PTBP1 as a potential regulator of disease.

Polypyrimidine tract-binding protein 1 (PTBP1) is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, which plays a key role in alternative splicing of precursor mRNA and RNA metabolism. PTBP1 is universally expressed in various tissues and binds to multiple downstream transcripts to interfere with physiological and pathological processes such as the tumor growth, body metabolism, cardiovascular homeostasis, and central nervous system damage, showing great prospects in many fields. The function of PTBP1 involves the regulation and interaction of various upstream molecules, including circular RNAs (circRNAs), microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). These regulatory systems are inseparable from the development and treatment of diseases. Here, we review the latest knowledge regarding the structure and molecular functions of PTBP1 and summarize its functions and mechanisms of PTBP1 in various diseases, including controversial studies. Furthermore, we recommend future studies on PTBP1 and discuss the prospects of targeting PTBP1 in new clinical therapeutic approaches.

Comparative study of the quick action effect of multiple enzyme-based nano-emulsified oils in enhancing nitrate contamination remediation in groundwater.

Emulsified vegetable oil (EVO), as a novel green slow-releasing substrate, has performed great potential in subsurface bioremediation due to its slow release and longevity. Nevertheless, the long time it takes to initiate this process still exposed some limitations. Herein, multiple enzyme-based EVOs (EN-EVOs) were developed to enhance the quick-acting effect in nitrate-contaminated bioremediation. This study demonstrated that EN-EVOs loaded with cellulose (c-EVO) and protein enzymes (p-EVO) performed best, not only did not change the advantages of traditional EVO, but also optimized the stability and particle size to the level of 0.8-0.9 and 247.95-252.25 nm, respectively. Nitrate (NO3-N) degradation further confirmed the superiority of c-EVO in rapidly initiating degradation and achieving stable denitrification. Compared with traditional EVO, the maximum start-up efficiency and the rapid achieving stable denitrification efficiency were improved by 37.6% and 1.71 times, respectively. In such situation, the corresponding NO3-N removal efficiency, kinetics rate constant (k1), and half-life period (t1/2) reached as high as 85.39%, as quick as 1.079 d-1, and as short as 0.64 d after 30-day cultivation. Meanwhile, the rapid conversion efficiency of NO2-N was observed (k2 = 0.083 d-1). High-throughput 16S rRNA gene sequencing indicated that the quick-acting process of NO3-N reduction coupled to c-EVO was mediated by microbial reducers (e.g., Ralstonia, Gulbenkiania, and Sphingobacterium) with regulations of narG, nirS and norB genes. Microorganisms with these genes could achieve quick-acting not only by enhancing microbial activity and the synthesis and metabolism of volatile fatty acids, but also by reducing the production and accumulation of loosely bound-extracellular polymeric substances (LB-EPS). These findings advance our understanding on fast-acting of NO3-N degradation supported by c-EVO and also offer a promising direction for groundwater remediation.

How to identify juxtaglomerular cell tumor by ultrasound: a case series and review of the literature.

PURPOSE: To study the value of ultrasound in the diagnosis of juxtaglomerular cell tumor (JGCT). METHODS: From January 2005 to July 2020, fifteen patients diagnosed as JGCT by surgical pathology in Peking Union Medical College Hospital were collected. All patients underwent preoperative ultrasound examination. The clinical, laboratory, ultrasound, computed tomography (CT), surgical, and pathological features of the patients were analyzed retrospectively. RESULTS: The 15 patients were 5 males and 10 females with a median age of 29 years (10∼72 years). 14 of them had hypertension and one had normal blood pressure. The tumors were all solitary, with a median diameter of 1.5 cm (0.9-5.9 cm). Among the fifteen patients, eleven were correctly detected by preoperative ultrasound, and four were missed. There was a significant difference in tumor size (2.64 ± 1.48 cm vs. 1.23 ± 0.21 cm) and whether the tumor protruded outward (9/11 vs. 0/4) between the ultrasound-detected group and the ultrasound-missed group (p = 0.010, p = 0.011). Of the 11 tumors detected by ultrasound, four were extremely hypoechoic, two were hypoechoic, three were isoechoic, and two were hyperechoic. Color Doppler showed no blood flow in five tumors with the size range from 0.9 to 2.0 cm, and mild blood flow in six tumors with the size range from 2.8 to 5.9 cm. CONCLUSIONS: JGCT is rare, and has characteristic clinical manifestations. Diagnosis should be suspected in case of secondary hypertension, particularly in young women, if no renal vascular cause was found. Ultrasound, combined with clinical manifestations, was helpful for the diagnosis.

