Genome folding principles uncovered in condensin-depleted mitotic chromosomes.

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1ß and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.

New plastids, old proteins: repeated endosymbiotic acquisitions in kareniacean dinoflagellates.

Dinoflagellates are a diverse group of ecologically significant micro-eukaryotes that can serve as a model system for plastid symbiogenesis due to their susceptibility to plastid loss and replacement via serial endosymbiosis. Kareniaceae harbor fucoxanthin-pigmented plastids instead of the ancestral peridinin-pigmented ones and support them with a diverse range of nucleus-encoded plastid-targeted proteins originating from the haptophyte endosymbiont, dinoflagellate host, and/or lateral gene transfers (LGT). Here, we present predicted plastid proteomes from seven distantly related kareniaceans in three genera (Karenia, Karlodinium, and Takayama) and analyze their evolutionary patterns using automated tree building and sorting. We project a relatively limited ( ~ 10%) haptophyte signal pointing towards a shared origin in the family Chrysochromulinaceae. Our data establish significant variations in the functional distributions of these signals, emphasizing the importance of micro-evolutionary processes in shaping the chimeric proteomes. Analysis of plastid genome sequences recontextualizes these results by a striking finding the extant kareniacean plastids are in fact not all of the same origin, as two of the studied species (Karlodinium armiger, Takayama helix) possess plastids from different haptophyte orders than the rest.

Genome folding principles revealed in condensin-depleted mitotic chromosomes.

During mitosis, condensin activity interferes with interphase chromatin structures. Here, we generated condensin-free mitotic chromosomes to investigate genome folding principles. Co-depletion of condensin I and II, but neither alone, triggered mitotic chromosome compartmentalization in ways that differ from interphase. Two distinct euchromatic compartments, indistinguishable in interphase, rapidly emerged upon condensin loss with different interaction preferences and dependence on H3K27ac. Constitutive heterochromatin gradually self-aggregated and co-compartmentalized with the facultative heterochromatin, contrasting with their separation during interphase. While topologically associating domains (TADs) and CTCF/cohesin mediated structural loops remained undetectable, cis-regulatory element contacts became apparent, providing an explanation for their quick re-establishment during mitotic exit. HP1 proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M- to G1-phase in the combined absence of HP1α, HP1ß and HP1γ, re-established constitutive heterochromatin compartments normally. In sum, "clean-slate" condensing-deficient mitotic chromosomes illuminate mechanisms of genome compartmentalization not revealed in interphase cells.

Machine Learning Assisted Wearable Wireless Device for Sleep Apnea Syndrome Diagnosis.

Sleep apnea syndrome (SAS) is a common but underdiagnosed health problem related to impaired quality of life and increased cardiovascular risk. In order to solve the problem of complicated and expensive operation procedures for clinical diagnosis of sleep apnea, here we propose a small and low-cost wearable apnea diagnostic system. The system uses a photoplethysmography (PPG) optical sensor to collect human pulse wave signals and blood oxygen saturation synchronously. Then multiscale entropy and random forest algorithms are used to process the PPG signal for analysis and diagnosis of sleep apnea. The SAS determination is based on the comprehensive diagnosis of the PPG signal and blood oxygen saturation signal, and the blood oxygen is used to exclude the error induced by non-pathological factors. The performance of the system is compared with the Compumedics Grael PSG (Polysomnography) sleep monitoring system. This simple diagnostic system provides a feasible technical solution for portable and low-cost screening and diagnosis of SAS patients with a high accuracy of over 85%.

Study of Temperature on the Corrosion Behavior of Antibacterial Steel by a Large-Scale Multiphase Flow Corrosion Test Loop.

The System #2 flow loop used in this study is a 4-inch-diameter, high-temperature, high-pressure system. In situ corrosion and electrochemical measurements were performed using a homemade flat corrosion specimen and a three-electrode probe. The experiment results show that temperature has an accelerated influence on the corrosion of antibacterial alloy steel. With the increase of temperature and the presence of O2 in the environment, a loose and porous corrosion product film was formed on the surface of the resistant steel, which made it easier for the corrosion medium to enter the corrosion product film from the pore, thus accelerating the corrosion.

