Arabidopsis FLL2 promotes liquid-liquid phase separation of polyadenylation complexes.

An important component of cellular biochemistry is the concentration of proteins and nucleic acids in non-membranous compartments1,2. These biomolecular condensates are formed from processes that include liquid-liquid phase separation. The multivalent interactions necessary for liquid-liquid phase separation have been extensively studied in vitro1,3. However, the regulation of this process in vivo is poorly understood. Here we identify an in vivo regulator of liquid-liquid phase separation through a genetic screen targeting factors required for Arabidopsis RNA-binding protein FCA function. FCA contains prion-like domains that phase-separate in vitro, and exhibits behaviour in vivo that is consistent with phase separation. The mutant screen identified a functional requirement for FLL2, a coiled-coil protein, in the formation of FCA nuclear bodies. FCA reduces transcriptional read-through by promoting proximal polyadenylation at many sites in the Arabidopsis genome3,4. FLL2 was required to promote this proximal polyadenylation, but not the binding of FCA to target RNA. Ectopic expression of FLL2 increased the size and number of FCA nuclear bodies. Crosslinking with formaldehyde captured in vivo interactions between FLL2, FCA and the polymerase and nuclease modules of the RNA 3'-end processing machinery. These 3' RNA-processing components colocalized with FCA in the nuclear bodies in vivo, which indicates that FCA nuclear bodies compartmentalize 3'-end processing factors to enhance polyadenylation at specific sites. Our findings show that coiled-coil proteins can promote liquid-liquid phase separation, which expands our understanding of the principles that govern the in vivo dynamics of liquid-like bodies.

Efficacy of Noninvasive Brain Stimulation in Treating General Psychopathology Symptoms in Schizophrenia: A Meta-Analysis.

OBJECTIVES: Noninvasive brain stimulation (NIBS) has been shown to effectively alleviate negative and positive symptoms in patients with schizophrenia. However, its impact on depressive symptoms and general psychopathology symptoms (GPSs), which are crucial for functional outcomes, remains uncertain. We aimed to compare the efficacy of various NIBS interventions in treating depressive symptoms and GPSs. METHODS: We conducted a comprehensive search of multiple databases and performed a meta-analysis to evaluate the efficacy of NIBS in treating depressive symptoms and GPSs in schizophrenia. The effect sizes of NIBS for depression symptoms and GPSs were estimated using standard mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were employed to examine potential influencing factors on the pooled SMD of NIBS for GPSs. RESULTS: Our search yielded 35 randomized controlled trials involving 1715 individuals diagnosed with schizophrenia. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202320082). Neither repetitive transcranial magnetic stimulation (rTMS) nor transcranial direct current stimulation (tDCS) demonstrated significant improvements in depressive symptoms compared to sham controls. NIBS exhibited a small-to-moderate effect size for GPSs, with a pooled SMD of -0.2956 (95% CI: -0.459 to -0.132) and a heterogeneity (I2) of 58.9% (95% CI: 41.5% to 71.1%; p < 0.01) based on a random-effects model. Subgroup analyses of different types of NIBS, different frequencies of rTMS, and different stimulation sites of rTMS revealed no significant differences. Only sex had a significant influence on the effect size of NIBS for general psychopathology symptoms (p < 0.05). However, rTMS might be superior to tDCS, and high-frequency rTMS outperformed low-frequency rTMS in treating GPSs. CONCLUSIONS: We found a small-to-moderate effect size of NIBS in alleviating GPSs in patients with schizophrenia. Both rTMS and tDCS were more effective than sham stimulation in reducing GPSs in schizophrenia. The frequency used was associated with rTMS efficacy for GPSs.

Diagnosis of Clinically Significant Portal Hypertension Using CT- and MRI-based Vascular Model.

