Photosynthetic plasticity aggravates the susceptibility of magnesium-deficient leaf to high light in rapeseed plants: the importance of Rubisco and mesophyll conductance.

Plants grown under low magnesium (Mg) soils are highly susceptible to encountering light intensities that exceed the capacity of photosynthesis (A), leading to a depression of photosynthetic efficiency and eventually to photooxidation (i.e., leaf chlorosis). Yet, it remains unclear which processes play a key role in limiting the photosynthetic energy utilization of Mg-deficient leaves, and whether the plasticity of A in acclimation to irradiance could have cross-talk with Mg, hence accelerating or mitigating the photodamage. We investigated the light acclimation responses of rapeseed (Brassica napus) grown under low- and adequate-Mg conditions. Magnesium deficiency considerably decreased rapeseed growth and leaf A, to a greater extent under high than under low light, which is associated with higher level of superoxide anion radical and more severe leaf chlorosis. This difference was mainly attributable to a greater depression in dark reaction under high light, with a higher Rubisco fallover and a more limited mesophyll conductance to CO2 (gm ). Plants grown under high irradiance enhanced the content and activity of Rubisco and gm to optimally utilize more light energy absorbed. However, Mg deficiency could not fulfill the need to activate the higher level of Rubisco and Rubisco activase in leaves of high-light-grown plants, leading to lower Rubisco activation and carboxylation rate. Additionally, Mg-deficient leaves under high light invested more carbon per leaf area to construct a compact leaf structure with smaller intercellular airspaces, lower surface area of chloroplast exposed to intercellular airspaces, and CO2 diffusion conductance through cytosol. These caused a more severe decrease in within-leaf CO2 diffusion rate and substrate availability. Taken together, plant plasticity helps to improve photosynthetic energy utilization under high light but aggravates the photooxidative damage once the Mg nutrition becomes insufficient.

Photo-thermal synergistic excitation: Feasible strategy to detect ethanol for wide bandgap ZIF-8 at low work temperature.

Zeolitic Imidazolate Framework-8 (ZIF-8) material was prepared by chemical precipitation method. The microstructure and physical properties of the as-prepared samples were characterized by XRD, BET, FESEM and UV spectrophotometer. The self-made four-channel measurement device was used to test the gas sensitivity of ZIF-8 material toward ethanol gas under photo-thermal synergistic excitation. The results showed that the sample was typical ZIF-8 (Eg = 4.96 eV) with a regular dodecahedron shape and the specific surface is up to 1793 m2/g. The as-prepared ZIF-8 has a gas response value of 55.04 to 100 ppm ethanol at 75°C and it shows good gas sensing selectivity and repeated stability. The excellent gas sensitivity can be attributed to the increase of free electron concentration in the ZIF-8 conduction band by photo-thermal synergistic excitation, and the large specific surface area of ZIF-8 material provides more active sites for gas-solid surface reaction. The reaction mechanism of ZIF-8 material under multi-field excitation was also discussed.

Clinical efficacy of low-dose glucocorticoid therapy for critically ill patients with severe fever with thrombocytopenia syndrome: A retrospective cohort study.

OBJECTIVES: To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment. METHODS: A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models. RESULTS: A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log10(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts. CONCLUSION: Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.

Sufficient potassium improves inorganic phosphate-limited photosynthesis in Brassica napus by enhancing metabolic phosphorus fractions and Rubisco activity.

Crop photosynthesis (A) and productivity are often limited by a combination of nutrient stresses, such that changes in the availability of one nutrient may affect the availability of another nutrient, in turn influencing A. In this study, we examined the synergistic effects of phosphorus (P) and potassium (K) on leaf A in a nutrient amendment experiment, in which P and K were added individually or in combination to Brassica napus grown under P and K co-limitation. The data revealed that the addition of P gradually removed the dominant limiting factor (i.e. the limited availability of P) and improved leaf A. Strikingly, the addition of K synergistically improved the overall uptake of P, mainly by boosting plant growth, and compensated for the physiological demand for P by prioritizing investment in metabolic pools of P (P-containing metabolites and inorganic phosphate, Pi). The enlarged pool of metabolically active P was partially associated with the upregulation of Pi regeneration through release from triose phosphates rather than replacement of P-containing lipids. This process mitigated P restrictions on A by maintaining the ATP/NADPH and NADPH/NADP+ ratios and increasing the content and activity of Rubisco. Our findings demonstrate that sufficient K increased Pi-limited A by enhancing metabolic P fractions and Rubisco activity. Thus, ionic synergism may be exploited to mitigate nutrient-limiting factors to improve crop productivity.