Rapid construction of indole-fused 8-10 membered lactones via a tandem reaction.

An intramolecular anaerobic Mukaiyama hydration-initiated tandem reduction/condensation/acyl migration/aromatization reaction was developed, which enabled the rapid construction of indole-fused 8-10 membered lactones starting from cyclic 2-allyl-2-(2-nitrophenyl)-1,3-diketones. A nitro substituent in the substrates acted as both an oxygen source in the Mukaiyama hydration step and a nitrogen source in a tandem indole ring construction step. Our reaction features mild conditions, atom economy, and inexpensive reagents and it can be conveniently scaled up to a gram scale in modest yields. A rational reaction mechanism was also proposed based on previous reports and control experiments.

The Behavior of Supersonic Jets Generated by Combination Gas in the Steelmaking Process.

In the duplex steelmaking process, the oxygen flow rate is suppressed to reduce the increasing rate of the temperature in the molten bath, resulting in severe dynamic conditions. To improve the mixing effect of the molten bath, a Laval nozzle structure designed for combination gas has been proposed. In this research, five types of Laval nozzle structure have been built based on the combination gas content, and both numerical simulations and experiments are performed to analyze the flow field of the supersonic jet. The axial velocity and oxygen concentration were measured in the experiment, which agreed well with the numerically simulated data. The results show that both initial axial velocity and potential core length increase with the flow rate of combination gas. Further, applying a higher N2 flow rate could improve the oxygen utilization rate at different ambient temperatures, but this issue increases the oxygen utilization rate; however, the latter can be reduced at higher ambient temperatures.

Downregulation of lncRNA EPB41L4A-AS1 Mediates Activation of MYD88-Dependent NF-κB Pathway in Diabetes-Related Inflammation.

PURPOSE: Long non-coding RNAs (lncRNAs) have been shown to be involved in many human diseases. In this study, we aimed to reveal the role and molecular mechanism of lncRNA EPB41L4A-AS1 in type 2 diabetic mellitus (T2DM)-related inflammation. METHODS: To explore the relationships between the expression of EPB41L4A-AS1 and inflammatory factors in the blood of T2DM patients, we analyzed peripheral blood mononuclear cell (PBMC) expression microarrays of T2DM patients and expression microarrays of PBMC treated with lipopolysaccharide (LPS) from the GEO database. The relationship between EPB41L4A-AS1 and phospho-p65 was explored by Western blotting (WB) and immunofluorescence. The interactions between EPB41L4A-AS1 and myeloid differentiation factor 88 (MYD88) were also verified through quantitative real-time PCR, WB, and chromatin immunoprecipitation. Glycolysis and mitochondrial stress were detected by Seahorse. RESULTS: EPB41L4A-AS1 showed very low expression, which was significantly negatively correlated with levels of inflammatory factors in PBMCs of T2DM patients and PBMCs treated with LPS. These results were verified by cell experiments on PBMC and THP-1 cells. Knockdown of EPB41L4A-AS1 led to the phosphorylation and nuclear translocation of p65 and thus activated the NF-κB signaling pathway; it also reduced the enrichment of H3K9me3 in the MYD88 promoter and increased expression of MYD88. Overall, EPB41L4A-AS1 knockdown promoted the level of glycolysis and ultimately enhanced the inflammatory response. CONCLUSION: EPB41L4A-AS1 knockdown activated the NF-κB signaling pathway through a MYD88-dependent regulatory mechanism, promoted glycolysis, and ultimately enhanced the inflammatory response. These results demonstrate that EPB41L4A-AS1 is closely associated with inflammation in T2DM, and that low expression of EPB41L4A-AS1 may be used as an indicator of chronic inflammation and possible diabetic vascular complications in T2DM patients.

Effects of Multiple-Hole Baffle Arrangements on Flow Fields in a Five-Strand Asymmetric Tundish.

