Arabidopsis ERD15 regulated by BBX24 plays a positive role in UV-B signaling.

Ultraviolet-B (UV-B, 280-315 nm) is a minor component of solar radiation, but it has a major regulatory impact on plant growth and development. Solar UV-B regulates numerous aspects of plant metabolism, morphology and physiology through altering the expression of hundreds of genes. EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15) is a drought-induced rapid response gene, formerly known as a negative regulator of the abscisic acid (ABA) signaling pathway. It is unclear whether ERD15 is involved in UV-B-induced photomorphogenesis. Previously, we reported that the BBX24 transcriptional factor negatively regulated UV-B signaling. In the present study, we identified that ERD15 is involved in UV-B photomorphogenesis as a positive regulator at phenotypic, physiological and molecular levels. Our results indicated that ERD15 expression is suppressed by UV-B, inhibited the elongation of Arabidopsis hypocotyls in a UV-B-dependent manner, promoted the expression of related UV-B signaling genes and increased the total antioxidant capacity of Arabidopsis under UV-B. Genetic hybridization results show that ERD15 acts downstream of BBX24, and BBX24 protein mediated the expression of ERD15 by binding to its promoter. Thus, ERD15 is a novel positive regulator of the UV-B signaling pathway, which is downstream of BBX24 and regulated by BBX24 protein to participate in UV-B photomorphogenesis.

Morphological, molecular, and life cycle characteristics of Phaeocystis globosa Scherffel (Prymnesiophyceae) in the Southeast China Sea.

Phaeocystis globosa blooms frequently occur in the Southeast China Sea and cause significant negative impacts on coastal ecology and mariculture. The P. globosa blooms in southeastern China are very different compared to those of European strains, suggesting that differences may exist in their morphological, phylogenetic, and life history traits. In this study, seven strains of P. globosa isolated from Southeast China Sea that were typical strains of algal blooms in the region, in addition to one strain from the Gulf of Mexico (CCMP629), were comprehensively evaluated to better understand region-specific differences of the species. Significant differences were not observed in the internal cell structures and other characteristics compared to those of European strains, while differences in cell surface structures were apparent. For example, small and large flagellated Chinese P. globosa cells exhibited two flagella with slightly unequal lengths and a short haptonema, the surfaces of small flagellated cells were not covered by scales, and colony cell diameters were smaller. 18S rRNA sequence phylogenetic analysis also revealed that P. globosa comprised a species complex with two ecotypes (warm- and cold-water types), of which the strains from the southeastern coast of China and CCMP629 belonged to the warm-water type. In addition, the life cycles and variable modes of P. globosa colony formation were evaluated in detail. The algal bloom may be due to the rapid colonies formation by budding and colony fragments. These results provide new insights into the life cycle of P. globosa and highlight the differences in morphological and phylogenetic relationships between strains from the southeast coast of China and those from coastal European regions.

Autophagy in homocysteine­induced HUVEC senescence.

The senescence of vascular endothelial cells (VECs) drives the occurrence and development of cardiovascular disease (CVD). Homocysteine (HCY) is a general risk factor for age-associated CVDs. Autophagy, an evolutionarily conserved lysosomal protein degradation pathway, serves a part in VEC senescence. The purpose of this study was to investigate the role of autophagy in HCY-induced endothelial cell senescence and explore novel mechanisms and therapeutic approaches for related CVDs. Human umbilical vein endothelial cells (HUVECs) were isolated from fresh umbilical cords of healthy pregnancies. Cell Counting Kit-8, flow cytometry and senescence-associated (SA) ß-galactosidase (Gal) staining demonstrated that HCY induced HUVEC senescence by decreasing cell proliferation, arresting cell cycle and increasing the number of SA-ß-Gal-positive cells. Stub-RFP-Sens-GFP-LC3 autophagy-related double fluorescence lentivirus revealed that HCY increased autophagic flux. Further, inhibition of autophagy using 3-methyladenine increased HCY-induced HUVEC senescence. By contrast, the induction of autophagy via rapamycin alleviated HCY-induced HUVEC senescence. Finally, the detection of reactive oxygen species (ROS) with ROS kit showed that HCY increased intracellular ROS, whereas induction of autophagy reduced intracellular ROS. In conclusion, HCY increased HUVEC senescence and upregulated autophagy; moderate autophagy could reverse HCY-induced cell senescence. Autophagy may alleviate HCY-induced cell senescence by decreasing intracellular ROS. This provides insight into the underlying mechanism of HCY-induced VEC senescence and potential treatments for age-associated CVDs.