Identification and expression of the CCO family during development, ripening and stress response in banana.

Plant hormone abscisic acid (ABA) plays an important role in plant growth, development and response to biotic / abiotic stressors. Thus, it is necessary to investigate the crucial genes associated with ABA synthesis. Currently, the carotenoid cleavage oxygenases (CCOs) family that function as the key step for ABA synthesis are not well understood in banana. In this study, 13 MaCCO genes and 12 MbCCO genes, divided into NCED subgroup and CCD subgroup, were identified from the banana genome, and their evolutionary relationship, protein motifs, and gene structures were also determined. Transcriptomic analysis suggested the involvement of CCO genes in banana development, ripening, and response to abiotic and biotic stressors, and homologous gene pairs showed homoeologue expression bias in the A or B subgenome. Our results identified MaNCED3A, MaCCD1, and MbNCED3B as the genes with the highest expression during fruit development and ripening. MaNCED5 / MbNCED5 and MaNCED9A might respond to abiotic stress, and MaNCED3A, 3B, 6 A, 9 A, and MbNCED9A showed transcriptional changes that could be a response to Foc4 infection. These findings may contribute to the characterization of key enzymes involved in ABA biosynthesis, as well as to identify potential targets for the genetic improvement of banana.

Lactate attenuates astrocytic inflammation by inhibiting ubiquitination and degradation of NDRG2 under oxygen-glucose deprivation conditions.

BACKGROUND: Brain lactate concentrations are enhanced in response to cerebral ischemia and promote the formation of reactive astrocytes, which are major components of the neuroinflammatory response and functional recovery, following cerebral ischemia. NDRG2 is upregulated during reactive astrocyte formation. However, its regulation and function are unclear. We studied the relationship between lactate and NDRG2 in astrocytes under conditions of ischemia or oxygen-glucose deprivation (OGD). METHODS: We examined astrocytic NDRG2 expression after middle cerebral artery occlusion (MCAO) using western blot and immunofluorescence staining. Under hypoxia conditions, we added exogenous L-lactate sodium (lactate) to cultured primary astrocytes to explore the effects of lactate on the ubiquitination modification of NDRG2. We profiled the transcriptomic features of NDRG2 silencing in astrocytes after 8 h of OGD conditions as well as exogenous lactate treatment by performing RNA-seq. Finally, we evaluated the molecular mechanisms of NDRG2 in regulating TNFα under OGD conditions using western blot and immunohistochemistry. RESULTS: Reactive astrocytes strongly expressed NDRG2 in a rat model of MCAO. We also showed that lactate stabilizes astrocytic NDRG2 by inhibiting its ubiquitination. NDRG2 inhibition in astrocytes increased inflammation and upregulated immune-associated genes and signaling pathways. NDRG2 knockdown induced TNFα expression and secretion via c-Jun phosphorylation. CONCLUSIONS: We revealed that under OGD conditions, lactate plays an important anti-inflammatory role and inhibits TNFα expression by stabilizing NDRG2, which is beneficial for neurological functional recovery. NDRG2 may be a new therapeutic target for cerebral ischemia.

Whole-cell tumor vaccines desialylated to uncover tumor antigenic Gal/GalNAc epitopes elicit anti-tumor immunity.