This paper reports on the re-engineering of standard five-strand tundish designs into a five-strand asymmetric tundish, which resulted in a non-uniform rate and bias for each strand. We sought to improve the casting conditions by optimizing the liquid steel flow-field in the tundish. Both a water modelling experiment and a numerical simulation were performed to analyze the flow-field according to various diversion hole diameters and injection angles. The results showed that the average residence time decreased as the diameter of the diversion holes increased. As the injection angle was increased, the average residence time initially decreased and then increased. The liquid steel from the ladle shroud rapidly extended to the #2 and #3 strands in the original tundish, which reduced the likelihood of inclusion collision and coalescence.

17-ß-Estradiol and Progesterone as Efficient Predictors of Survival in Older Women Undergoing Hip Fracture Surgery.

Objective: Sex hormones have been linked to fractures in older women. The purpose of this present study was to investigate the prognostic impact of preoperative sex hormone levels on 30-day mortality in older women undergoing hip fracture surgery. Patients and Methods: A total of 157 female subjects with hip fractures were eligible for the study conducted from January 2010 to December 2019. The serum levels of sex hormones [follicle-stimulating hormone, prolactin, progesterone, testosterone, luteinizing hormone, and 17-ß-estradiol (E2)] were measured at admission. To evaluate the prognostic significance of sex hormone levels, Cox proportional hazard models and Kaplan-Meier analyses were applied. Results: Of the 157 subjects, 13 (8.28%) deceased within 30 days. The deceased subjects had lower progesterone (P = 0.021) and E2 (P < 0.001) levels than the surviving group. Higher progesterone (HR = 0.168, 95% CI = 0.037-0.673) and E2 (HR = 0.857, 95% CI = 0.690-0.968) levels were the key protective factors for 30-day mortality in older women undergoing hip fracture surgery. Survival analysis showed that subjects with lower E2 or/and progesterone levels had a significantly higher percentage of 30-day mortality (log-rank test, P < 0.05). Conclusion: E2 and progesterone might be effective predictors of 30-day mortality in older women undergoing hip fracture surgery.

Effect of Lance Structure on Behavior of Coherent Jet in EAF Steelmaking Process.

During the electric arc furnace steelmaking process, the coherent jet technology was widely used to protect the kinetic energy of the supersonic oxygen jet and achieve better mixing effects. Comparing with the conventional oxygen lance, the coherent lance could increase the surface area of impaction cavity, resulting in a better stirring effect and higher reaction rate. However, there was limited research about the effect of restriction structure for the coherent lance tip on the flow field characteristic of the main oxygen jet. In this research, three kinds of restriction structures have been investigated by numerical simulation and combustion experiment at room and high ambient temperature conditions. Then an optimum restriction structure would be tested in a 75 t electrical arc furnace steelmaking process to verify its metallurgical property.

Upregulation of GPNCA is associated with poor prognosis through enhancement of tumor growth via regulating GSK3B.

GPNCA is a long non-coding RNA with unknown functions. In this study, using data from 9 cancers obtained from The Cancer Genome Atlas (TCGA), GPNCA was identified as overexpressed in cancer vs. normal tissues. The upregulation of GPNCA was associated with poor overall prognosis in colon, liver, renal clear cell and breast cancers. The upregulation of GPNCA was partly due to enhanced H3K27ac occupancy on its promoter region via EP300 and KAT2A/GCN5. The overexpression of GPNCA was positively related to tumor metastasis in colon cancer and poor disease-free and recurrence-free survival in colon and liver cancer. Both gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that GPNCA was closely linked to regulation of gene transcription and post-transcriptional modifications, which was further supported by in vitro cell cytoplasmic and nuclear RNA purification assessments. Furthermore, GPNCA was associated with cell growth. Our in vitro experiments demonstrated that GPNCA silencing inhibited tumor growth via inhibiting its nearby gene GSK3B. Taken together, these findings highlight GPNCA as a biomarker for cancer diagnosis and a potential target for future cancer drug development.

Convolutional neural network for cell classification using microscope images of intracellular actin networks.

