Predictive Impact of Prognostic Nutritional Index in Patients with Cancer Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

A few previous studies have investigated the prognostic value of the prognostic nutritional index (PNI) in patients treated with immune checkpoint inhibitors (ICIs); however, the results are inconsistent. Therefore, this study aimed to clarify the prognostic significance of PNI. The PubMed, Embase, and Cochrane Library databases were searched. A meta-analysis of the impact of PNI on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and rate of adverse events (AEs) in patients treated with ICIs was performed. Twenty-three studies involving 2,386 patients were included. Low PNI was associated with significantly poor OS (hazard ratio [HR] = 2.26, 95% confidence interval [CI]: 1.81-2.82, P < .001) and short PFS (HR = 1.75, 95% CI: 1.54-1.99, P < .001). Patients with low PNI tended to have a low ORR (odds ratio [OR] = 0.47, 95% CI: 0.34-0.65, P < .001) and DCR (OR = 0.43, 95% CI: 0.34-0.56, P < .001). However, the subgroup analysis demonstrated no significant association between PNI and survival time in patients receiving a programmed death ligand-1 inhibitor. PNI was significantly associated with survival time and treatment efficacy in patients treated with ICIs.

A four-enhancer RNA-based prognostic signature for thyroid cancer.

Enhancer RNAs (eRNAs) can serve as an independent prognostic factor for poor outcomes of cancer patients. The purpose of this study was to identify a vital eRNA signature that has prognostic value for thyroid cancer based on GTEx and TCGA screening. We downloaded gene expression data and clinical data of thyroid cancer included in the GTEx and TCGA databases and conducted data consolidation. eRNA expression data were extracted, and subjected to differential analysis and cluster analysis. Univariate Cox regression was used to screen the prognostic factors of thyroid cancer. Multivariate Cox regression was applied for prognostic risk assessment model construction, with the efficacy evaluated by receiver operating characteristic (ROC) curve. Downstream regulatory genes of candidate eRNAs were determined using correlation analysis. There were 79 differentially expressed eRNAs associated with thyroid cancer. These differentially expressed eRNAs could assign all thyroid cancer samples into three molecular subtypes, which showed a strong link to lymph node metastasis (N stage) of thyroid cancer patients. Additionally, four key eRNAs AC141930.1, NBDY, MEG3 and AP002358.1 closely related to the prognosis of thyroid cancer patients. The risk model based on the four eRNAs predicted the prognosis of thyroid cancer patients effectively. TPO, MGST2, THBS2 and SLC25A47P1 were potential downstream regulators of the four eRNAs involved in the development of thyroid cancer. Collectively, our data suggest that a four-eRNA signature consisting of AC141930.1, NBDY, MEG3 and AP002358.1 can accurately predict the prognosis of thyroid cancer patients.

The loss of Halloween gene function seriously affects the development and reproduction of Diaphorina citri (Hemiptera: Liviidae) and increases its susceptibility to pesticides.

The citrus industry has suffered severe losses as a result of Huanglongbing spread by Diaphorina citri. Controlling the population of D. citri is the key to preventing and controlling the spread of Huanglongbing. Ecdysteroids are key hormones that regulate insect development and reproduction. Therefore, the Halloween gene family involved in the ecdysone synthesis of D. citri is an ideal target for controlling the population growth of this insect. In this study, we successfully cloned four Halloween genes expressed during D. citri development. Silencing of one of the four genes resulted in a significant decrease in 20E titers in nymphs and significant decreases in the developmental, survival and emergence rates. Inhibiting Halloween gene expression in adults impeded the growth of the female ovary, diminished yolk formation, lowered vitellogenin transcription levels, and hence impaired female fecundity. This showed that Halloween genes were required for D. citri development and reproduction. DcCYP315A1 and DcCYP314A1 were highly expressed when D. citri was exposed to thiamethoxam and cypermethrin, and silencing these two genes made D. citri more sensitive to these two pesticides. Inhibition of DcCYP315A1 and DcCYP314A1 expression not only significantly delayed the development and reproduction of D. citri but also increased its susceptibility to pesticides. Therefore, these two genes are more suitable as potential target genes for controlling D. citri.