Arbuscular mycorrhizal fungi trigger danger-associated peptide signaling and inhibit carbon-phosphorus exchange with nonhost plants.

In soil, arbuscular mycorrhizal fungi (AMF) meet the roots of both host and presumed nonhost plants, but the interactional mechanisms of AMF with and functional relevance for nonhost plants is little known. Here we show AMF can colonize an individually grown nonhost plant, Arabidopsis thaliana, and suppress the growth of Arabidopsis and two nonhost Brassica crops. This inhibitory effect increased with increasing AMF inoculum density, and was independent of AMF species or nutrient availability. 13 C isotope labeling and physiological analyses revealed no significant carbon-phosphorus exchange between Arabidopsis and AMF, indicating a lack of nutritional function in this interaction. AMF colonization activated the danger-associated peptide Pep-PEPR signaling pathway, and caused clear defense responses in Arabidopsis. The impairment of Pep-PEPR signaling in nonhost plants greatly compromised AMF-triggered defensive responses and photosynthesis suppression, leading to higher colonization rates and reduced growth suppression upon AMF inoculation. Pretreatment with Pep peptide decreased AMF colonization, and largely substituted for AMF-induced growth suppression in nonhosts, confirming that the Pep-PEPR pathway is a key participant in resistance to AMF colonization and in mediating growth suppression of nonhost plants. This work greatly increases our knowledge about the functional relevance of AMF and their mechanisms of interactions with nonhost plants.

Molecular subtypes based on PANoptosis-related genes and tumor microenvironment infiltration characteristics in lower-grade glioma.

The growth of cancer, the effectiveness of treatment, and prognosis are all closely related to PANoptosis (include pyroptosis, apoptosis, and necroptosis). It remains unclear whether PANoptosis genes (PANGs) may contribute to lower-grade glioma (LGG) tumor microenvironment (TME). In this study, we collected 1203 LGG samples from three public databases and reported that PANoptosis involves TME interaction and prognosis. Firstly, we provided a comprehensive review of the pan-cancer landscape of PANGs in terms of expression characteristics, prognostic value, mutational profile, and pathway regulation. Then, we identified two distinct PANclusters, each with its own molecular, clinical, and immunological profile. We then developed a scoring system for LGG patients called PANscore. As well as investigating immune characteristics, tumor mutational characteristics, and drug sensitivity, we examined the differences between groups with high PANscores and those with low PANscores. Based on this PANscore and clinicopathological variables, an instant nomogram for predicting clinical survival in LGG patients was developed. Our thorough examination of PANGs in LGG revealed their probable function in TME, as well as their clinicopathological characteristics and prognosis. These discoveries could deepen our comprehension of PANGs in LGG and provide doctors fresh perspectives on how to forecast prognosis and create more efficient, individualized treatment plans.

Thermal adaptation of photosynthetic physiology of the invasive vine Ipomoea cairica (L.) enhances its advantage over native Paederia scandens (Lour.) Merr. in South China.