BACKGROUND: Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC). METHODS: Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αß T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs). RESULTS: Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αß T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice. CONCLUSION: Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.

Anti-L1 antibody-bound HPV16 pseudovirus is degraded intracellularly via TRIM21/proteasomal pathway.

BACKGROUND: Persistent HPV16 infection is the leading risk factor for developing cervical cancer. Anti-L1 antibodies against HPV16 produced in HPV16 infections play diverse roles in the clearance of virus infection and prevention of persistence. It has been implicated that the cervicovaginal squamous epithelial cells actually express TRIM21 and that some HPV16 particles could escape leaky endosomal compartment into the cytosol and that Fc receptor TRIM21 directly neutralize infection by targeting antibody-opsonized viruses for proteasomal degradation. We explored whether anti-L1 antibody opsonized HPV16 pseudovirus (PsV) entered into the cytosol could be neutralized by TRIM21-mediated activation of a proteasomal pathway to reduce the chance of persistent HPV16 infection. METHODS: HPV16 PsV were generated and extracted in HEK 293FT cells co-transfected with pcDNA3.1-eGFP and p16sheLL plasmids according to the standard protocol. The HPV16 PsV with capsid protein L1 was characterized by fluorescence microscopy and western blot, and the HPV16 PsV titer and anti-L1-bound PsV entry efficiency were detected by flow cytometry. The expressions of transcription factors (TF) and cytokines elicited by the TRIM21-activated proteasomal pathway were confirmed by dual-luciferase reporter assay and RT-qPCR. The changes in HPV16 PsV load with or without inhibitors in the infected HEK 293FT cells were determinated by qPCR. RESULTS: Simultaneous transfection with pcDNA3.1-eGFP and p16sheLL plasmids into the HEK 293FT cells resulted in the self-assembly of HPV16 PsV with capsid protein L1. Both HPV16 PsV and anti-L1-bound HPV16 PsV could infect HEK 293FT cells. Anti-L1-bound PsV up-regulated TRIM21 mediated-activation of proteasome and increased expressions of TF and cytokines in the infected cells where HPV16 PsV load reduced by ~ 1000-fold in the presence of anti-L1 antibody, but inhibition of proteasomal activity increased HPV16 PsV load. CONCLUSION: Our preliminary results indicate that anti-L1 antibody entered with HPV16 PsV into the cells could mediate degradation of HPV16 PsV by TRIM21-activated proteasomal pathway intracellularly, giving anti-capsid protein L1 antibody a role in host defense of persistent HPV16 infection.

Matrix stiffness regulates macrophage polarization in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease and the pathological basis of many fatal cardiovascular diseases. Macrophages, the main inflammatory cells in atherosclerotic plaque, have a paradox role in disease progression. In response to different microenvironments, macrophages mainly have two polarized directions: pro-inflammatory macrophages and anti-inflammatory macrophages. More and more evidence shows that macrophage is mechanosensitive and matrix stiffness regulate macrophage phenotypes in atherosclerosis. However, the molecular mechanism of matrix stiffness regulating macrophage polarization still lacks in-depth research, which hinders the development of new anti-atherosclerotic therapies. In this review, we discuss the important role of matrix stiffness in regulating macrophage polarization through mechanical signal transduction (Hippo, Piezo, cytoskeleton, and integrin) and epigenetic mechanisms (miRNA, DNA methylation, and histone). We hope to provide a new perspective for atherosclerosis therapy by targeting matrix stiffness and macrophage polarization.

SLC20A2-Associated Idiopathic basal ganglia calcification (Fahr disease): a case family report.