Background Currently, the hepatic venous pressure gradient (HVPG) remains the reference standard for diagnosis of clinically significant portal hypertension (CSPH) but is limited by its invasiveness and availability. Purpose To investigate a vascular geometric model for noninvasive diagnosis of CSPH (HVPG ≥10 mm Hg) in patients with liver cirrhosis for both contrast-enhanced CT and MRI. Materials and Methods In this retrospective study, consecutive patients with liver cirrhosis who underwent HVPG measurement from August 2016 to April 2019 were included. Patients without hepatic diseases were included and marked as non-CSPH to balance the ratio of CSPH 1:1. A variety of vascular parameters were extracted from the portal vein, hepatic vein, aorta, and inferior vena cava and then entered into a vascular geometric model for identification of CSPH. Diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC). Results The model was developed and tested with retrospective data from 250 patients with liver cirrhosis and 273 patients without clinical evidence of hepatic disease at contrast-enhanced CT examination, including 213 patients with CSPH (mean age, 49 years ± 12 [SD]; 138 women) and 310 patients without CSPH (mean age, 50 years ± 9; 177 women). For external validation, an MRI data set with 224 patients with cirrhosis (mean age, 49 years ± 10; 158 women) and a CT data set with 106 patients with cirrhosis (mean age, 53 years ± 12; 71 women) were analyzed. Significant reductions in mean whole-vessel volumes were observed in the portal vein (ranging from 36.9 cm3 ± 16.0 to 29.6 cm3 ± 11.1; P < .05) and hepatic vein (ranging from 35.3 cm3 ± 21.5 to 22.4 cm3 ± 15.7; P < .05) when CSPH occurred. Similarly, the mean whole-vessel lengths were shorter in patients with CSPH (portal vein: 1.7 m ± 1.2 vs 3.0 m ± 2.4, P < .05; hepatic vein: 0.9 m ± 1.5 vs 1.8 m ± 1.5, P < .05) than in those without CSPH. The proposed vascular model performed well in the internal test set (mean AUC, 0.90 ± 0.02) and external test sets (mean AUCs, 0.84 ± 0.12 and 0.87 ± 0.11). Conclusion A contrast-enhanced CT- and MRI-based vascular model was proposed with good diagnostic consistency for hepatic venous pressure gradient measurement. ClinicalTrials.gov registration nos. NCT03138915 and NCT03766880 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Roldán-Alzate and Reeder in this issue.

c-Jun-mediated JMJD6 restoration enhances resistance of liver cancer to radiotherapy through the IL-4-activated ERK pathway.

Radiotherapy is widely used in the treatment of liver cancer, but the efficacy can be limited by radioresistance. In this study, we attempt to delineate the possible molecular mechanism of c-Jun-regulated Jumonji domain-containing protein 6/interleukin 4/extracellular signal-regulated kinase (JMJD6/IL-4/ERK) axis in radioresistance of liver cancer. The expression of c-Jun was quantified in liver cancer tissues and cell lines, and the results indicated that c-Jun was upregulated in liver cancer tissues and cells. We further illustrated the role of c-Jun following gain- and loss-of-function strategies in malignant phenotypes of liver cancer cells. It was established that c-Jun elevated JMJD6 expression and augmented the malignancy and aggressiveness of liver cancer cells. The in vivo effects of c-Jun on radioresistance in liver cancer were validated in nude mice, in response to IL-4 knockdown or the ERK pathway inhibitor, PD98059. In the presence of JMJD6 upregulation, the expression of IL-4 was elevated in mice with liver cancer, which enhanced the radiation resistance. Moreover, knockdown of IL-4 inactivated the ERK pathway, thereby reversing the radiation resistance caused by overexpressed JMJD6 in tumor-bearing mice. Taken together, c-Jun augments the radiation resistance in liver cancer by activating the ERK pathway through JMJD6-upregulated IL-4 transcription.

Innovative angiography: a new approach to discover more hepatic vein collaterals in patients with cirrhotic portal hypertension.

