic acid, has been used as a biodegradable and environmentally-friendly chelating agent to enhance the phytoremediation of heavy metal-contaminated soils. Cadmium (Cd) is a toxic element for plant growth, productivity, and food security. To reveal the responses of PASP to plant physiology and morphology under Cd stress, we comprehensively analyzed soil characteristics, cell ultrastructure, reactive oxygen species (ROS), antioxidant enzymes, Cd uptake, transport, subcellular distribution, cell wall compositions, and their Cd chelating capacity in rapeseed. The results showed PASP increased the content of total N, total P, and available P in soil by 3.4%, 28.6%, and 39.8%, respectively, but did not change soil pH and available Cd. Meanwhile, PASP promoted dry mass accumulation and increased photosynthetic pigment content in rapeseed leaves by maintaining the chloroplast structure. Lower malondialdehyde (MDA) content and hydrogen peroxide (H2O2) accumulation and activated antioxidant enzymes in leaves indicate that PASP contributed to relieving Cd-induced oxidative damage to cells of rapeseed leaves. The results indicated that PASP application increased the Cd distribution ratio in root cell walls from 47.4% to 62.3% and decreased the Cd content in xylem sap by 37.8%, which ultimately reduced Cd reallocation in leaves. Additionally, higher pectin content and Cd in pectin resulted in higher Cd retention in leaf cell walls while reducing its concentration in the organelle fraction. The results indicated that 0.3% PASP effectively alleviated Cd stress in rapeseed leaves by inhibiting Cd transportation from roots, activating antioxidant enzymes to scavenge ROS, and promoting Cd chelation by cell wall pectin in leaves.

Characteristic analysis of continuous new particle formation events in Hefei: A case study of the May Day holiday in China.

Studying the characteristics of new particle formation (NPF) is conducive to exploring the impact of atmospheric particulate matter on the climate, environment, and human health. The particle number size distributions (5.6-560 nm) of aerosols were measured using a fast mobility particle sizer (FMPS) from 1 to 11 May 2019. The clean atmosphere was one of the basic conditions for the occurrence of this continuous new particle formation events. It started between 9:00 and 12:00, and it mainly ended after 20:00. The growth rate (GR) and condensation sink (CS) values in Hefei were 2.98 ± 0.97 nm·h-1 and (3.0 ± 0.4) × 10-2 s-1, respectively. Back trajectory clustering analysis revealed that the mass concentration of the air masses from the southeastern part of Henan Province and the southern part of Anhui Province surrounding the study area were relatively high. The analysis results of the potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) methods show that in addition to local pollution, the long-distance transport of pollutants in the Yangtze River Delta (YRD) greatly contributed to the accumulation modal particulate concentration in Hefei. Moreover, the population affected by PM2.5 during the observation period reached 8.19 × 104, accounting for 1.08% to the total population in Hefei. The premature death cases associated with PM2.5 reached 8.35 × 102. This study is helpful to understand the main influencing factors of consecutive NPF events and the health risks of fine particles.

CLDN6 Suppresses c-MYC-Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer.

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c-MYC-mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co-activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c-MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c-MYC-mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

Engineering Herbicide-Tolerance Rice Expressing an Acetohydroxyacid Synthase with a Single Amino Acid Deletion.

The acetohydroxyacid synthase (AHAS) is an essential enzyme involved in branched amino acids. Several herbicides wither weeds via inhibiting AHAS activity, and the AHAS mutants show tolerance to these herbicides. However, most AHAS mutations are residue substitutions but not residue deletion. Here, residue deletion was used to engineering the AHAS gene and herbicide-tolerant rice. Molecular docking analysis predicted that the W548 of the AHAS was a residue deletion to generate herbicide tolerance. The AHAS-ΔW548 protein was generated in vitro to remove the W548 residue. Interestingly, the deletion led to the tetramer dissociation of the AHAS, while this dissociation did not reduce the activity of the AHAS. Moreover, the W548 deletion contributed to multi-family herbicides tolerance. Specially, it conferred more tolerance to sulfometuron-methyl and bispyribac-sodium than the W548L substitution. Further analysis revealed that AHAS-ΔW548 had the best performance on the sulfometuron-methyl tolerance compared to the wild-type control. Over-expression of the AHAS-ΔW548 gene into rice led to the tolerance of multiple herbicides in the transgenic line. The T-DNA insertion and the herbicide treatment did not affect the agronomic traits and yields, while more branched-chain amino acids were detected in transgenic rice seeds. Residue deletion of W548 in the AHAS could be a useful strategy for engineering herbicide tolerant rice. The increase of branched-chain amino acids might improve the umami tastes of the rice.

Controlled synthesis of 2D Mo2C/graphene heterostructure on liquid Au substrates as enhanced electrocatalytic electrodes.

2D Mo2C has drawn considerable interest recently for its excellent properties in 2D superconductivity and enhanced hydrogen evolution reaction (HER). Liquid metals have been demonstrated to be an ideal substrate for large-area 2D Mo2C growth. However, the growth mechanism of 2D Mo2C on liquid metals has rarely been explored. Here we report the synthesis of high-quality 2D Mo2C crystals and Mo2C/graphene heterostructures on liquid Au by chemical vapor deposition method. A sunk growth mode of 2D Mo2C on liquid Au substrates has revealed, by atomic force microscope characterizations, that some Mo2C crystals grow below the level of Au terraces around tens of nanometers. Furthermore, graphene/Mo2C heterostructure is controllably synthesized by tuning the hydrogen/carbon ratio, which is proven to be an enhanced electrocatalyst for HER against pure Mo2C crystal grown on liquid Au substrates.

Exendin-4 Exacerbates Burn-Induced Morbidity in Mice by Activation of the Sympathetic Nervous System.

BACKGROUND: Although glucagon-like peptide 1- (GLP-1-) based therapy of hyperglycemia in burn injury has shown great potential in clinical trials, its safety is seldom evaluated. We hypothesize that exendin-4, a GLP-1 analogue, might affect the immune response via the activation of the sympathetic nervous system in burn injury. METHODS: Male Balb/c mice were subjected to sham or thermal injury of 15% total body surface area. Exendin-4 on T cell function in vitro was examined in cultured splenocytes in the presence of ß-adrenoceptor antagonist propranolol (1 nmol/L) or GLP-1R antagonist exendin (9-39) (1 µmol/L), whereas its in vivo effect was determined by i.p. injection of exendin-4 (2.4 nmol/kg) in mice. To further elucidate the sympathetic mechanism, propranolol (30 mg/kg) or vehicle was applied 30 min prior to injury. RESULTS: Although the exacerbated burn-induced mortality by exendin-4 was worsened by propranolol pretreatment, the inhibition of T cell proliferation by exendin-4 in vitro could be restored by propranolol instead of exendin (9-39). However, a Th2 switch by exendin-4 in vitro could only be reversed by exendin (9-39). Likewise, the inhibition of splenic T cell function and NFAT activity by exendin-4 in vivo was restored by propranolol. By contrast, the increased splenic NF-κB translocation by exendin-4 in vivo was potentiated by propranolol in sham mice but suppressed in burn mice. Accordingly, propranolol abrogated the heightened inflammatory response in the lung and the accelerated organ injuries by exendin-4 in burn mice. On the contrary, a Th2 switch and higher serum levels of inflammatory mediators by exendin-4 were potentiated by propranolol in burn mice. Lastly, exendin-4 raised serum stress hormones which could be remarkably augmented by propranolol. CONCLUSIONS: Exendin-4 suppresses T cell function and promotes organ inflammation through the activation of the sympathetic nervous system, while elicits Th2 switch via GLP-1R in burn injury.