BACKGROUND: Idiopathic basal ganglia calcification (IBGC) is a genetic disorder of the nervous system commonly known as Fahr disease. IBGC patients with a genetic background are considered to have primary familial brain calcification (PFBC), also known as familial basal ganglia calcification (FBGC), or familial Fahr disease. It is a rare degenerative neurological disorder characterized by extensive bilateral basal ganglia calcification that can lead to a range of extrapyramidal symptoms and neuropsychiatric manifestations. Studies have suggested that more than 50 variants of SLC20A2 gene mutations account for approximately 50% of IBGC cases. There is a wide spectrum of mutation types, including frameshift, nonsense, and splice site mutations in addition to deletion and missense mutations. Here we report a case of familial basal ganglia calcification caused by a frameshift mutation in the SLC20A2 gene. We identified a heterozygous mutation in the SLC20A2 gene, c.1097delG (p.G366fs*89). To our knowledge, this mutation site has not been reported before. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with "unstable walking and involuntary movements between the eyes and eyebrows for 6 months". Based on the patient's family history, symmetrical calcification foci in the bilateral caudate nucleus head, thalamus, cerebellum and parietal lobe indicated by head CT, and gene test results, the diagnosis of familial Fahr disease caused by mutations in the SLC20A2 gene, c.1097delG p.G366fs*89) was confirmed. CONCLUSION: For the first time, we identified c.1097delG (p.G366fs*89) as a frameshift mutation in the IBGC family. This frameshift mutation caused the condition in this family of patients. This mutation not only broadens the range of known SLC20A2 mutations but also aids in the genetic diagnosis of IBGC.

IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells.

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.

COVID-19 Vaccine Rollouts and the Reproduction of Urban Spatial Inequality: Disparities Within Large US Cities in March and April 2021 by Racial/Ethnic and Socioeconomic Composition.

Rollouts of COVID-19 vaccines in the USA were opportunities to redress disparities that surfaced during the pandemic. Initial eligibility criteria, however, neglected geographic, racial/ethnic, and socioeconomic considerations. Marginalized populations may have faced barriers to then-scarce vaccines, reinforcing disparities. Inequalities may have subsided as eligibility expanded. Using spatial modeling, we investigate how strongly local vaccination levels were associated with socioeconomic and racial/ethnic composition as authorities first extended vaccine eligibility to all adults. We harmonize administrative, demographic, and geospatial data across postal codes in eight large US cities over 3 weeks in Spring 2021. We find that, although vaccines were free regardless of health insurance coverage, local vaccination levels in March and April were negatively associated with poverty, enrollment in means-tested public health insurance (e.g., Medicaid), and the uninsured population. By April, vaccination levels in Black and Hispanic communities were only beginning to reach those of Asian and White communities in March. Increases in vaccination were smaller in socioeconomically disadvantaged Black and Hispanic communities than in more affluent, Asian, and White communities. Our findings suggest vaccine rollouts contributed to cumulative disadvantage. Populations that were left most vulnerable to COVID-19 benefited least from early expansions in vaccine availability in large US cities.

Association of somatic mutations in BRCA2 BRC domain with chemotherapy sensitivity and survival in high grade serous ovarian cancer.

BACKGROUND: Mutations at sites crucial for the interaction between RAD51 and BRC domains impair the ability of BRCA2 homologous recombination. We aimed to clarify whether BRCA2 BRC domain-associated mutation correlates with sensibility of platinum-based chemotherapy and survival in high-grade serous ovarian cancer (HGSOC). METHODS: We identified BRCA2 BRC domain mutations by sequencing PCR-amplified amplicons of genomic DNA isolated from tumor tissues and peripheral blood leukocytes (PBL)in 113 patients with advanced EOC, and assessed platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). RESULTS: 21.23% (24 of 113) cases with somatic missense mutation but not germline mutation were identified. Among 24 cases with mutation, 33.3% (8 of 24) cases with nonsense mutation (C-terminal truncation) significantly prolonged median PFI (37 vs 8 months,P = 0.000), PFS (43 vs 14 months, p = 0.000) and OS (56 vs 31 months, P = 0.002); 66.7% (16 of 24) cases with missense mutation also prolonged median PFI (15 vs 8 months, P = 0.044), PFS (21 vs 14 months, P = 0.049) and OS (38 vs 31 months, P = 0.037), compared to those without any mutation. CONCLUSIONS: Somatic mutations in BRCA2 BRC domain confer a higher sensitivity to platinum-based therapy and are associated with a favourable survival in HGSOC.