BACKGROUND: The hemodynamics of patients with cirrhosis and portal hypertension are complex and variable. We aimed to investigate differences in venous pressures determined by innovative angiography and conventional angiography using balloon occlusion of the hepatic veins in patients with alcoholic cirrhosis and portal hypertension. METHODS: A total of 134 patients with alcoholic cirrhosis who fulfilled the inclusion criteria from June 2017 to June 2020 were included. During transjugular intrahepatic portosystemic shunt, conventional and innovative angiography were performed, and venous pressures were measured. A paired t-test and Pearson's correlation coefficient were used for analysis. RESULTS: Conventional and innovative hepatic angiography detected lateral branches of the hepatic vein in 26 (19.4%) and 65 (48.5%) cases, respectively (P < 0.001). Innovative angiography detected a total of 65 patients with lateral shunts, of whom 37 (56.9%) had initial shunts. The average wedged hepatic venous pressure and portal venous pressure of the initial lateral branches were 21.27 ± 6.66 and 35.84 ± 7.86 mmHg, respectively, with correlation and determination coefficients of 0.342 (P < 0.05) and 0.117, respectively. The mean hepatic venous pressure gradient and portal pressure gradient were 9.59 ± 7.64 and 26.86 ± 6.78 mmHg, respectively, with correlation and determination coefficients of 0.292 (P = 0.079) and 0.085, respectively. CONCLUSIONS: Innovative angiography reveals collateral branches of the hepatic veins more effectively than conventional angiography. Hepatic vein collateral branches are the primary factors leading to underestimation of wedged hepatic venous pressures and hepatic venous pressure gradients, with the initial hepatic vein collateral branches resulting in the most severe underestimations.

Correlation between hepatic venous pressure gradient and portal pressure gradient in patients with autoimmune cirrhotic portal hypertension and collateral branches of the hepatic vein.

AIM: To assess the correlation and agreement between hepatic venous pressure gradient (HVPG) and portal pressure gradient (PPG) in patients with autoimmune liver diseases (ALD) and portal hypertension, and to investigate the extent to which hepatic vein collateralization affects the accuracy of this assessment. METHODS: Ninety-eight patients with ALD between 2017 and 2021 who underwent transjugular intrahepatic portosystemic shunt with conventional and innovative 15 mL pressurized contrast were selected to measure wedged hepatic venous pressure (WHVP) and portal venous pressure and to calculate the HVPG and PPG. Pearson's correlation was used for correlation analysis between the two groups. Bland-Altman plots were plotted to estimate the agreement between paired pressures. RESULTS: The r values of PPG and HVPG in the early, middle, late, and portal venous visualization were 0.404, 0.789, 0.807, and 0.830, respectively, and the R2 values were 0.163, 0.622, 0.651, and 0.690, respectively. The p value for the r and R2 values in the early group was 0.015, and the p values in the remaining groups were less than 0.001. Bland-Altman plots showed that patients in the portal venous visualization group had the narrowest 95% limits of agreement. The mean value of the difference was close to the zero-scale line. CONCLUSIONS: In patients with ALD, the correlation between the HVPG and PPG was good, and the later the collateral development, the better the correlation. Hepatic vein collateral was an essential factor in underestimating WHVP and HVPG, and the earlier the collateral appeared, the more obvious the underestimation.

Neuron-Glial Antigen 2 Participates in Liver Fibrosis via Regulating the Differentiation of Bone Marrow Mesenchymal Stem Cell to Myofibroblast.

Neuron-glial antigen 2 (NG2, gene name: Cspg4) has been characterized as an important factor in many diseases. However, the pathophysiological relevance of NG2 in liver disease specifically regarding bone marrow mesenchymal stem cell (BMSC) differentiation to myofibroblast (MF) and the molecular details remain unknown. Human liver tissues were obtained from patients with different chronic liver diseases, and mouse liver injury models were induced by feeding a methionine-choline-deficient and high-fat diet, carbon tetrachloride administration, or bile duct ligation operation. NG2 expression was increased in human and mouse fibrotic liver and positively correlated with MF markers α-smooth muscle actin (αSMA) and other fibrotic markers in the liver. There was a co-localization between NG2 and αSMA, NG2 and EGFP (BMSC-derived MF) in the fibrotic liver determined by immunofluorescence analysis. In vitro, TGFß1-treated BMSC showed a progressive increase in NG2 levels, which were mainly expressed on the membrane surface. Interestingly, there was a translocation of NG2 from the cell membrane into cytoplasm after the transfection of Cspg4 siRNA in TGFß1-treated BMSC. siRNA-mediated inhibition of Cspg4 abrogated the TGFß1-induced BMSC differentiation to MF. Importantly, inhibition of NG2 in vivo significantly attenuated the extent of liver fibrosis in methionine-choline-deficient and high fat (MCDHF) mice, as demonstrated by the decreased mRNA expression of fibrotic parameters, collagen deposition, serum transaminase levels, liver steatosis and inflammation after the administration of Cspg4 siRNA in MCDHF mice. We identify the positive regulation of NG2 in BMSC differentiation to MF during liver fibrosis, which may provide a promising target for the treatment of liver disease.