Investigation of the pump coupling efficiency of a side-pumping combiner based on tapered-fused method.

Side-pumping combiner is used for pumping double-clad fiber in various fiber laser schemes. However, its coupling efficiency and temperature characteristics suffer when pumped via a large numerical aperture (NA) pump light. We investigated the method of optimizing the coupling efficiency of a (2 + 1) ×1 combiner under a large NA pump light injection. After optimization of taper ratio and length of the pump fiber and fusion area between pump and signal fiber, the coupling efficiency increased and the temperature characteristic improved, which could be useful for fabrication of a side-pumping combiner for high-power fiber laser applications.

Association of Risk of Dementia With Direct Oral Anticoagulants Versus Warfarin Use in Patients With Non-valvular Atrial Fibrillation: A Systematic Review and Meta-analysis.

ABSTRACT: Atrial fibrillation (AF) is associated with an increased risk of dementia. Studies have shown the beneficial effects of anticoagulants in preventing dementia in this population. However, evidence around the use of direct oral anticoagulants (DOACs) versus warfarin in AF-related dementia prevention remains sparse. This systematic review and meta-analysis aimed to evaluate the use of DOACs versus warfarin in dementia prevention in this population. MEDLINE, EMBASE, PsycINFO, and the CENTRAL databases were systematically searched from its inception until May 2020. Nine studies (n = 611,069) were included for quantitative meta-analysis. DOACs use was associated with a lower risk of composite dementia outcomes compared with warfarin use [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.94, P = 0.03]. No significant difference was found in subtypes of dementia (vascular dementia, Alzheimer's disease, and cognitive disorder) between both groups. No significant difference in the risk of composite dementia outcomes between the dabigatran and warfarin groups (OR 0.97, 95% CI 0.88-1.08, P = 0.61). Apixaban (OR 0.58, 95% CI 0.50-0.67, P < 0.00001) and rivaroxaban (OR 0.67, 95% CI 0.61-0.75, P < 0.00001) use were both associated with a significantly lower risk of composite dementia outcomes compared with warfarin use. Findings need to be interpreted with caution because of low certainty of evidence. In conclusion, this systematic review and meta-analysis of 9 comparative studies demonstrated the superiority of DOACs over warfarin in prevention of dementia in AF. Future prospective trials with adequate follow-up period are warranted to ascertain its causal relationship.

The Interface between Nanoenergy and Self-Powered Electronics.

In recent decades, nanogenerators based on several techniques such as triboelectric effects, piezoelectric effects, or other mechanisms have experienced great developments. The nanoenergy generated by nanogenerators is supposed to be used to overcome the problem of energy supply problems for portable electronics and to be applied to self-powered microsystems including sensors, actuators, integrated circuits, power sources, and so on. Researchers made many attempts to achieve a good solution and have performed many explorations. Massive efforts have been devoted to developing self-powered electronics, such as self-powered communication devices, self-powered human-machine interfaces, and self-powered sensors. To take full advantage of nanoenergy, we need to review the existing applications, look for similarities and differences, and then explore the ways of achieving various self-powered systems with better performance. In this review, the methods of applying nanogenerators in specific circumstances are studied. The applications of nanogenerators are classified into two categories, direct utilization and indirect utilization, according to whether a treatment process is needed. We expect to offer a line of thought for future research on self-powered electronics.

[Research progress in original species identification in industry chain of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma is a kind of commonly used Chinese medicinal materials. Due to the overharvesting, the wild resource is endangering. Large market demand caused severely adulterant of commercial Rhei Radix et Rhizoma medicinal materials and decoction pieces. This manuscript reviewed the advances of the original species authentication in the industrial chain of Rhei Radix et Rhizoma during the latest decade, including characteristics and microscopic features, phytochemical analysis on anthraquinones, and molecular authentication based on DNA barcoding. Accordingly, an original species authentication route for the industrial chain of Rhei Radix et Rhizoma was summarized:(1)the identification of seeds and seedlings by DNA barcoding;(2) the selection of high variable sites based on the chloroplast genome;(3)biomonitoring of the Rhei Radix et Rhizoma medicinal materials and decoction pieces by two-dimensional DNA barcode;(4)traceability of Chinese patent medicines by third-generation sequencing. In conclusion, the combination of molecular identification and traditional identification methods provides a new idea for the identification of the original species of Rhei Radix et Rhizoma in the industrial chain and a essential guidance for the research of drug safety and efficacy of Rhei Radix et Rhizoma.