Automated cell classification is an important yet a challenging computer vision task with significant benefits to biomedicine. In recent years, there have been several studies attempted to build an artificial intelligence-based cell classifier using label-free cellular images obtained from an optical microscope. Although these studies showed promising results, such classifiers were not able to reflect the biological diversity of different types of cell. While in terms of malignant cell, it is well-known that intracellular actin filaments are altered substantially. This is thought to be closely related to the abnormal growth features of tumor cells, their ability to invade surrounding tissues and also to metastasize. Therefore, being able to classify different types of cell based on their biological behaviors using automated technique is more advantageous. This article reveals the difference in the actin cytoskeleton structures between breast normal and cancer cells, which may provide new information regarding malignant changes and be used as additional diagnostic marker. Since the features cannot be well detected by human eyes, we proposed the application of convolutional neural network (CNN) in cell classification based on actin-labeled fluorescence microscopy images. The CNN was evaluated on a large number of actin-labeled fluorescence microscopy images of one human normal breast epithelial cell line and two types of human breast cancer cell line with different levels of aggressiveness. The study revealed that the CNN performed better in the cell classification task compared to a human expert.

LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2.

BACKGROUND: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and glutaminolysis in cancer cells. METHODS: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. FINDINGS: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. INTERPRETATION: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer.

Efficacy of K-wire tension band fixation compared with other alternatives for patella fractures: a meta-analysis.

BACKGROUND: To compare the efficacy and safety of K-wire tension band fixation (KTB) with other alternative approaches (cannulated screws, cable pin, and ring pin) for treatment of patella fractures by performing a meta-analysis. METHODS: PubMed and EMBASE databases were searched for all relevant studies. Standardized mean difference (SMD) or relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated for continuous or dichotomous outcomes via either a fixed- or random-effect model using Stata 13.0 software. RESULTS: Nine literatures involving 949 patients (581 in the KTB group and 368 in the control group) were included. Pooled analysis showed there were no differences in the success rate, operative time, healing time, and number of infections between patients undergoing KTB and others. However, the incidence of complications (RR = 8.04, 95% CI = 4.45-14.53; p < 0.001) and VAS (SMD = 0.642, 95% CI = 0.22-1.06; p = 0.003) were lower, while flexion degree (SMD = - 0.70 95% CI = - 1.04-- 0.36; p < 0.001), Böstman joint function score (SMD = - 0.68, 95% CI = - 1.10-- 0.27; p = 0.001), Iowa knee score (RR = 0.88, 95% CI = 0.81-0.96; p = 0.004), and Lysholm score (SMD = - 0.71, 95% CI = - 1.10-- 0.32; p < 0.001) were significantly higher in patients undergoing alternative approaches than the KTB. Subgroup analysis also demonstrated the cannulated screw fixation was superior to KTB in reducing the incidence of complications. CONCLUSIONS: Alternative treatments may be effective for management of patella fractures and should be attempted to be popularized in clinic.

Effect of shrouding CH4 flow rate on flow field and stirring ability of coherent jet in steelmaking process.

Characteristics of flow field and stirring ability of coherent jet with various shrouding CH4 flow rates on the molten bath were studied by combustion experiment and numerical simulation. The axial velocity and total temperature distributions of coherent jet under hot (1700 K) and cold (298 K) ambient condition were analyzed. The Eddy Dissipation Concept model was used in simulation with detail chemical kinetic mechanisms, and the numerical simulation results were agreed well with the combustion experiment in this research. Based on the simulation and experiment results, when the CH4 rate was 230, 207 and 184 Nm(3)/h, their disparity rate of average velocity and total temperature was small than 5 and 6 %, respectively, at high ambient temperature. Hence, the same stirring effect might be achieved by those three kinds of CH4 flow rates in EAF steelmaking process. According to the industrial application research, the best CH4 flow rate is 184 Nm(3)/h, which could stir molten bath well and reduce energy consumption in steelmaking process.

[Allografted olfactory mucosa gliacytes repair Wistar rats' sciatic nerve long defect].