Efficacy and safety of percutaneous cryoablation for elderly patients with small hepatocellular carcinoma: A prospective multicenter study.

BACKGROUND & AIMS: Management of elderly patients with hepatocellular carcinoma (HCC) has become a major concern. Some data suggest that cryoablation improves the outcomes of elderly patients with HCC, but its efficacy and safety remain unknown. This study aimed to evaluate and compare the efficacy and safety of percutaneous cryoablation with those of radiofrequency ablation (RFA) for elderly HCC patients. METHODS: In all, 223 patients with small HCC aged ≥70 years, treatment-naïve, without metastasis were enrolled and randomized into a cryoablation group (n = 112) or a RFA (n = 111) group from July 2015 to October 2018. The primary endpoint was local tumour progression (LTP) at 3 years after treatment. The secondary endpoints including overall survival (OS), tumour-free survival (TFS), LTP and safety were analysed for these two groups after both treatments. RESULTS: LTP rates at 1-, 3- and 5-year were 12%, 17% and 20% for cryoablation and 17%, 18% and 21% for RFA respectively (P = .735). For lesions >3 cm in diameter, LTP rates at 1- and 3-year were 13% and 22% in cryoablation group and 22% and 42% respectively, in the RFA group (P = .039). The 1-, 3- and 5-year OS rates were 90, 75% and 62% for cryoablation and 90%, 68% and 63% for RFA respectively (P = .331). The 1-, 3- and 5-year TFS rates were 59%, 32% and 25% in the cryoablation and 59%, 28% and 20% in the RFA respectively (P = .309). Major complications occurred in 6 patients (5%) following cryoablation and 6 patients (6%) following RFA (P = .886). CONCLUSION: Cryoablation and RFA had similar LTP in elderly patients with small HCC and this study failed to meet the primary endpoint, although for a relatively large early-stage HCC the LTP rate after cryoablation was significantly lower than that after RFA.

Functional consequences of splicing of the antisense transcript COOLAIR on FLC transcription.

Antisense transcription is widespread in many genomes; however, how much is functional is hotly debated. We are investigating functionality of a set of long noncoding antisense transcripts, collectively called COOLAIR, produced at Arabidopsis FLOWERING LOCUS C (FLC). COOLAIR initiates just downstream of the major sense transcript poly(A) site and terminates either early or extends into the FLC promoter region. We now show that splicing of COOLAIR is functionally important. This was revealed through analysis of a hypomorphic mutation in the core spliceosome component PRP8. The prp8 mutation perturbs a cotranscriptional feedback mechanism linking COOLAIR processing to FLC gene body histone demethylation and reduced FLC transcription. The importance of COOLAIR splicing in this repression mechanism was confirmed by disrupting COOLAIR production and mutating the COOLAIR proximal splice acceptor site. Our findings suggest that altered splicing of a long noncoding transcript can quantitatively modulate gene expression through cotranscriptional coupling mechanisms.

Neutrophil recruitment mediated by sphingosine 1-phosphate (S1P)/S1P receptors during chronic liver injury.

Excessive neutrophils are recruited to damaged tissue and cause collateral injury under chronic inflammatory conditions. Sphingosine 1-phosphate (S1P) modulates kinds of physiological and pathological actions by inducing recruitment of various cell types through S1P receptors (S1PRs). This study aimed to detect the S1P/S1PRs-mediated effects on neutrophil recruitment during chronic liver inflammation. In present study, increased neutrophils originated from bone marrow (BM) were detected in liver tissue of BDL-treated mice. Hepatic sphingosine kinase 1 (SphK, S1P rate-limiting enzyme) or S1P levels positively correlated with neutrophil marker expression in liver of mice and patients. In vitro, expression of S1PR1, S1PR2 and S1PR3 were detected in both mouse BM neutrophils and differentiated human neutrophil-like (dHL60) cells. S1P powerfully boosted the migration and cytoskeletal remodeling of BM neutrophils through S1PR1 or S1PR2. Different from BM neutrophils, the migration and cytoskeletal remodeling of dHL60 cells were mediated by S1PR2 or S1PR3. S1PR2 blockade obviously attenuates neutrophil infiltration in bile duct ligation (BDL)-induced mouse liver injury. In conclusion, S1P/S1PRs system plays a pivotal role in neutrophil recruitment.

