Pervasive Chromatin-RNA Binding Protein Interactions Enable RNA-Based Regulation of Transcription.

Increasing evidence suggests that transcriptional control and chromatin activities at large involve regulatory RNAs, which likely enlist specific RNA-binding proteins (RBPs). Although multiple RBPs have been implicated in transcription control, it has remained unclear how extensively RBPs directly act on chromatin. We embarked on a large-scale RBP ChIP-seq analysis, revealing widespread RBP presence in active chromatin regions in the human genome. Like transcription factors (TFs), RBPs also show strong preference for hotspots in the genome, particularly gene promoters, where their association is frequently linked to transcriptional output. Unsupervised clustering reveals extensive co-association between TFs and RBPs, as exemplified by YY1, a known RNA-dependent TF, and RBM25, an RBP involved in splicing regulation. Remarkably, RBM25 depletion attenuates all YY1-dependent activities, including chromatin binding, DNA looping, and transcription. We propose that various RBPs may enhance network interaction through harnessing regulatory RNAs to control transcription.

Maize smart-canopy architecture enhances yield at high densities.

Increasing planting density is a key strategy to enhance maize yields1-3. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis4-6, amongst other features. Here, we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant possessing upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and weakened shade-avoidance responses under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby attenuating RAVL1 activation of lac1 and reducing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate lac1 boosts maize yields under high densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize.

NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction.

The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export.

Development and validation of a prediction model for frailty in breast cancer patients with extended survival.

BACKGROUND: Breast cancer (BC) patients with extended survival show a higher incidence of frailty. This study aimed to develop and validate a novel model combining sociodemographic factors (SF) and disease-related factors (DRF) to identify frailty in BC patients with extended survival. METHODS: This cross-sectional study examined data from 1167 patients admitted to a large urban academic medical centre. Three types of predictive models were constructed in the training set (817 patients): the SF model, the DRF model, and the SF + DRF model (combined model). The model performance and effectiveness were assessed using receiver operating characteristic (ROC) curves, calibration plots and decision curves analysis (DCA). Then the model was subsequently validated on the validation set. RESULTS: The incidence of frailty in BC patients with extended survival was 35.8%. We identified six independent risk factors including age, health status, chemotherapy, endocrine therapy, number of comorbidities and oral medications. Ultimately, we constructed an optimal model (combined model C) for frailty. The predictive model showed significantly high discriminative accuracy in the training set AUC: 0.754, (95% CI, 0.719-0.789; sensitivity: 76.8%, specificity: 62.2%) and validation set AUC: 0.805, (95% CI, 0.76-0.85), sensitivity: 60.8%, specificity: 87.1%) respectively. A prediction nomogram was constructed for the training and validation sets. Calibration and DCA were performed, which indicated that the clinical model presented satisfactory calibration and clinical utility. Ultimately, we implemented the prediction model into a mobile-friendly web application that provides an accurate and individualized prediction for BC. CONCLUSIONS: The present study demonstrated that the prevalence of frailty in BC patients with extended survival was 35.8%. We developed a novel model for screening frailty, which may provide evidence for frailty screening and prevention.

Nitrogen-Neighbored Single-Cobalt Sites Enable Heterogeneous Oxidase-Type Catalysis.

The development of biomimetic catalytic systems that can imitate or even surpass natural enzymes remains an ongoing challenge, especially for bioinspired syntheses that can access non-natural reactions. Here, we show how an all-inorganic biomimetic system bearing robust nitrogen-neighbored single-cobalt site/pyridinic-N site (Co-N4/Py-N) pairs can act cooperatively as an oxidase mimic, which renders an engaged coupling of oxygen (O2) reduction with synthetically beneficial chemical transformations. By developing this broadly applicable platform, the scalable synthesis of greater than 100 industrially and pharmaceutically appealing O-silylated compounds including silanols, borasiloxanes, and silyl ethers via the unprecedented aerobic oxidation of hydrosilane under ambient conditions is demonstrated. Moreover, this heterogeneous oxidase mimic also offers the potential for expanding the catalytic scope of enzymatic synthesis. We anticipate that the strategy demonstrated here will pave a new avenue for understanding the underlying nature of redox enzymes and open up a new class of material systems for artificial biomimetics.