Chromatin remodeler Dmp18 regulates apoptosis by controlling H2Av incorporation in Drosophila imaginal disc development.

Programmed Cell Death (PCD) or apoptosis is a highly conserved biological process and plays essential roles both in the development and stress context. In Drosophila, expression of pro-apoptotic genes, including reaper (rpr), head involution defective (hid), grim, and sickle (skl), is sufficient to induce cell death. Here, we demonstrate that the chromatin remodeler Dmp18, the homolog of mammalian Znhit1, plays a crucial role in regulating apoptosis in eye and wing development. We showed that loss of Dmp18 disrupted eye and wing development, up-regulated transcription of pro-apoptotic genes, and induced apoptosis. Inhibition of apoptosis suppressed the eye defects caused by Dmp18 deletion. Furthermore, loss of Dmp18 disrupted H2Av incorporation into chromatin, promoted H3K4me3, but reduced H3K27me3 modifications on the TSS regions of pro-apoptotic genes. These results indicate that Dmp18 negatively regulates apoptosis by mediating H2Av incorporation and histone H3 modifications at pro-apoptotic gene loci for transcriptional regulation. Our study uncovers the role of Dmp18 in regulating apoptosis in Drosophila eye and wing development and provides insights into chromatin remodeling regulating apoptosis at the epigenetic levels.

Coinfections in hospitalized patients with severe fever with thrombocytopenia syndrome: A retrospective study.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.

Thrombocytopenia and increased risk of adverse outcome in COVID-19 patients.

Background: Thrombocytopenia was common in the coronavirus disease 2019 (COVID-19) patients during the infection, while the role of thrombocytopenia in COVID-19 pathogenesis and its relationship with systemic host response remained obscure. The study aimed to systematically evaluate the relationship between thrombocytopenia in COVID-19 patients and clinical, haematological and biochemical markers of the disease as well as adverse outcomes. Methods: To assess the relationship between abnormal platelet levels and disease progression, a multi-center retrospective cohort study was conducted. COVID-19 patients with thrombocytopenia and a sub-cohort of matched patients without thrombocytopenia were compared for their clinical manifestations, haematological disorders, biochemical parameters, inflammatory markers and clinical outcome. Results: Thrombocytopenia was present in 127 of 2,209 analyzed patients on admission. Compared with the control group, thrombocytopenia patients developed significantly higher frequency of respiratory failure (41.9% vs. 22.6%, P = 0.020), intensive care unit entrance (25.6% vs. 11.5%, P = 0.012), disseminated intravascular coagulation (45.2% vs. 10.6%, P < 0.001), more altered platelet morphology indexes and coagulation perturbation, higher levels of inflammatory markers. In addition, a significantly increased all-cause mortality (hazard ratio 3.08, 95% confidence interval 2.26-4.18, P < 0.001) was also observed in the patients with thrombocytopenia. Late development of thrombocytopenia beyond 14 days post-symptom was observed in 61 patients, from whom a comparable mortality rate yet longer duration to death was observed compared to those with early thrombocytopenia. Conclusions: Our finding from this study adds to previous evidence that thrombocytopenia is associated with adverse outcome of the disease and recommend that platelet count and indices be included alongside other haematological, biochemical and inflammatory markers in COVID-19 patients' assessment during the hospital stay.

Potassium availability influences the mesophyll structure to coordinate the conductance of CO2 and H2 O during leaf expansion.