Deep Convolutional Neural Network-Aided Detection of Portal Hypertension in Patients With Cirrhosis.

BACKGROUND & AIMS: Noninvasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. METHODS: We collected liver and spleen images from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient of 10 mm Hg or higher. In total, we analyzed 10,014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45,554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then sampled randomly and equiprobably for 6 times into training, validation, and test data sets (ratio, 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. RESULTS: The CT-based CNN analysis identified patients with CSPH with an area under the receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996-1.000), an AUC of 0.912 in the validation set (95% CI, 0.854-0.971), and an AUC of 0.933 (95% CI, 0.883-0.984) in the test data sets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999-1.000), an AUC of 0.924 in the validation set (95% CI, 0.833-1.000), and an AUC of 0.940 in the test data set (95% CI, 0.880-0.999). When the model development procedures were repeated 6 times, AUC values for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P > .05). CONCLUSIONS: We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a noninvasive and rapid method for detection of CSPH (ClincialTrials.gov numbers: NCT03138915 and NCT03766880).

Virtual Hepatic Venous Pressure Gradient with CT Angiography (CHESS 1601): A Prospective Multicenter Study for the Noninvasive Diagnosis of Portal Hypertension.

Purpose To develop and validate a computational model for estimating hepatic venous pressure gradient (HVPG) based on CT angiographic images, termed virtual HVPG, to enable the noninvasive diagnosis of portal hypertension in patients with cirrhosis. Materials and Methods In this prospective multicenter diagnostic trial (ClinicalTrials.gov identifier: NCT02842697), 102 consecutive eligible participants (mean age, 47 years [range, 21-75 years]; 68 men with a mean age of 44 years [range, 21-73 years] and 34 women with a mean age of 52 years [range, 24-75 years]) were recruited from three high-volume liver centers between August 2016 and April 2017. All participants with cirrhosis of various causes underwent transjugular HVPG measurement, Doppler US, and CT angiography. Virtual HVPG was developed with a three-dimensional reconstructed model and computational fluid dynamics. Results In the training cohort (n = 29), the area under the receiver operating characteristic curve (AUC) of virtual HVPG in the prediction of clinically significant portal hypertension (CSPH) was 0.83 (95% confidence interval [CI]: 0.58, 1.00). The diagnostic performance was prospectively confirmed in the validation cohort (n = 73), with an AUC of 0.89 (95% CI: 0.81, 0.96). Inter- and intraobserver agreement was 0.88 and 0.96, respectively, suggesting the good reproducibility of virtual HVPG measurements. There was good correlation between virtual HVPG and invasive HVPG (R = 0.61, P < .001), with a satisfactory performance to rule out (7.3 mm Hg) and rule in (13.0 mm Hg) CSPH. Conclusion The accuracy of a computational model of virtual hepatic venous pressure gradient (HVPG) shows significant correlation with invasive HVPG. The virtual HVPG also showed a good performance in the noninvasive diagnosis of clinically significant portal hypertension in cirrhosis. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Malayeri in this issue.

Quantitative regulation of FLC via coordinated transcriptional initiation and elongation.