Identification and expression of the BAHD family during development, ripening, and stress response in banana.

The BAHD family is involved in different biological roles in plants, including secondary metabolite synthesis, improving abiotic/biotic stress resistance, and influencing fruit quality. However, the knowledge about BAHD in banana, an important fruit crop, is limited. In this study, 46 banana BAHD genes (MaBAHDs) were identified and divided into four groups according to phylogenetic analysis. Most of the MaBAHD genes in the same group presented similar conserved motifs and genetic structures. MaBAHD genes have similar expression patterns in two banana varieties, and more genes showed high expressions in the roots. The comprehensive MaBAHD gene expression patterns obtained from two varieties of banana showed valuable information regarding their participation in fruit development, ripening, and response to abiotic/biotic stresses, suggesting that they play key roles in these processes. The systematic analysis of MaBAHD genes offered basic insight for further gene functional assays and potential applications in genetically improving banana cultivars.

Identification and Expression Analyses of the Special 14-3-3 Gene Family in Papaya and its Involvement in Fruit Development, Ripening, and Abiotic Stress Responses.

Plant 14-3-3 proteins play key roles in regulating growth, development, and stress responses. However, little is known about this gene family in papaya (Carica papaya L.). We characterized eight 14-3-3 genes from the papaya genome and designed them as CpGRF1-8. Based on phylogenetic, conserved motif, and gene structure analyses, papaya CpGRFs were divided into ε and non-ε groups. Expression analysis showed differential and class-specific transcription patterns in different organs. Quantitative real-time polymerase chain reaction analysis showed that most CpGRFs had large changes in expression during fruit development and ripening. This indicated that the CpGRFs were involved in regulating fruit development and ripening. Significant expression changes occurred after cold, salt, and drought treatments in papaya seedlings, indicating that CpGRFs were also involved in signaling responses to abiotic stress. These results provide a transcription profile of 14-3-3 genes in organs, during fruit development and ripening and in response to stress. Some highly expressed, fruit-specific, and stress-responsive candidate CpGRFs will be identified for further genetic improvement of papayas.

Analysis of the relationship between frailty index and 25(OH) vitamin D in elderly inpatients.

To analyze the relationship between frailty index and 25(OH) vitamin D in elderly inpatients. Totally 300 elderly patients in the geriatric department of Yuncheng Central Hospital from December 2019 to November 2020 were enrolled. There were 100 cases of non-frailty, pre-frailty, and frailty, respectively. The incidence of frailty was higher in patients with low household income, more diseases, less education, more medication, poor health self-assessment, and older age. There were statistical differences in vitamin D levels in weight loss, slower walking pace, reduced grip strength, decreased physical performance, and fatigue. There were significant differences in hypertension, diabetes mellitus, cerebral apoplexy, osteoporosis, and multiple chronic diseases among the three groups. The correlation analysis of senile frailty with age, weight, education level, income, BMI, combined chronic diseases, waist-to-hip ratio, weight loss, slower pace, decreased grip strength, decreased physical fitness, fatigue, and vitamin D level was statistically significant. Factors, included age, weight, education level, income, BMI, combined chronic diseases, waist-to-hip ratio, weight loss, slower pace, decreased grip strength, decreased physical fitness, fatigue, vitamin D level had a significant effect on frailty. Logistic regression analysis showed that vitamin D and age were independent influencing factors for frailty.

Ultrasound-Augmented Phase Transition Nanobubbles for Targeted Treatment of Paclitaxel-Resistant Cancer.