Ipomoea cairica (L.) Sweet is an invasive vine in South China with strong ecological adaptability in tropical and subtropical ecosystems. However, its invasion mechanism under global warming still remains unknown. In the present study, the thermal adaptability of I. cairica was investigated from the perspective of photosynthetic physiology to explain its successful invasiveness in South China, compared to a niche-overlapping native vine Paederia scandens (Lour.) Merr. Results of field photosynthesis measurements indicated a higher photosynthesis of I. cairica than P. scandens, which was also more temperature-sensitive. Under heat treatment (40 °C), the thermal-avoidance strategy of P. scandens and the thermal-adaptation strategy of the I. cairica enhanced the photosynthetic growth advantage of I. cairica over P. scandens. In I. cairica, the increase of soluble sugar and antioxidant enzyme activity along with the decrease of Malondialdehyde and oxide accumulation demonstrated that I. cairica has superior thermal-adaptation, contrary to P. scandens. Expression of IcOr and IcSRO1 in I. cairica was induced at 40 °C, maintaining the stability of photosynthetic system II and enhancing antioxidant ability. Out study suggested that a higher frequency of heat disturbance under global warming will enhance the invasion capability I. cairica but inhibit the native vine P. scandens. HIGHLIGHT: This paper reveals that contrary thermal-adaptation strategies expanded the photosynthetic, growing, and physiological advantages of invasive I. cairica over native P. scandens under high temperature.

Study on the relationship between genetic polymorphism of reductive folic acid carrier and the risk of neural tube defects.

BACKGROUND: To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. METHODS: The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). RESULTS: The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father's exposure to organic solvents, folic acid deficiency, and mother's diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. CONCLUSION: Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.

A circular RNA derived from GLIS3 accelerates the proliferation of glioblastoma cells through competitively binding with miR-449c-5p to upregulate CAPG and GLIS3.

BACKGROUND: Glioblastoma (GBM) is an aggressive and malignant brain tumor with extremely poor prognosis. Despite advances in treatment, the pathogenesis of GBM remains elusive. Mounting studies have revealed the critical role of circular RNAs (circRNAs) in the development and progression of human cancers including GBM, but the comprehension of their functions is still insufficient. In this study, we investigated the expression profile of a circRNA derived from GLIS family zinc finger 3 (GLIS3) in GBM and normal astrocytes. CircGLIS3 expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Functional experiments were performed to analyze the influence of circGLIS3 on GBM cell proliferation and apoptosis. In addition, mechanism assays were to uncover the potential regulatory mechanism of circGLIS3. RESULTS: CircGLIS3 was up-regulated in GBM cells and knockdown of circGLIS3 significantly hampered proliferation and promoted apoptosis of GBM cells. Furthermore, circGLIS3 positively regulated CAPG and GLIS3 by sponging miR-449c-5p to affect GBM cell proliferation and apoptosis. CONCLUSIONS: In summary, our study identified that circGLIS3 could promote proliferation and inhibit apoptosis of GBM cells via targeting miR-449c-5p/GLIS3/CAPG axis in vitro. This study could offer a novel molecular perspective for further investigation into mechanisms essential to GBM progression.

Comprehensive Analysis of Role of Cyclin-Dependent Kinases Family Members in Colorectal Cancer.

Background: Cyclin-dependent kinases (CDKs) are cell cycle regulators, and abnormal activation can accelerate tumor cell proliferation. However, The relation between CDKs dysregulation to colorectal cancer incidence and progression have not been examined in detail. Methods:Differences in CDKs expression between colorectal cancer and normal tissues, associations between expression and clinical prognosis, incidence and frequencies of CDKs gene mutations, and the influences of CDKs on tumor infiltration by immune cells were examined by analyses of Oncomine, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER databases. Results: Colorectal cancer tissues showed enhanced expression levels of CDKs 1/2/4/5/6/8/12/13/19 but reduced CDK3 expression. CDK7 was highly expressed in some colorectal cancer tissues but downregulated in others. Expression levels of CDK1/3/4/7/8/10/11b/13/18/19/20 were correlated with clinical stage, and CDK 5/10/12/16 expression levels predicted prognosis and survival. Differential CDKs expression correlated with cell cycle progression, amino acid polypeptide modifications, and activation of other protein kinases. Expression levels of all CDKs except CDK16 were correlated with infiltration of CD4+T, CD8+T, B and Tregs cells. Conclusions: CDK 1 and 4 could be used as diagnostic biomarkers for CRC. CDK 5/10/12/16 can be utilized as prognostic biomarkers.

BBX24 Interacts with DELLA to Regulate UV-B-Induced Photomorphogenesis in Arabidopsis thaliana.