The basis of quantitative regulation of gene expression is still poorly understood. In Arabidopsis thaliana, quantitative variation in expression of FLOWERING LOCUS C (FLC) influences the timing of flowering. In ambient temperatures, FLC expression is quantitatively modulated by a chromatin silencing mechanism involving alternative polyadenylation of antisense transcripts. Investigation of this mechanism unexpectedly showed that RNA polymerase II (Pol II) occupancy changes at FLC did not reflect RNA fold changes. Mathematical modeling of these transcriptional dynamics predicted a tight coordination of transcriptional initiation and elongation. This prediction was validated by detailed measurements of total and chromatin-bound FLC intronic RNA, a methodology appropriate for analyzing elongation rate changes in a range of organisms. Transcription initiation was found to vary ∼ 25-fold with elongation rate varying ∼ 8- to 12-fold. Premature sense transcript termination contributed very little to expression differences. This quantitative variation in transcription was coincident with variation in H3K36me3 and H3K4me2 over the FLC gene body. We propose different chromatin states coordinately influence transcriptional initiation and elongation rates and that this coordination is likely to be a general feature of quantitative gene regulation in a chromatin context.

Generation and characterization of a novel recombinant scFv antibody specific for Campylobacter jejuni.

Campylobacter jejuni is a leading cause of foodborne illness worldwide, mainly due to consumption and handling of contaminated raw chicken. Rapid detection methods for C. jejuni are vital for monitoring contamination levels in chicken products and reducing human Campylobacteriosis cases. The 'gold standard' culture-based method of Campylobacter detection takes 3-5 days and is too slow to permit effective intervention. Immuno-based methods are faster, but usually necessitate use of animals or hybridoma technology to produce antibodies; making them difficult and expensive to produce. Here, we report the generation and characterization of recombinant single-chain variable fragment (scFv) antibodies specific for C. jejuni cells, and evaluation of one scFv antibody for an immunomagnetic separation-quantitative PCR (IMS-qPCR) method to rapidly, sensitively, and specifically detect low numbers of C. jejuni. An scFv antibody phage-display library was constructed using spleen mRNA derived from a rabbit immunized with gamma-irradiated C. jejuni cells. This library was screened by surface biopanning against C. jejuni whole cells. Enriched clones were analyzed by enzyme-linked immunosorbent assay (ELISA). Two scFv antibodies that strongly and specifically recognized C. jejuni cell were expressed in Escherichia coli. Western blot analysis showed that one antibody, scFv80, was expressed as a soluble protein and retained its specific and strong binding to C. jejuni cells. This recombinant monoclonal scFv antibody was purified and used to covalently coat paramagnetic beads to be used for IMS-qPCR. The IMS-qPCR method was able to specifically and sensitively detect C. jejuni in mixed cultures within 3 h.

Seed Dormancy in Arabidopsis Is Controlled by Alternative Polyadenylation of DOG1.

DOG1 (Delay of Germination 1) is a key regulator of seed dormancy in Arabidopsis (Arabidopsis thaliana) and other plants. Interestingly, the C terminus of DOG1 is either absent or not conserved in many plant species. Here, we show that in Arabidopsis, DOG1 transcript is subject to alternative polyadenylation. In line with this, mutants in RNA 3' processing complex display weakened seed dormancy in parallel with defects in DOG1 proximal polyadenylation site selection, suggesting that the short DOG1 transcript is functional. This is corroborated by the finding that the proximally polyadenylated short DOG1 mRNA is translated in vivo and complements the dog1 mutant. In summary, our findings indicate that the short DOG1 protein isoform produced from the proximally polyadenylated DOG1 mRNA is a key player in the establishment of seed dormancy in Arabidopsis and characterizes a set of mutants in RNA 3' processing complex required for production of proximally polyadenylated functional DOG1 transcript.

Reactivity of a Base-Stabilized Germanium(I) Dimer toward Group 9 Metal(I) Chloride and Dimanganese Decacarbonyl.

The reactivity of the 2-imino-5,6-methylenedioxylphenylgermanium(I) dimer toward group 9 metal(I) chloride and dimanganese decacarbonyl is described. [LGe:]2 (1, L = 2-imino-5,6-methylenedioxylphenyl) underwent a disproportionation reaction with 1.5 equiv of group 9 metal(I) chloride [MCl(cod)]2 (M = Rh, Ir) in toluene to afford a mixture of the group 9 metallogermylene-chlorometal(I) complexes [LGeµ-{M(cod)}2Cl] (M = Rh (2), Ir (4)) and chlorogermylene-chlorometal(I) complexes [L(Cl)GeM(cod)Cl] (M = Rh (3), Ir (5)), respectively. The disproportionation property of 1 is further evidenced by its reaction with 0.5 equiv of Mn2(CO)10 in refluxing toluene to form a mixture of the manganogermylene dimer [(LGe)µ-{Mn(CO)4}]2 (7) and free ligand [LH] (8). Compounds 2-5, 7, and 8 were elucidated by NMR spectroscopy, X-ray crystallography, and DFT calculations, respectively.