Paclitaxel (PTX) resistance in most epithelial ovarian cancers (EOCs) with increasing membrane expression of mucin 16 (MUC16) is mediated by the Toll-like receptor-myeloid differentiation factor 2/myeloid differentiation factor 88 (TLR4-MD2/MyD88) signaling pathway. 6-Shogaol (6S), an α,ß-unsaturated carbonyl compound with lipophilic property, can block PTX-induced formation of the TLR4-MD2 complex that activates the MyD88/NF-κB signaling pathway. Herein, to improve the effectiveness of 6S, augment the sensibility of PTX, and enhance the targeting ability of PTX-resistant cancer therapies, we report a class of 6S-loaded phase transition nanobubbles conjugated with the MUC16 antibody (6S@NBs-MUC16A), which can enhance the sensitivity of PTX to EOC cells through ultrasound-controlled targeted-delivery of 6S. The 6S@NB-MUC16A could enhance the targeting efficiency and organizational distribution of 6S in MyD88+ EOC area, and the 1 MHz ultrasound can be used as an initiator to trigger the "explosion" of nanobubbles and promote the 6S release. Furthermore, in vivo assessment results indicate that ultrasound-augmented 6S@NB-MUC16A can significantly improve the response of EOC to PTX and the inhibition ratio of tumor growth compared to the control-treated with PTX alone, and exhibit less toxicity to the critical organs. The ultrasound-augmented 6S@NB-MUC16A with less cytotoxicity could be a potentially useful nanosystem to surmount PTX resistance in EOC, which provides potential possibilities for the applications in the biological field.

Identification, Expression, and Interaction Network Analyses of the CDPK Gene Family Reveal Their Involvement in the Development, Ripening, and Abiotic Stress Response in Banana.

Calcium-dependent protein kinases (CDPKs) play vital roles in the regulation of plant growth, development, and tolerance to various abiotic stresses. However, little information is available for this gene family in banana. In this study, 44 CDPKs were identified in banana and were classified into four groups based on phylogenetic, gene structure, and conserved motif analyses. The majority of MaCDPKs generally exhibited similar expression patterns in the different tissues. Transcriptome analyses revealed that many CDPKs showed strong transcript accumulation at the early stages of fruit development and postharvest ripening in both varieties. Interaction network and co-expression analysis further identified some CDPKs-mediated network that was potentially active at the early stages of fruit development. Comparative expression analysis suggested that the high levels of CDPK expression in FJ might be related to its fast ripening characteristic. CDPK expression following the abiotic stress treatments indicated a significant transcriptional response to osmotic, cold, and salt treatment, as well as differential expression profiles, between BX and FJ. The findings of this study elucidate the transcriptional control of CDPKs in development, ripening, and the abiotic stress response in banana. Some tissue-specific, development/ripening-dependent, and abiotic stress-responsive candidate MaCDPK genes were identified for further genetic improvement of banana.

Protective effect of hawthorn extract against genotoxicity induced by benzo()pyrene in C57BL/6 mice.

Benzo()pyrene [B()P], widely originated from environmental pollution or food process such as roasting and frying, is a strong mutagen and potent carcinogen. Utilization of hawthorn has been reported against physical mutagens. Our study found that hawthorn extract (HE) contained abundant phenolic compounds, wherein chlorogenic acid was 2.78 mg/g, procyanidine B2 was 3.58 mg/g, epicatechin was 2.99 mg/g DW, which may contribute to anti-genotoxicity activity. So, the role of HE against B()P-induced genotoxicity in C57BL/6 mice was further assessed. Fifty mice were distributed into five groups: control group, B()P group (30 mg/kg, i.p.), B()P + HE-L group (100 mg/kg, i.g.), B()P + HE-M group (200 mg/kg, i.g.), B()P + HE-H group (400 mg/kg, i.g.). Mice were orally administered with solutions of HE for 10 days and injected intraperitoneally with B()P for 3 days from the 8th day. Results showed that B()P can induce significantly pathological damage in liver, lung and spleen, as well as decrease white blood cells (WBCs). Remarkably elevated levels of reactive oxygen species (ROS), DNA strand breaks (DSBs) and G1 cell cycle arrest were also found in B()P group, with upregulated expressions of p-H2AX, p-p53 and p21 in bone marrow cells. With administration of HE, liver, lung and spleen injury significantly mitigated, while WBCs were evidently increased in B()P-treated mice. Consistently, HE markedly reduced level of ROS, DSBs and G1 cell cycle arrest accompanied by reducing expressions of p-H2AX, p-p53 and p21 in bone marrow cells. Combined, these results indicated a protective role of HE on B()P-induced genotoxicity.