UV-B radiation, sensed by the photoreceptor UVR8, induces signal transduction for plant photomorphogenesis. UV-B radiation affects the concentration of the endogenous plant hormone gibberellin (GA), which in turn triggers DELLA protein degradation through the 26S proteasome pathway. DELLA is a negative regulator in GA signaling, partially relieving the inhibition of hypocotyl growth induced by UV-B in Arabidopsis thaliana. However, GAs do usually not work independently but integrate in complex networks linking to other plant hormones and responses to external environmental signals. Until now, our understanding of the regulatory network underlying GA-involved UV-B photomorphogenesis had remained elusive. In the present research, we investigate the crosstalk between the GA and UV-B signaling pathways in UV-B-induced photomorphogenesis of Arabidopsis thaliana. Compared with wild type Landsberg erecta (Ler), the abundance of HY5, CHS, FLS, and UF3GT were found to be down-regulated in rga-24 and gai-t6 mutants under UV-B radiation, indicating that DELLA is a positive regulator in UV-B-induced photomorphogenesis. Our results indicate that BBX24 interacts with RGA (one of the functional DELLA family members). Furthermore, we also found that RGA interacts with HY5 (the master regulator in plant photomorphogenesis). Collectively, our findings suggest that the HY5−BBX24−DELLA module serves as an important signal regulating network, in which GA is involved in UV-B signaling to regulate hypocotyl inhibition.

Knockdown of circ_0055412 promotes cisplatin sensitivity of glioma cells through modulation of CAPG and Wnt/ß-catenin signaling pathway.

INTRODUCTION: Glioma is the most frequent primary cerebral tumor in adults. Recent evidence has suggested that circular RNAs (circRNAs) are associated with the pathological processes in glioma. In our study, we aimed to investigate the function and mechanism of circ_CAPG (circ_0055412) in glioma. METHODS: Firstly, circ_0055412 expression was examined through RT-qPCR analysis. Loss-of-function assays and animal experiments were implemented to evaluate the role of circ_0055412 on cisplatin resistance of glioma cells. Moreover, mechanism assays were done to probe into the regulatory mechanism of circ_0055412 in glioma cells. RESULTS: Circ_0055412 was found to be notably upregulated in glioma cells. Moreover, depletion of circ_0055412 enhanced cisplatin sensitivity of glioma cells in vitro and in vivo. Moreover, circ_0055412 recruited eukaryotic translation initiation factor 4A3 (EIF4A3) protein to stabilize capping actin protein, gelsolin like (CAPG) mRNA. Furthermore, circ_0055412 served as a sponge for microRNA-330-3p (miR-330-3p) and regulated nuclear factor of activated T cells 3 (NFATC3) expression to activate the transcription of catenin beta 1 (CTNNB1), thus participating in the activation of Wnt/ß-catenin signaling pathway. CONCLUSION: Circ_0055412 contributed to cisplatin resistance of glioma cells via stabilizing CAPG mRNA and modulating Wnt/ß-catenin signaling pathway. This finding might provide novel information for the treatment of glioma.

Ferritinophagic Flux Was a Driving Force in Determination of Status of EMT, Ferroptosis, and NDRG1 Activation in Action of Mechanism of 2-Pyridylhydrazone Dithiocarbamate S-Acetic Acid.

Ferritinophagy is a process of ferritin degradation in lysosomes; however, how its effect on other cellular events, such as epithelial-mesenchymal transition (EMT) and ferroptosis remains elusive. In this study, we determined how ferritinophagic flux influence the status of EMT and ferroptosis in HepG2 cell. Our data revealed that 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA) induced EMT inhibition involved ferritinophagy-mediated ROS production, but addition of ferrostatin-1 could attenuate the effect of PdtaA on the regulation of EMT-related proteins, suggesting that ferroptosis might involve in the EMT regulation. Next, downregulation of Gpx4 and xCT as well as enhanced lipid peroxidation further supported that PdtaA was able to induce ferroptosis. Knockdown of NCOA4 significantly attenuated the regulatory effect of PdtaA on related proteins which highlighted that the strength of ferritinophagic flux (NCOA4/ferritin) was a driving force in determination of the status of EMT and ferroptosis. Furthermore, NDRG1 activation was also observed, and knockdown of NDRG1 similarly influenced the expressions of ferroptosis-related proteins, suggesting that NDRG1 also involved ferroptosis induction, which was first reported. Taken together, PdtaA-induced EMT inhibition, ferroptosis, and NDRG1 activation all depended on the strength of ferritinophagic flux.