[Research development of real-time functional magnetic resonance imaging neuro-feedback technology based on brain network connectivity].

The emergence of real-time functional magnetic resonance imaging (rt-fMRI) has provided foundations for neurofeedback based on brain hemodynamics and has given the new opportunity and challenge to cognitive neuroscience research. Along with the study of advanced brain neural mechanisms, the regulation goal of rt-fMRI neurofeedback develops from the early specific brain region activity to the brain network connectivity more accordant with the brain functional activities, and the study of the latter may be a trend in the area. Firstly, this paper introduces basic principle and development of rt-fMRI neurofeedback. Then, it specifically discusses the current research status of brain connectivity neurofeedback technology, including research approaches, experimental methods, conclusions, and so on. Finally, it discusses the problems in this field in the future development.

Cold-induced silencing by long antisense transcripts of an Arabidopsis Polycomb target.

Transcription in eukaryotic genomes generates an extensive array of non-protein-coding RNA, the functional significance of which is mostly unknown. We are investigating the link between non-coding RNA and chromatin regulation through analysis of FLC - a regulator of flowering time in Arabidopsis and a target of several chromatin pathways. Here we use an unbiased strategy to characterize non-coding transcripts of FLC and show that sense/antisense transcript levels correlate in a range of mutants and treatments, but change independently in cold-treated plants. Prolonged cold epigenetically silences FLC in a Polycomb-mediated process called vernalization. Our data indicate that upregulation of long non-coding antisense transcripts covering the entire FLC locus may be part of the cold-sensing mechanism. Induction of these antisense transcripts occurs earlier than, and is independent of, other vernalization markers and coincides with a reduction in sense transcription. We show that addition of the FLC antisense promoter sequences to a reporter gene is sufficient to confer cold-induced silencing of the reporter. Our data indicate that cold-induced FLC antisense transcripts have an early role in the epigenetic silencing of FLC, acting to silence FLC transcription transiently. Recruitment of the Polycomb machinery then confers the epigenetic memory. Antisense transcription events originating from 3' ends of genes might be a general mechanism to regulate the corresponding sense transcription in a condition/stage-dependent manner.

The relationship between self-stigma and quality of life in long-term hospitalized patients with schizophrenia: a cross-sectional study.

Objective: To investigate self-stigma's influence on schizophrenia patients' quality of life and its mediated impact by various factors. Methods: This study adopted a cross-sectional design and randomly selected 170 hospitalized patients with schizophrenia for evaluation. The assessment tools included the Positive and Negative Syndrome Scale (PANSS), Internalized Stigma of Mental Illness Scale (ISMI), Schizophrenia Quality of Life Scale (SQLS), and Coping Questionnaire for Schizophrenia Patients (CQSP), among others. Correlation analysis, regression analysis, and mediation analysis were used to test the correlation and mediation effects. Results: Self-stigma had a significant impact on quality of life (T = 8.13, p = 0.00). When self-stigma is used as a mediator, the problem-solving factor in coping strategies has an indirect effect on quality of life, which is significant (AB = -0.16, P = 0.02), while the avoidance factor in coping strategies has a direct effect on quality of life, which is significant (C' = 0.54, p < 0.001), and an indirect effect, which is also significant (AB = 0.25, p < 0.001). Conclusion: The study highlights the significant impact of self-stigma on the quality of life of schizophrenia patients, emphasizing the crucial roles of self-esteem and coping strategies. These findings suggest clinical interventions to improve quality of life should focus on reducing self-stigma, especially enhancing self-esteem and promoting adaptive coping strategies. By addressing these factors, we can better support the mental health and well-being of those with schizophrenia, offering an effective approach to rehabilitation.