Graphene-oxide/TiO2 nanocomposite films with electron-donors for multicolor holography.

Graphene oxide (GO) with an ideal two-dimensional structure, presents outstanding optical, electric, and mechanical properties which draws great attention in advanced information devices. Recently, GO-based films were found to show photochromic behavior, especially for the TiO2 involved system which has potential data processing capability, such as storing holograms. However, expanding spectral response range and increasing exposure sensitivity are still challenges for such a film, due to the limited photo-quantum efficiency in reduction reaction. Here, an innovative method of "Immersion-Dropping" technology is proposed to fabricate GO-based continuous films. We, for the first time, achieve colored holography from violet to yellow regions on GO/TiO2 nanocomposite films with introduction of weak acid molecules. A "diffraction self-enhancement" is observed. The obtained results benefit from the broadband photo-response of weak acid molecules and photo-triggered transferring of electrons in multi-channels. This work provides a research strategy for the large-capacity information storage and colorful display device.

Label-Free Proteomic Analysis of Molecular Effects of 2-Methoxy-1,4-naphthoquinone on Penicillium italicum.

Penicillium italicum is the principal pathogen causing blue mold of citrus. Searching for novel antifungal agents is an important aspect of the post-harvest citrus industry because of the lack of higher effective and low toxic antifungal agents. Herein, the effects of 2-methoxy-1,4-naphthoquinone (MNQ) on P. italicum and its mechanism were carried out by a series of methods. MNQ had a significant anti-P. italicum effect with an MIC value of 5.0 µg/mL. The label-free protein profiling under different MNQ conditions identified a total of 3037 proteins in the control group and the treatment group. Among them, there were 129 differentially expressed proteins (DEPs, up-regulated > 2.0-fold or down-regulated < 0.5-fold, p < 0.05), 19 up-regulated proteins, 26 down-regulated proteins, and 67 proteins that were specific for the treatment group and another 17 proteins that were specific for the control group. Of these, 83 proteins were sub-categorized into 23 hierarchically-structured GO classifications. Most of the identified DEPs were involved in molecular function (47%), meanwhile 27% DEPs were involved in the cellular component and 26% DEPs were involved in the biological process. Twenty-eight proteins identified for differential metabolic pathways by KEGG were sub-categorized into 60 classifications. Functional characterization by GO and KEGG enrichment results suggests that the DEPs are mainly related to energy generation (mitochondrial carrier protein, glycoside hydrolase, acyl-CoA dehydrogenase, and ribulose-phosphate 3-epimerase), NADPH supply (enolase, pyruvate carboxylase), oxidative stress (catalase, glutathione synthetase), and pentose phosphate pathway (ribulose-phosphate 3-epimerase and xylulose 5-phosphate). Three of the down-regulated proteins selected randomly the nitro-reductase family protein, mono-oxygenase, and cytochrome P450 were verified using parallel reaction monitoring. These findings illustrated that MNQ may inhibit P. italicum by disrupting the metabolic processes, especially in energy metabolism and stimulus response that are both critical for the growth of the fungus. In conclusion, based on the molecular mechanisms, MNQ can be developed as a potential anti-fungi agent against P. italicum.