Leaf growth relies on photosynthesis and hydraulics to provide carbohydrates and expansion power; in turn, leaves intercept light and construct organism systems for functioning. Under potassium (K) deficiency stress, leaf area, photosynthesis and hydraulics are all affected by alterations in leaf structure. However, the connection between changes in leaf growth and function caused by the structure under K regulation is unclear. Consequently, the leaf hydraulic conductance (Kleaf ) and photosynthetic rate (A) combined with leaf anatomical characteristics of Brassica napus were continuously observed during leaf growth under different K supply levels. The results showed that Kleaf and A decreased simultaneously after leaf area with the increasing K deficiency stress. K deficiency significantly increased longitudinal mesophyll cell investment, leading to a reduced volume fraction of intercellular air-space (fias ) and decreased leaf expansion rate. Furthermore, reduced fias decreased mesophyll and chloroplast surfaces exposed to intercellular airspace and gas phase H2 O transport, which induced coordinated changes in CO2 mesophyll conductance and hydraulic conductance in extra-xylem pathways. Adequate K supply facilitated higher fias through smaller palisade tissue cell density (loose mesophyll cell arrangement) and smaller spongy tissue cell size, which coordinated CO2 and H2 O conductance and promoted leaf area expansion.

Plasma glucose levels and diabetes are independent predictors for mortality in patients with COVID-19.

This study is performed to figure out how the presence of diabetes affects the infection, progression and prognosis of 2019 novel coronavirus disease (COVID-19), and the effective therapy that can treat the diabetes-complicated patients with COVID-19. A multicentre study was performed in four hospitals. COVID-19 patients with diabetes mellitus (DM) or hyperglycaemia were compared with those without these conditions and matched by propensity score matching for their clinical progress and outcome. Totally, 2444 confirmed COVID-19 patients were recruited, from whom 336 had DM. Compared to 1344 non-DM patients with age and sex matched, DM-COVID-19 patients had significantly higher rates of intensive care unit entrance (12.43% vs. 6.58%, P = 0.014), kidney failure (9.20% vs. 4.05%, P = 0.027) and mortality (25.00% vs. 18.15%, P < 0.001). Age and sex-stratified comparison revealed increased susceptibility to COVID-19 only from females with DM. For either non-DM or DM group, hyperglycaemia was associated with adverse outcomes, featured by higher rates of severe pneumonia and mortality, in comparison with non-hyperglycaemia. This was accompanied by significantly altered laboratory indicators including lymphocyte and neutrophil percentage, C-reactive protein and urea nitrogen level, all with correlation coefficients >0.35. Both diabetes and hyperglycaemia were independently associated with adverse prognosis of COVID-19, with hazard ratios of 10.41 and 3.58, respectively.

Potassium regulates diel leaf growth of Brassica napus by coordinating the rhythmic carbon supply and water balance.

Carbon and water are two main factors limiting leaf expansion. Restriction of leaf growth by low availability of carbon or water is among the earliest visible effects of potassium (K) deficiency. It is not known how K is involved in regulating the rhythmic supply of these two substrates, which differ remarkably across the day-night cycle, affecting leaf expansion. We investigated the effects of different K regimes on the time courses of leaf expansion, carbon assimilation, carbohydrates, and hydraulic properties of Brassica napus. Potassium supply increased leaf area, predominantly by promoting night-time leaf expansion (>60%), which was mainly associated with increased availability of carbohydrates from photosynthetic carbon fixation and import from old leaves rather than improvement of leaf hydraulics. However, sufficient K improved leaf hydraulic conductance to balance diurnal evaporative water loss and increase the osmotic contribution of water-soluble carbohydrates, thereby maintaining leaf turgor and increasing the daytime expansion rate. The results also indicated an ontogenetic role of K in modifying the amplitude of circadian expansion; almost 80% of the increase in leaf area occurred before the area reached 66.9% of the mature size. Our data provide mechanistic insight into K-mediated diel coordination of rhythmic carbon supply and water balance in leaf expansion.

Combination of oridonin and TRAIL induces apoptosis in uveal melanoma cells by upregulating DR5.

AIM: To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and oridonin on choroidal melanoma cell lines, and to explore its underlying mechanism. METHODS: MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin, and MTT assay used to evaluate the inhibition rate of the two compounds on cells. Then, the cell cycle distribution and apoptosis were detected by flow cytometry, and changes in apoptosis-related proteins such as death receptor 5 (DR5), a-caspase-3, and x-linked inhibitor of apoptosis protein (XIAP) were detected by Western blot. MUM-2B cells were transfected with si-DR5, which interfered with the expression of the DR5 gene. MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins. RESULTS: When TRAIL and oridonin were simultaneously administered to the MUM-2B cells, the apoptosis rate was significantly higher than that by the two drugs individually. However, the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone. Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells. The Western blot results showed that the protein expression levels of the DR5, a-caspase-3, and BAX increased, while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells. Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells. CONCLUSION: The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment, which may ascribe to up-regulation of DR5.

Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China.

BACKGROUND: Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region. METHODS: A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates. RESULTS: Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334-4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261-3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002-2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271-5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419-4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced. CONCLUSIONS: Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

Single-cell landscape of peripheral immune responses to fatal SFTS.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high fatality. Poor prognosis of SFTS has been associated with dysregulated host immunity; however, the immune patterns associated with pathophysiology involving SFTS exacerbation remain unclear. Here, we show that the single-cell landscape of peripheral immune responses is reprogrammed in SFTS and characterized by monocyte shift to an intermediate type along with complement activation, perturbation of plasmablast composition, and highly exhausted T cells, all correlated with lethal consequences. We identify the overexpression of interferon (IFN)-stimulated genes across most immune cell types after SFTSV infection, which are simultaneously related to older age, high viremia, and a hyperinflammatory response. A retrospective clinical study reveals no efficiency of IFN-α in treating SFTS. These data collectively support the intermediate monocytes and IFN-I-inducible plasmablasts to be major targets for SFTS virus infection, and they indicate the pivotal role of the IFN-I response in exacerbating hyperinflammation and lethal SFTS.

Characteristics of balance performance in the Chinese elderly by age and gender.

BACKGROUND: Population aging has been an emerging public and health concern globally. Balance performance can be applied as an indicator of functional status and a predictor of health outcomes in the elderly. However, reference data of balance performance in the elderly generated from large scale studies have been very limited. In research and geriatric assessment settings, the age and gender specific data on balance performance are indispensable prerequisites for identifying subpopulation with and at risk of impairments and subsequently implementing targeted interventions in clinics and public health to improve their balance performance. METHODS: A total of 1984 elderly subjects aged 60 to 97 years from community settings in urban China were investigated. The balance performances together with 3 individual domains and 16 items were evaluated using the X16 balance testing scale. RESULTS: In the elderly, with age increases each item, individual domain, and overall balance performance scores decreased gradually. Meanwhile, individual variations of individual domains and overall balance performance were all increased over age. Relative to levels of 60- years, postural stability and overall balance performance decreased significantly since 65 years old, static balance and dynamic balance capacities started to decrease significantly since 70 years old. There was no significant difference in each balance domain and overall balance performance between men and women. Across age groups, portions of individuals able to perform task 4, 8 and 11 successfully were the lowest amongst their corresponding domains static balance, postural stability, and dynamic balance, respectively. Similar patterns were observed in both men and women. Balance performances were categorized into poor, fair, and good groups with scores of 0 to 10, 11 to 17, and 18 to 20, respectively. With increases of age, proportions with poor and fair balance capacities elevated stably. CONCLUSIONS: In the elderly, with advances in age, abilities of overall balance performance, individual domains of static balance, postural stability, and dynamic balance, and successful performances on specific tasks declined gradually and stably. The deterioration started to be obvious since 65-75 years. Men and women had similar patterns.

A systematic meta-analysis of immune signatures in patients with COVID-19.

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.

Erratum: Expression of ywhaz and gene regulation network in hepatocellular carcinoma.

[This corrects the article DOI: 10.3892/ol.2020.11481.].

Expression of yhwaz and gene regulation network in hepatocellular carcinoma.

The adaptor protein 14-3-3ζ is encoded by the yhwaz gene and implicated in a wide range of biological processes. In tumorigenesis, 14-3-3ζ recognizes specific phosphorylation motifs and interacts with hundreds of target proteins and is, thus, involved in the regulation of tumor proliferation, migration and differentiation. In the present study, bioinformatics tools were used to analyze data from The Cancer Genome Atlas and Gene Expression Omnibus databases and the expression of yhwaz, and gene regulation networks were identified as potentially relevant in hepatocellular carcinoma (HCC). In HCC, yhwaz expression was demonstrated to be upregulated and significantly associated with poor prognosis. Expression levels of microRNAs targeting yhwaz were associated with improved prognosis in patients with liver cancer. Gene networks that are regulated by yhwaz were found to be involved in cell cycle regulation and tumorigenesis, indicating the potential use of the expression levels of yhwaz in liver tissue as predictive biomarkers in patients with liver cancer. In the present study, yhwaz was identified as a gene of interest through data mining gene expression databases and its involvement in regulatory networks in HCC was indicated. Therefore, further in vitro and in vivo studies on the role of yhwaz in the carcinogenesis of HCC would be greatly beneficial.