ALYREF links 3'-end processing to nuclear export of non-polyadenylated mRNAs.

The RNA-binding protein ALYREF plays key roles in nuclear export and also 3'-end processing of polyadenylated mRNAs, but whether such regulation also extends to non-polyadenylated RNAs is unknown. Replication-dependent (RD)-histone mRNAs are not polyadenylated, but instead end in a stem-loop (SL) structure. Here, we demonstrate that ALYREF prevalently binds a region next to the SL on RD-histone mRNAs. SL-binding protein (SLBP) directly interacts with ALYREF and promotes its recruitment. ALYREF promotes histone pre-mRNA 3'-end processing by facilitating U7-snRNP recruitment through physical interaction with the U7-snRNP-specific component Lsm11. Furthermore, ALYREF, together with other components of the TREX complex, enhances histone mRNA export. Moreover, we show that 3'-end processing promotes ALYREF recruitment and histone mRNA export. Together, our results point to an important role of ALYREF in coordinating 3'-end processing and nuclear export of non-polyadenylated mRNAs.

Transjugular liver biopsy: enlarge the indications for liver biopsy with reliable diagnostic quality.

BACKGROUND: Complications and diagnostic efficiency for liver biopsy are main concerns for clinicians. This study aimed to assess the safety and efficacy of transjugular liver biopsy (TJLB) compared with percutaneous liver biopsy (PLB) when patients had equal level of liver function and number of passes, using propensity score matching (PSM). METHODS: The clinical and pathological data of patients who received TJLB or PLB between January 2012 and October 2022 were collected. Matching factors included age, gender, cirrhosis, portal hypertension, liver function, creatinine, number of passes, hemodialysis, history of anti-coagulation and anti-platelet, and comorbidities. Coagulation indexes were not considered as matching factors due to different indications of the two techniques. RESULTS: 2711 PLBs and 30 TJLBs were evaluated. By PSM, 75 patients (50 PLBs, 25 TJLBs) were matched. The complication rates for TJLB and PLB were 4.0% (1/25) and 10.0% (5/50) (P > 0.05). Two PLBs had hepatic hemorrhage, one of which required only close monitoring (Grade 1) and the other needed hemostasis and rehydration therapy (Grade 2). The other 3 cases presented with mild abdominal pain (Grade 1). And only one TJLB presented with mild pain. The median number of complete portal tracts were 6.0 and 10.0 for TJLBs and PLBs (P < 0.05). Moreover, the median length of sample for TJLBs and PLBs were 10.0 and 16.5 mm (P < 0.05). The diagnostic efficiency of hepatopathy of unknown etiology of TJLB versus PLB groups before and after matching were 96.4% vs. 94.1% and 95.7% vs. 93.2%, respectively (P > 0.05). CONCLUSION: TJLB is an effective invasive diagnostic procedure that expands indications for liver biopsy with reliable diagnostic quality.

Evolution of the Electronic Structure of Ultrathin MnBi2Te4 Films.

Ultrathin films of intrinsic magnetic topological insulator MnBi2Te4 exhibit fascinating quantum properties such as the quantum anomalous Hall effect and the axion insulator state. In this work, we systematically investigate the evolution of the electronic structure of MnBi2Te4 thin films. With increasing film thickness, the electronic structure changes from an insulator type with a large energy gap to one with in-gap topological surface states, which is, however, still in drastic contrast to the bulk material. By surface doping of alkali-metal atoms, a Rashba split band gradually emerges and hybridizes with topological surface states, which not only reconciles the puzzling difference between the electronic structures of the bulk and thin-film MnBi2Te4 but also provides an interesting platform to establish Rashba ferromagnet that is attractive for (quantum) anomalous Hall effect. Our results provide important insights into the understanding and engineering of the intriguing quantum properties of MnBi2Te4 thin films.

[Explorations in and Practice of Integrating Ideological and Political Theories Education in Stomatology Textbooks].