Effects of Arbuscular Mycorrhizal Fungi on Rice Growth Under Different Flooding and Shading Regimes.

Arbuscular mycorrhizal fungi (AMF) are present in paddy fields, where they suffer from periodic soil flooding and sometimes shading stress, but their interaction with rice plants in these environments is not yet fully explained. Based on two greenhouse experiments, we examined rice-growth response to AMF under different flooding and/or shading regimes to survey the regulatory effects of flooding on the mycorrhizal responses of rice plants under different light conditions. AMF had positive or neutral effects on the growth and yields of both tested rice varieties under non-flooding conditions but suppressed them under all flooding and/or shading regimes, emphasizing the high importance of flooding and shading conditions in determining the mycorrhizal effects. Further analyses indicated that flooding and shading both reduced the AMF colonization and extraradical hyphal density (EHD), implying a possible reduction of carbon investment from rice to AMF. The expression profiles of mycorrhizal P pathway marker genes (GintPT and OsPT11) suggested the P delivery from AMF to rice roots under all flooding and shading conditions. Nevertheless, flooding and shading both decreased the mycorrhizal P benefit of rice plants, as indicated by the significant decrease of mycorrhizal P responses (MPRs), contributing to the negative mycorrhizal effects on rice production. The expression profiles of rice defense marker genes OsPR1 and OsPBZ1 suggested that regardless of mycorrhizal growth responses (MGRs), AMF colonization triggered the basal defense response, especially under shading conditions, implying the multifaceted functions of AMF symbiosis and their effects on rice performance. In conclusion, this study found that flooding and shading both modulated the outcome of AMF symbiosis for rice plants, partially by influencing the mycorrhizal P benefit. This finding has important implications for AMF application in rice production.

Ferritinophagy-Mediated ROS Production Contributed to Proliferation Inhibition, Apoptosis, and Ferroptosis Induction in Action of Mechanism of 2-Pyridylhydrazone Dithiocarbamate Acetate.

Reactive oxygen species (ROS) production is involved in the mechanism of action of a number of drugs, but the biological effects of ROS remain to be clarified. Furthermore, ferroptosis involves iron-dependent ROS production that may be derived from ferritinophagy; however, the association between ferroptosis and ferritinophagy has not been fully established. The present study demonstrated that dithiocarbamate derivatives (iron chelators) exhibited antineoplastic properties involving ferritinophagy induction, but whether the underlying mechanisms involved ferroptosis was unknown. To gain insight into the underlying mechanism, a dithiocarbamate derivative, 2-pyridylhydrazone dithiocarbamate s-acetic acid (PdtaA), was prepared. An MTT assay demonstrated that PdtaA inhibited proliferation involving ROS production (IC50 = 23.0 ± 1.5 µM for HepG2 cells). A preliminary mechanistic study revealed that PdtaA induced both apoptosis and cell cycle arrest. Notably, PdtaA also induced ferroptosis via downregulation of GPx4 and xCT, which was first reported for a dithiocarbamate derivative. Moreover, these cellular events were associated with ROS production. To explore the origin of ROS, expression of the ferritinophagy-related genes, ferritin, and nuclear receptor coactivator (NCOA4) were measured. Immunofluorescence and western blotting analysis indicated that PdtaA-induced ferritinophagy may contribute to ROS production. To investigate the role of ferritinophagy, autophagy inhibitor 3-methyladenin or genetic knockdown of NCOA4 was employed to inhibit ferritinophagy, which significantly neutralized the action of PdtaA in both apoptosis and ferroptosis. Taken together, PdtaA-induced cell cycle arrest, apoptosis, and ferroptosis were associated with ferritinophagy.