Induction of a Long Noncoding RNA Transcript, NR_045064, Promotes Defense Gene Transcription and Facilitates Intestinal Epithelial Cell Responses against Cryptosporidium Infection.

Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding RNA (lncRNA) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncRNA genes, including NR_045064, in infected cells is controlled by the NF-κB signaling. Functionally, inhibition of NR_045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR_045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR_045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR_045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR_045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncRNAs, such as NR_045064, play a role in regulating epithelial defense against microbial infection.

Artemyrianolides A-S, Cytotoxic Sesquiterpenoids from Artemisia myriantha.

Random screening suggested that the EtOH extract of Artemisia myriantha (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 µg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (1-19), involving 13 germacranolides (1-13), four guaianolides (14-17), and two eudesmanolides (18 and 19), together with 16 known sesquiterpenoids (20-35). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds 1, 2, and 11 were determined by X-ray crystallography. Structurally, compounds 2 and 11-13 maintain an uncommon cis-fused 10/5 bicyclic system and compound 12 possesses an unusual (7S) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound 9 showed cytotoxic activity on both HepG2 and Huh7 cells with IC50 values of 8.6 and 8.8 µM, and compounds 8 and 33 showed cytotoxicity to the three human hepatoma cell lines with IC50 values of 4.9 and 7.4 µM (HepG2), 4.3 and 7.8 µM (Huh7), and 3.1 and 9.8 µM (SMMC-7721), respectively.

Food Poisoning Caused by Deoxynivalenol at a School in Zhuhai, Guangdong, China, in 2019.

Deoxynivalenol (DON) or "vomitoxin" is a mycotoxin produced by Fusarium species. Few food poisoning cases caused by DON have been reported since the 1990s in China. However, on May 16, 2019, the Zhuhai Center for Disease Control and Prevention received a case report from primary school "S" that many students began vomiting after eating breakfast. To discern the cause and control the outbreak effectively, an epidemiological investigation was carried out. This retrospective cohort study defined both suspected and probable cases of food poisoning using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry to detect 16 mycotoxins simultaneously. A total of 101 cases (14 suspected and 87 probable) were identified, with an overall attack rate of 8.1%. All cases were in grades 1-3. The main symptoms of probable cases were vomiting (100%) and nausea (63%). The average incubation time was 25 min after eating. Comparison of students who ate breakfast provided by the school with those who did not revealed the relative risk was 6.0 (95% confidence intervals [CI] = 2.2-16) among students in grades 1-3. The concentration of DON in the leftover raw breakfast noodles ranged from 6856 to 11,982 µg/kg and 878.3 to 1074.2 µg/kg in leftover cooked noodles. DON exposure was 1.3-1.6 µg/kg body weight for grades 1-2 and 1.7-2.1 µg/kg body weight for grade 3. The attack rate of grade 3 was 4.3 times higher than that for grades 1-2 (95% CI = 3.0-6.3). The food poisoning outbreak on May 16, 2019 in primary school "S" in China, was determined to be caused by DON-contaminated commercial raw noodles.

Ultrasound findings of plasma leakage as imaging adjunct in clinical management of dengue fever without warning signs.

INTRODUCTION: Plasma leakage is a major cause of morbidity and mortality in dengue fever. Few studies have shown the sensitivity of thoracoabdominal ultrasound in detecting plasma leakage in severe dengue, however its sensitivity in the early presentation of dengue fever without warning signs remains unknown. This study is aimed to determine the role of serial ultrasound in order to detect plasma leakage in dengue fever without warning signs. METHODS: This prospective cohort study was conducted at Hospital Universiti Sains Malaysia (USM) from 1st October 2016 to 30th November 2017. Serial bedside ultrasound procedures were performed for 83 patients who were diagnosed as having dengue fever without warning signs and were initially treated as outpatients. Ultrasonography evidence of plasma leakage either pleural effusion, thickened gallbladder wall, ascites or pericardial effusion were compared with clinical findings and laboratory parameters for plasma leakage. RESULTS: Of the 83 dengue patients, eventually 72.3% had dengue fever with warning signs and 6.0% had severe dengue fever. There were 38 patients who had subclinical plasma leakage at initial presentation, 84.2% and 7.9% of them then progressed to dengue fever with warning signs and severe dengue respectively. There was a minimal agreement between serial bedside ultrasound and haematocrit level in the detection of plasma leakage (observed kappa 0.135). CONCLUSIONS: Serial bedside ultrasound is an adjunct procedure to physical examination and may detect plasma leakage earlier compared to haemoconcentration. The early usage of serial ultrasound is of paramount importance in detecting dengue patients who are at risk of progressing to severe dengue.

Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells following Cryptosporidium parvum Infection.

Cryptosporidium, a protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans and animals, is an important opportunistic pathogen in AIDS patients and one of the most common enteric pathogens affecting young children in developing regions. This parasite is referred to as a "minimally invasive" mucosal pathogen, and epithelial cells play a central role in activating and orchestrating host immune responses. We previously demonstrated that Cryptosporidium parvum infection stimulates host epithelial cells to release exosomes, and these released exosomes shuttle several antimicrobial peptides to carry out anti-C. parvum activity. In this study, we detected the upregulation of inflammatory genes in the liver and spleen following C. parvum intestinal infection in neonatal mice. Interestingly, exosomes released from intestinal epithelial cells following C. parvum infection could activate the nuclear factor kappa B signaling pathway and trigger inflammatory gene transcription in isolated primary splenocytes. Several epithelial cell-derived proteins and a subset of parasite RNAs were detected in the exosomes released from C. parvum-infected intestinal epithelial cells. Shuttling of these effector molecules, including the high mobility group box 1 protein, was involved in the induction of inflammatory responses in splenocytes induced by the exosomes released from infected cells. Our data indicate that exosomes released from intestinal epithelial cells upon C. parvum infection can activate immune cells by shuttling various effector molecules, a process that may be relevant to host systemic responses to Cryptosporidium infection.

Sodium butyrate ameliorates lipopolysaccharide-induced cow mammary epithelial cells from oxidative stress damage and apoptosis.

This study investigated the molecular mechanism by which sodium butyrate (NaB) causes oxidative stress damage induced by lipopolysaccharide (LPS) on cow mammary epithelial cells (MAC-T). We found that NaB significantly increased the activities of antioxidant enzymes, including superoxide dismutase, glutathione peroxidase, catalase, peroxidase, and total antioxidant capacity and decreased the reactive oxygen species production in LPS-induced MAC-T cells. NaB attenuated protein damage and reduced apoptosis in LPS-induced MAC-T cells. The messenger RNA (mRNA) levels of caspase-3, caspase-9, and Bax decreased, while the Bcl-2 mRNA level increased in LPS-induced MAC-T cells treated with NaB. Our results showed that NaB treatment increased the phosphoinositide 3-kinase (PI3K) and phospho-AKT (P-AKT) protein levels, whereas it decreased the Bax, caspase-3, and caspase-9 protein levels in LPS-induced MAC-T cells. However, the increase in PI3K and P-AKT protein levels and the decrease in Bax, caspase-3, and caspase-9 protein levels induced by NaB treatment were reversed when the cells were pretreated with LY294002 (PI3K inhibitor). These results indicate that NaB ameliorates LPS-induced oxidative damage by increasing antioxidative enzyme activities and ameliorating protein damage in MAC-T cells. In addition, NaB decreased apoptosis by inhibiting caspase-3, caspase-9, and Bax protein levels, and this action was mainly achieved via activation of the PI3K/AKT signaling pathways in LPS-induced MAC-T cells. These results provide substantial information for NaB as a chemical supplement to treat oxidative stress and its related diseases in ruminants.

EGFL6 promotes cell proliferation in colorectal cancer via regulation of the WNT/ß-catenin pathway.