Stomatology textbooks are an important carrier of integrated ideological and political education. The preparation of textbooks for the stomatology specialty in the new era is an important issue of concern for administrators and teachers of higher education institutions. Integrating ideological and political education in the instruction and practice composnents of academic courses on stomatology is an important issue to be resolved. Herein, we introduced the significance of ideological and political education and elaborated on the method of integrating ideological and political education in stomatology courses and textbooks from the perspectives of curriculum design, textbook compilation, teacher training, teaching evaluation, etc. We analyzed the different ways of integrating ideological and political education in stomatology courses and textbooks from the perspectives of classroom instruction, clinical practice, campus culture, social activities, and some other aspects.

Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

BACKGROUND: Aberrant cytokeratin 7 expression by hepatocytes (CK7+Hs) is the hallmark characteristic of cholestasis diseases, especially in ductopenia diseases such as primary biliary cholangitis (PBC). This study attempted to evaluate the differences and relationships between the clinical and histological features of aberrant cytokeratin 7 (CK7) expression by hepatocytes in PBC patients. METHODS: The clinicopathological data of patients diagnosed with PBC at the Second Hospital of Nanjing between January 2016 and September 2018 were analysed with SPSS 20.0. RESULTS: Eighty-nine PBC patients who underwent liver biopsy were enrolled in this study, and 15, 29 and 45 patients had aberrant CK7 expression by hepatocytes (CK7+Hs (2 +), CK7+Hs (1 +), and CK7-Hs, respectively). There were significant differences in TB, DB, ALP, TA, IgM, interface activity, and ductopenia grade between patients with CK7-Hs and CK7+Hs (2 +) (P < 0.05). The ductopenia grade was also significantly different between patients with CK7+Hs (2 +) and CK7+Hs (1 +) according to sex (P < 0.05). Upon merging the data of CK7+Hs (2 +) and CK7+Hs (1 +) into CK7+Hs, we found significant differences in AMA, AMA-M2, anti-gp210, TB, DB, ALP, TA, IgM, fibrosis, and ductopenia grade between CK7+Hs and CK7-Hs (P < 0.05). The odds ratios (ORs) (and 95% confidence intervals (CIs)) of CK7+Hs according to anti-gp210, ductopenia grade, and interface activity were 6.413 (95% CI 1.363-30.162), 4.145 (95% CI 1.898-9.052) and 3.247 (95% CI 1.556-6.775), respectively (P < 0.05). Spearman's rank correlation according to interface activity and ductopenia grade in patients with CK7+Hs (2 + , 1 + , 0) was r = 0.359 (P = 0.001) and r = 0.396 (P < 0.001), respectively. CONCLUSION: CK7+Hs serves as a cholestasis index of PBC and are associated with the ductopenia grade and interface activity. Aberrant cytokeratin 7 expression by hepatocytes can predict the ductopenia grade in primary biliary cholangitis.

A U2-snRNP-independent role of SF3b in promoting mRNA export.

To ensure efficient and accurate gene expression, pre-mRNA processing and mRNA export need to be balanced. However, how this balance is ensured remains largely unclear. Here, we found that SF3b, a component of U2 snRNP that participates in splicing and 3' processing of pre-mRNAs, interacts with the key mRNA export adaptor THO in vivo and in vitro. Depletion of SF3b reduces THO binding with the mRNA and causes nuclear mRNA retention. Consistently, introducing SF3b binding sites into the mRNA enhances THO recruitment and nuclear export in a dose-dependent manner. These data demonstrate a role of SF3b in promoting mRNA export. In support of this role, SF3b binds with mature mRNAs in the cells. Intriguingly, disruption of U2 snRNP by using a U2 antisense morpholino oligonucleotide does not inhibit, but promotes, the role of SF3b in mRNA export as a result of enhanced SF3b-THO interaction and THO recruitment to the mRNA. Together, our study uncovers a U2-snRNP-independent role of SF3b in mRNA export and suggests that SF3b contributes to balancing pre-mRNA processing and mRNA export.

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.

Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation.

Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1ß-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1ß stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1ß. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.

Fast and accurate autofocus control using Gaussian standard deviation and gradient-based binning.