Gibberellin regulates UV-B-induced hypocotyl growth inhibition in Arabidopsis thaliana.

Plant response to light is a complex and diverse phenomenon. Several studies have elucidated the mechanisms via which light and hormones regulate hypocotyl growth. However, the hormone-dependent ultraviolet-B (UV-B) response in plants remains obscure. Involvement of gibberellins (GAs) in UV-B-induced hypocotyl inhibition and its mechanisms in Arabidopsis thaliana were investigated in the present research. UV-B exposure remarkably decreased the endogenous GA3 content through the UV RESISTANCE LOCUS 8 (UVR8) receptor pathway, and exogenous GA3 partially restored the hypocotyl growth. UV-B irradiation affected the expression levels of GA metabolism-related genes (GA20ox1, GA2ox1 and GA3ox1) in the hy5-215 mutant, resulting in increased GA content.ELONGATED HYPOCOTYL 5 (HY5) promoted the accumulation of DELLA proteins under UV-B radiation; HY5 appeared to regulate the abundance of DELLAs at the transcriptional level under UV-B. As a result, the GA3 content decreased, which eventually led to the shortening of the hypocotyl. To conclude, the present study provides new insight into the regulation of plant photomorphogenesis under UV-B.

Proton therapy for craniopharyngioma in adults: a protocol for systematic review and meta-analysis.

INTRODUCTION: Craniopharyngioma is the most challenging to treat brain tumour with high recurrence rates, which can be effectively reduced by adjuvant radiotherapy. In recent years, proton therapy (PT), with its physical properties of heavy ion beam, that is, Prague peak phenomenon, has been more frequently used in patients with craniopharyngioma. Compared with conventional X-ray beam radiotherapy, PT can reduce the damage to normal tissues and enlarge the damage to tumours. Some studies have shown that PT has advantages in the treatment of craniopharyngioma in adults. However, the optimal management of craniopharyngioma remains controversial. The purpose of this study was to evaluate the efficacy and safety of PT for craniopharyngioma in adults. METHODS AND ANALYSIS: We will search six databases (MEDLINE, EMBASE, Web of Science, the Cochrane Library, Amed, Scopus), clinical research registration websites and grey literature, aiming to identify randomised controlled trials (RCTs) on PT for craniopharyngioma in adults between 1 January 1954 and 28 September 2021. In the RCTs, PT will be used as the intervention group, and conventional X-ray beam radiotherapy will be used as the comparator group. Tumour recurrence and survival will be the primary outcome, and treatment-related toxicity will be the secondary outcome. The study selection, data extraction, bias risk and quality evaluation will be operated by two to four researchers independently. We will use Review Manager V.5.2 (RevMan V.5.2) for data analysis. If there is significant heterogeneity, we will identify the source of heterogeneity by subgroup analysis. ETHICS AND DISSEMINATION: Our study is based on existing RCTs and does not require ethical approval. The results of the study will be published in a peer-reviewed journal or at a related conference. PROSPERO REGISTRATION NUMBER: CRD42020200909.

Dose-Dependent Physiological and Transcriptomic Responses of Lettuce (Lactuca sativa L.) to Copper Oxide Nanoparticles-Insights into the Phytotoxicity Mechanisms.

Understanding the complex mechanisms involved in plant response to nanoparticles (NPs) is indispensable in assessing the environmental impact of nano-pollutants. Plant leaves can directly intercept or absorb NPs deposited on their surface; however, the toxicity mechanisms of NPs to plant leaves are unclear. In this study, lettuce leaves were exposed to copper oxide nanoparticles (CuO-NPs, 0, 100, and 1000 mg/L) for 15 days, then physiological tests and transcriptomic analyses were conducted to evaluate the negative impacts of CuO-NPs. Both physiological and transcriptomic results demonstrated that CuO-NPs adversely affected plant growth, photosynthesis, and enhanced reactive oxygen species (ROS) accumulation and antioxidant system activity. The comparative transcriptome analysis showed that 2270 and 4264 genes were differentially expressed upon exposure to 100 and 1000 mg/L CuO-NPs. Gene expression analysis suggested the ATP-binding cassette (ABC) transporter family, heavy metal-associated isoprenylated plant proteins (HIPPs), endocytosis, and other metal ion binding proteins or channels play significant roles in CuO-NP accumulation by plant leaves. Furthermore, the variation in antioxidant enzyme transcript levels (POD1, MDAR4, APX2, FSDs), flavonoid content, cell wall structure and components, and hormone (auxin) could be essential in regulating CuO-NPs-induced stress. These findings could help understand the toxicity mechanisms of metal NPs on crops, especially NPs resulting from foliar exposure.