Epidermal growth factor-like protein 6 (EGFL6) serves as an exocrine protein promoting proliferation and migration during carcinogenesis in ovarian cancer. However, its function and mechanisms in colorectal cancer (CRC) have not been completely explored. To investigate the role of EGFL6 in CRC cell growth, in vitro CCK8, colony formation assays, flow cytometric analysis of the cell cycle and apoptosis, and an in vivo tumor xenograft model were utilized. Additionally, Western blotting and luciferase reporter assays were used to investigate the underlying mechanisms of EGFL6 function on the WNT/ß-catenin signaling pathway. Immunohistochemical staining showed that EGFL6 is overexpressed in CRCs and this overexpression was highly correlated with advanced T classification, N classification, distant metastasis, and poor survival. Knocking down EGFL6 in CRC cell lines induced the inhibition of cell growth, cell cycle arrest at the G0/G1 phase, and apoptosis. Further, knockdown of EGFL6 blocked WNT/ß-catenin signaling as measured by Western blotting and luciferase reporter assay. Results also showed that recombinant EGFL6 (rEGFL6) induced ß-catenin in a concentration- and time-dependent manner. Further experiments showed that administration of rEGFL6 to cell cultures with EGFL6 knocked down or treated with the WNT/ß-catenin inhibitor ICG-001 increased ß-catenin and its downstream protein CyclinD1. The CCK8 assay showed that EGFL6 promoted CRC cell growth partly by the promotion of TCF7L2 expression. These findings suggest that EGFL6 plays a crucial role in the progression of CRC by regulation of the WNT/ß-catenin signaling pathway.

Hsp40 Protein DNAJB6 Interacts with Viral NS3 and Inhibits the Replication of the Japanese Encephalitis Virus.

The Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus prevalent in east and southeast Asia, the Western Pacific, and northern Australia. Since viruses are obligatory intracellular pathogens, the dynamic processes of viral entry, replication, and assembly are dependent on numerous host-pathogen interactions. Efforts to identify JEV-interacting host factors are ongoing because their identification and characterization remain incomplete. Three enzymatic activities of flavivirus non-structural protein 3 (NS3), including serine protease, RNA helicase, and triphosphatase, play major roles in the flaviviruses lifecycle. To identify cellular factors that interact with NS3, we screened a human brain cDNA library using a yeast two-hybrid assay, and identified eight proteins that putatively interact with NS3: COPS5, FBLN5, PPP2CB, CRBN, DNAJB6, UBE2N, ZNF350, and GPR137B. We demonstrated that the DnaJ heat shock protein family (Hsp40) member B6 (DNAJB6) colocalizes and interacts with NS3, and has a negative regulatory function in JEV replication. We also show that loss of DNAJB6 function results in significantly increased viral replication, but does not affect viral binding or internalization. Moreover, the time-course of DNAJB6 disruption during JEV infection varies in a viral load-dependent manner, suggesting that JEV targets this host chaperone protein for viral benefit. Deciphering the modes of NS3-interacting host proteins functions in virion production will shed light on JEV pathogenic mechanisms and may also reveal new avenues for antiviral therapeutics.

Attenuation of Intestinal Epithelial Cell Migration During Cryptosporidium parvum Infection Involves Parasite Cdg7_FLc_1030 RNA-Mediated Induction and Release of Dickkopf-1.

Intestinal infection by Cryptosporidium is known to cause epithelial cell migration disorder but the underlying mechanisms are unclear. Previous studies demonstrated that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using multiple models of intestinal cryptosporidiosis, we report here that C. parvum infection induces expression and release of the dickkopf protein 1 (Dkk1) from intestinal epithelial cells. Delivery of parasite Cdg7_FLc_1030 RNA to intestinal epithelial cells triggers transactivation of host Dkk1 gene during C. parvum infection. Release of Dkk1 is involved in C. parvum-induced inhibition of cell migration of epithelial cells, including noninfected bystander cells. Moreover, Dkk1-mediated suppression of host cell migration during C. parvum infection involves inhibition of Cdc42/Par6 signaling. Our data support the hypothesis that attenuation of intestinal epithelial cell migration during Cryptosporidium infection involves parasite Cdg7_FLc_1030 RNA-mediated induction and release of Dkk1 from infected cells.

Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA.

To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.

Planes of Reference for Orbital Fractures: A Technique for Reproducible Measurements of the Orbit on Computed Tomography Scans.