We propose a fast and accurate autofocus algorithm using Gaussian standard deviation and gradient-based binning. Rather than iteratively searching for the optimal focus using an optimization process, the proposed algorithm directly calculates the mean of the Gaussian shaped focus measure (FM) curve to find the optimal focus location and uses the FM curve standard deviation to adapt the motion step size. The calculation only requires 3-4 defocused images to identify the center location of the FM curve. Furthermore, by assigning motion step sizes based on the FM curve standard deviation, the magnitude of the motion step is adaptively controlled according to the defocused measure, thus avoiding overshoot and unneeded image processing. Our experiment verified the proposed method is faster than the state-of-the-art Adaptive Hill-Climbing (AHC) and offers satisfactory accuracy as measured by root-mean-square error. The proposed method requires 80% fewer images for focusing compared to the AHC method. Moreover, due to this significant reduction in image processing, the proposed method reduces autofocus time to completion by 22% compared to the AHC method. Similar performance of the proposed method was observed in both well-lit and low-lighting conditions.

Unveiling the Unique Roles of Metal Coordination and Modulator in the Polymorphism Control of Metal-Organic Frameworks.

Polymorphism control of metal-organic frameworks is highly desired for elucidating structure-property relationships, but remains an empirical process and is usually done in a trial-and-error approach. We adopted the rarely used actinide cation Th4+ and a ditopic linker to construct a series of thorium-organic frameworks (TOFs) with a range of polymorphs. The extraordinary coordination versatility of Th4+ cations and clusters, coupled with synthetic modulation, gives five distinct phases, wherein the highest degree of interpenetration (threefold) and porosity (75.9 %) of TOFs have been achieved. Notably, the O atom on the capping site of the nine-coordinated Th4+ cation can function as a bridging unit to interconnect neighboring secondary building units (SBUs), affording topologies that are undocumented for other tetravalent-metal-containing MOFs. Furthermore, for the first time HCOOH has been demonstrated as a bridging unit of SBUs to further induce structural complexity. The resulting TOFs exhibit considerably different adsorption behaviors toward organic dyes, thus suggesting that TOFs represent an exceptional and promising platform for structure-property relationship study.

Paraliobacillus salinarum sp. nov., isolated from saline soil in Yingkou, China.

A novel Gram-stain-positive, facultatively aerobic, slightly halophilic, endospore-forming bacterium, designated G6-18T, was isolated from saline soil collected in Yingkou, Liaoning, PR China. Cells of strain G6-18T grew at 10-37 °C (optimum, 30 °C), at pH 6.0-9.0 (optimum, pH 8.0) and in the presence of 2-15 % (w/v) NaCl (optimum, 5 %). The strain could be clearly distinguished from the related species of the genus Paraliobacillus by its phylogenetic position and biochemical characteristics. It presented MK-7 as the major quinone and the dominant cellular fatty acids were iso-C16 : 0, anteiso-C15 : 0, C16 : 0 and iso-C14 : 0. The polar lipids consisted of diphosphatidylglycerol and phosphatidylglycerol as the major components. The G+C content of strain G6-18T genome was 35.3 mol%. 16S rRNA analysis showed that strain G6-18T had the highest similarity to Paraliobacillus ryukyuensis DSM 15140T, reaching 97.0 %, followed by Paraliobacillus quinghaiensis CGMCC 1.6333T with a value of 96.3 %. The average nucleotide identity values between strain G6-18T and Paraliobacillus ryukyuensis DSM 15140T, Paraliobacillus sedimins KCTC 33762T, Paraliobacillus quinghaiensis CGMCC 1.6333T and Paraliobacillus zengyii DSM 107811T were 74.3, 72.0, 73.2 and 72.8 %, respectively, and the digital DNA-DNA hybridization values between strain G6-18T and the neighbouring strains were 15.6, 13.8, 14.2 and 14.2 %, respectively. Based on phenotypic, chemotaxonomic and phylogenetic inferences, strain G6-18T represents a novel species of the genus Paraliobacillus, for which the name Paraliobacillus salinarum sp. nov. (=CGMCC 1.12058T=DSM 25428T) is proposed.

Coal and gangue identification method based on the intensity image of lidar and DenseNet.