Arsenic induces transgenerational behavior disorders in Caenorhabditis elegans and its underlying mechanisms.

The present study aimed to identify the effects of arsenic on behaviors in Caenorhabditis elegans (C. elegans) and the transgenerational effects. The synchronized C. elegans (P generation) were exposed to 0, 0.2, 1.0, and 5.0 mM NaAsO2 and the subsequent generations (F1 and F2) were maintained on fresh nematode growth medium (NGM). The behaviors and growth were recorded at 0, 12, 24, 36, 48, 60, and 72 h post synchronization. The results demonstrated that arsenic affected various indicators regarding the behavior (head thrash, body bend, movement speed, wavelength, amplitude and so on) and in general the effects started to accumulate from 24 h and lasted throughout the exposure. The behavior impairments were transgenerational with varying patterns, amongst the head thrash and body bend responded most sensitively though the responses gradually declined across generations. Arsenic exposure inhibited the growth (body length, body width, and body area) in P C. elegans from 24 h to 60 h, however there was no difference between treatments groups and the control at 72 h. Arsenic led to a dose-dependent degeneration of dopaminergic neurons in C. elegans, and inhibition of BAS-1 and CAT-2 expressions. The expressions of GCS-1, GSS-1, and SKN-1 were induced by arsenic exposure. Overall, chronic arsenic exposure impaired the behaviors and there were transgenerational effects. The head thrash and body bend responded most sensitively. Arsenic induced behavioral disorders might be attributed to degeneration of dopaminergic neurons which was associated with oxidative stress.

DJ-1 inhibits autophagy activity of prostate cancer cells by repressing JNK-Bcl2-Beclin1 signaling.

The regulation of DJ-1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ-1 could alter autophagy and regulate Beclin1-involved autophagy response through JNK-dependent pathway. JNK is known to mediate autophagy through Bcl2-Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ-1-modulated PCa cells. The current studies showed that DJ-1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ-1 knockdown exerted the opposite effect. Moreover, DJ-1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3-MA. In addition, DJ-1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ-1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ-1-overexpressed LNCaP while increasing LC3 transformation and LC3-puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin-1). In contrast, when DJ-1 was silenced, the death of LNCaP, LC3 transformation, and LC3-puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ-1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK-Bcl2-Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ-1 in the development of PCa.

Transfection Efficiency Evaluation and Endocytosis Exploration of Different Polymer Condensed Agents.

DNA condensed agents can improve the transfection efficiency of the cationic liposome delivery system. However, various condensed agents have distinct transfection efficiency and cellular cytotoxicity. The object of this study was to screen the optimal agents with the high transfection efficiency and low cytotoxicity from four polymer compressive materials, polyethylenimine (PEI), chitosan, poly-l-lysine (PLL), and spermidine. DNA was precompressed with these four agents and then combined to cationic liposomes. Subsequently, the entrapment and transfection efficiency of the obtained complexes were investigated. Finally, the particle sizes, cytotoxicity, and endocytosis fashion of these copolymers (Lipo-PEI, Lipo-chitosan, Lipo-PLL, and Lipo-spermidine) were examined. It was found that these four copolymers had significantly lower cytotoxicity and higher transfection efficiency (45.5%, 42.4%, 36.8%, and 47.4%, respectively) than those in the control groups. The transfection efficiency of Lipo-PEI and Lipo-spermidine copolymers were better than the other two copolymers. In 293T cells, nystatin significantly inhibited the transfection efficiency of Lipo-PEI-DNA and Lipo-spermidine-DNA (51.88% and 46.05%, respectively), which suggest that the endocytosis pathway of Lipo-spermidine and Lipo-PEI copolymers was probably caveolin dependent. Our study indicated that these dual-degradable copolymers especially liposome-spermidine copolymer could be used as the potential biocompatible gene delivery carriers.