PURPOSE: Planes of reference for orbital fractures (PROF) was developed to standardize measurements made on orbital computed tomography scans. This study describes the use of PROF in determining the location along the orbital floor where the posterior ledge (PL) most commonly occurs. The transverse inclination and anterior-posterior inclination of the orbital floor will also be measured. METHODS: This study evaluates 104 patients with unilateral orbital fracture. Fifty-two patients had intact infra-orbital margin (IM) and 52 had fractured IM. Facial computed tomography scans were analyzed using Osirix Lite Digital Imaging and Communications in Medicine Viewer version 7.0.1 (Geneva, Switzerland). All skull positions were standardized by orientation according to Frankfurt and mid-sagittal planes. Measurements of distance of PL from IM were determined in the sagittal view. Measurements of the inclination of the orbital floor in the transverse and anterior-posterior sections were done on the coronal and sagittal views respectively. RESULTS: For patients with intact and fractured IM, the mean distances of PL from IM were 22.1 mm (95% CI: 21.2-23.0) and 21.1 mm (95% CI: 20.2-21.9) respectively. Mean transverse inclination was 19.4° (95% CI: 18.3-20.5). Mean anterior-posterior inclination was 15.5° (95% CI: 14.5-16.5). CONCLUSION: Planes of reference for orbital fractures is a simple and effective method to acquire standardized measurements of the orbital cavity on computed tomography scans. Understanding the commonest location of PL and the orientation of the orbital floor in 3-dimensional space allows surgeons to perform dissection with greater precision.

Involvement of Cryptosporidium parvum Cdg7_FLc_1000 RNA in the Attenuation of Intestinal Epithelial Cell Migration via Trans-Suppression of Host Cell SMPD3.

Intestinal infection by Cryptosporidium parvum causes inhibition of epithelial turnover, but underlying mechanisms are unclear. Previous studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected epithelial cells. Using in vitro and in vivo models of intestinal cryptosporidiosis, we report here that host delivery of parasite Cdg7_FLc_1000 RNA results in inhibition of epithelial cell migration through suppression of the gene encoding sphingomyelinase 3 (SMPD3). Delivery of Cdg7_FLc_1000 into infected cells promotes the histone methyltransferase G9a-mediated H3K9 methylation in the SMPD3 locus. The DNA-binding transcriptional repressor, PR domain zinc finger protein 1, is required for the assembly of Cdg7_FLc_1000 into the G9a complex and associated with the enrichment of H3K9 methylation at the gene locus. Pathologically, nuclear transfer of Cryptosporidium parvum Cdg7_FLc_1000 RNA is involved in the attenuation of intestinal epithelial cell migration via trans-suppression of host cell SMPD3.

LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications.

Long intergenic noncoding RNAs (lincRNAs) can regulate the transcription of inflammatory genes and thus may represent a new group of inflammatory mediators with a potential pathogenic role in inflammatory diseases. Here, our genome-wide transcriptomic data show that TNF-α stimulation caused up-regulation of 171 lincRNAs and down-regulation of 196 lincRNAs in murine intestinal epithelial cells in culture. One of the up-regulated lincRNAs, lincRNA-Cox2, is an early-responsive lincRNA induced by TNF-α through activation of the NF-ĸB signaling pathway. Knockdown of lincRNA-Cox2 resulted in reprogramming of the gene expression profile in intestinal epithelial cells in response to TNF-α stimulation. Specifically, lincRNA-Cox2 silencing significantly (P < 0.05) enhanced the transcription of Il12b, a secondary late-responsive gene induced by TNF-α. Mechanistically, lincRNA-Cox2 promoted the recruitment of the Mi-2/nucleosome remodeling and deacetylase (Mi-2/NuRD) repressor complex to the Il12b promoter region. Recruitment of the Mi-2/NuRD complex was associated with decreased H3K27 acetylation and increased H3K27 dimethylation at the Il12b promoter region, which might contribute to Il12b trans-suppression by lincRNA-Cox2. Thus, our data demonstrate a novel mechanism of epigenetic modulation by lincRNA-Cox2 on Il12b transcription, supporting an important role for lincRNAs in the regulation of intestinal epithelial inflammatory responses.