Coal and gangue (rock) identification is the essential process in a coal preparation plant. In an actual coal preparation plant, the existing classification methods have many disadvantages in safety and identification rate. We utilized the echo intensity image (EII) of lidar for coal and gangue identification for the first time, to the best of our knowledge, and achieved outstanding recognition results with a convolutional neural network. First, we acquire the information of the 3D point cloud, including the distance and the echo intensity, and decompose them into two channels. Then, we utilize the distance channel to remove the background noises and separate the object and the echo intensity channel to construct the 2D EII. Finally, we prune the dense convolutional network (DenseNet-121) to DenseNet-40 for the real-time identification and compare its F1 score with the other two traditional recognition algorithms. The experiment shows that the F1 score of the DenseNet-40 is up to 0.96, which indicates the DenseNet-40 is provably higher than other traditional algorithms in accuracy. Through trial and error, we find that the echo intensity of lidar can clearly show the texture information of coal and gangue. After combining with the DenseNet-40, it has more benefits than the existing classification methods in accuracy, efficiency, and robustness.

Anti-TIF1 gamma-positive IPAF patient developed stage IVB lung squamous carcinoma in 1 year: a case report.

BACKGROUND: Patients with connective tissue disease, such as dermatomyositis (DM), and positive anti-TIF1γ self-antibodies are commonly diagnosed with malignant tumors as a comorbidity. The relationship between anti-TIF1γ self-antibodies and existing malignant tumors has been confirmed by several reports. However, interstitial pneumonia with autoimmune features (IPAF) cases with a positive anti-TIF1γ self-antibody developing to solid malignant tumors are rarely reported now. CASE PRESENTATION: Herein, we presented an IPAF patient with anti-TIF1γ self-antibodies. No evidence of malignant tumors was found at the initial visit. However, the patient had developed stage IVB lung squamous cell carcinoma at the 1-year follow-up review. CONCLUSIONS: Altogether, this report described a rare case of IPAF patient with anti-TIF1γ self-antibodies developed to advanced lung squamous cell carcinoma in 1 year. The present case highlights more frequent imaging examinations to identify the occurrence of malignant tumors as early as possible in IPAF patients with positive anti-TIF1γ self-antibodies.

The role of the XBP-1/AGR2 signaling pathway in the regulation of airway Mucin5ac hypersecretion under hypoxia.

Oversecretion of Mucin5ac (MUC5AC), which is primarily synthesized by goblet cells and is the major gel-forming mucin, is a hallmark of various pulmonary inflammatory diseases. Hypoxia is considered a common pathophysiologic feature in various pulmonary inflammatory diseases. It has been suggested that hypoxia-inducible factor 1α (HIF-1α) acts as a key factor in hypoxia-induced MUC5AC hypersecretion; however, the exact mechanisms that maintain the stability of HIF-1α and support oversecretion by airway epithelial cells under hypoxia are still unclear. With immunohistochemistry, we found overexpression of anterior gradient 2 (AGR2) in the bronchial epithelial cells of hypoxia-treated mice. With specific shRNA transduction, AGR2 was demonstrated to be a key factor in MUC5AC hypersecretion in vitro. Additionally, co-immunoprecipitation, cell immunochemistry and confocal microscopy experiments were performed to explore the interaction between HIF-1α and AGR2 during hypoxia-induced MUC5AC hypersecretion in vitro. The results indicated increased binding and intracytoplasmic colocation of HIF-1α and AGR2. Our findings suggest that AGR2 acts as a key regulator in hypoxia-induced airway MUC5AC hypersecretion by increasing the stability of HIF-1α. Additionally, the elevated expression of AGR2 induced by hypoxia in bronchial epithelial cells likely depends on an XBP-1-associated pathway.

Chemical Constituents from Sargassum fusiforme (Harv.) Setch.

Phytochemical investigation of Sargassum fusiforme (Harv.) Setch. led to the discovery of fifteen secondary metabolites, including three sterols, three monoterpenes, five nitrogenous compounds, two fatty acids, and two others. Among them, two compounds are new, while the other thirteen compounds were isolated from S. fusiforme for the first time. The structures of the two new compounds were identified by NMR and HR-ESI-MS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data.