OBJECTIVE: To investigate whether or not allografted olfactory mucosa gliacytes could repair peripheral nerve injure. METHODS: Olfactory mucosa gliacytes had been cultured in vitro for 2 weeks, then purified and condensed for later transplantation.Sixty adult female Wistar rats were randomized into 2 groups of 30 rats each, A (control) and B (test). Rats' left sciatic nerves were excised 25 mm long axons and retained epineurium lumen anastomosed to proximal ends. Culture mediums, and olfactory mucosa gliacytes were transplanted into epineurium lumen of A and B groups respectively. At 3 months postoperatively, the regenerations of injured sciatic nerves were evaluated by methods of macroscopy, photomicroscopy, transmission electron microscopy, retro-marked fluorescence red, the condensation of glial fibre acid protein (GFAP) and nerve growth factors (NF) assayed by immunofluorescence, and the concentration of myelin basic protein (MBP) and neurofilament protein (NF) assayed by enzyme linked immunosorbent assay. RESULTS: The regenerations of injured sciatic nerves were superior in B group to in A group; the transportation distance of retro-marked fluorescence red were longer in B group than in A group (P < 0.01). The condensations of GFAP and NGF were more dense in B group than in A group. The concentrations of MBP and NF were more high in B group than in A group (P < 0.01). The function scores of injured limbs were superior in B group to in A group (P < 0.01). The quantifications of nerve fibers and myelin fibers of injured sciatic nerve were larger in B group than in A group (P < 0.01). CONCLUSION: Allografted olfactory mucosa gliacytes could repair injured nerve defect.

[Comparison of competence of olfactory globular nerve layer gliocytes, olfactory epithelial gliacytes and SC in repairing nerve defect].

OBJECTIVE: To compare their competence of olfactory epithelial gliocytes, olfactory globular nerve layer (OGNL) gliocytes and SC in repair nerve defect of sciatic nerve, and select the best gliocytes for repair of peripheral nerve defect. METHODS: Olfactory epithelial gliocytes, OGNL gliocytes and SC were extracted from 20 female Wistar rats aged 2-3 months and cultured in vitro for 2 weeks, then purified and condensed for transplantation. Eighty adult female Wistar rats were randomized into groups A, B, C and D (n = 20). The left sciatic nerves were excised 25 mm axons and retained epineurium lumen anastomosed to proximal ends. The culture mediums, SC, OGNL gliocytes, and olfactory epithelial gliocytes were transplanted into the epineurium lumen of groups A, B, C and D, respectively. Three months postoperatively, the injured sciatic nerve regeneration was evaluated by methods of macroscopic observation, photomicroscope, transmission electron microscope, retro-marked fluorescence transportation distance, the glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were assayed by immunofluorescence, and the myelin basic protein (MBP) and neurofilament (NF) protein were assayed by ELISA. RESULTS: The scores of ankle joint were (3.325 +/- 0.963), (4.200 +/- 1.005), (5.143 +/- 0.635) and (5.950 +/- 0.154) in groups A, B, C and D, respectively; showing statistically significant difference between groups (P < 0.05). The observations of gross, sections under microscope and transmission electron microscope showed the regeneration of defect nerve was best in group D, followed by group C, and group B was superior to group A. The transportation distance of retro-marked fluorescence was longest in group D, followed by group C, and group B was superior to group A. The concentrations of GFAP and NGF were largest in group D, followed by group C, and group B was superior to group A. The MBP concentrations were (9.817 +/- 3.267), (12.347 +/- 3.091), (14.937 +/- 2.075) and (22.757 +/- 0.871) ng/mL in groups A, B, C and D, respectively; showing statistically significant difference between other groups (P < 0.05) except between group A and group B (P > 0.05). And the NF concentrations were (13.869 +/- 5.677), (18.498 +/- 3.889), (23.443 +/- 2.260) and (27.610 +/- 1.125) ng/mL in groups A, B, C and D, respectively; showing statistically significant difference between groups (P < 0.05). CONCLUSION: Olfactory epithelial gliocytes, OGNL gliocytes and SC transplantation could repair injured nerve. The competence of olfactory epitheliums is superior to the OGNL gliocytes and SC, and the OGNL gliocytes is better than SC.