Efficacy of stem cells therapy for Crohn's fistula: a meta-analysis and systematic review.

BACKGROUND: Fistulas have puzzled us all the time and stem cell therapy for it is still in its infancy. We conducted a meta-analysis and systematic review to evaluate the efficacy of stem cells and its potential mechanisms in the management of Crohn's fistula. METHODS: Electronic databases were searched comprehensively for studies reporting the efficacy and safety of stem cells in patients with any form of Crohn's fistula. A random-effects model was used, and all outcomes were calculated by SPSS 24.0. RESULTS: Twenty-nine articles with 1252 patients were included. It showed that stem cell group had a higher rate of fistula healing compared to placebo group in patients of Crohn's fistula (61.75% vs 40.46%, OR 2.21, 95% CI 1.19 to 4.11, P < 0.05). 3 × 107 cells/mL stem cell (SC) group had an advantage in fistula healing rate with 71.0% compared to other doses group of stem cells (RR 1.3, 95% CI 0.76 to 2.22). And the healing rates of patients with perianal and transsphincteric fistulas (77.95%, 76.41%) were higher than those with rectovaginal fistulas. It was an amazing phenomenon that CDAI and PDAI scores occurred an obviously transient rise with the use of stem cells after 1 month (both of P < 0.05), while they returned to the baseline level by giving stem cells 3 months later. Furthermore, the incidence rate of treatment-related adverse events in the stem cell group was significantly lower than in the placebo group (RR 0.58, 95% CI 0.30 to 1.14). CONCLUSIONS: Our study has highlighted that stem cells was a promising method in the treatment of Crohn's fistula based on its higher efficacy and lower incidence of adverse events, especially ADSCs and Cx601. While it also needs more clinical and pre-clinical studies to strengthen evidences in the future.

Foliar uptake, biotransformation, and impact of CuO nanoparticles in Lactuca sativa L. var. ramosa Hort.

Plant leaves can intercept and directly absorb nanoparticles (NPs) that deposit on their surface, which can lead severe phytotoxicity. However, there is a large blind spot when it comes to the fate and phytotoxicity of NPs after leaf exposure, even though foliar uptake is likely to occur. In this study, lettuce leaves (Lactuca sativa L. var. ramosa Hort.) were exposed to different concentrations of copper-oxide NPs (CuO-NPs, 0, 100, and 1000 mg L-1) for 5, 10, and 15 days. Foliar uptake, subcellular distribution, chemical forms, and impact of CuO-NPs on nutrient status, antioxidant systems, and lettuce growth were examined. Substantially elevated Cu levels were observed in lettuce leaves (up to 6350 mg kg-1), which was one magnitude greater than that in the roots (up to 525 mg kg-1). Cu translocation factors from leaves to roots ranged from 1.80 to 15.6%. The application of CuO-NPs severely inhibited lettuce growth and altered the nutrient status in plants (especially Mn, K, and Ca). Moreover, CuO-NPs increased H2O2 generation, malonaldehyde level (on the 5th and 10th day of exposure), and catalase activity (on the 15th day of exposure) in lettuce leaves. The Cu concentrations in subcellular fractions were ranked: cell wall ≈ organelles > soluble fraction in lettuce leaves, and organelles > cell wall > soluble fraction in lettuce roots. Undissolved Cu forms were predominant in lettuce, which may have helped to reduce the Cu's mobility and phytotoxicity in the plant. The findings of this study will be of great interest in areas with high levels of metal-NPs in the atmosphere.