CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.

JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex.

Whereas the actions of enhancers in gene transcriptional regulation are well established, roles of JmjC-domain-containing proteins in mediating enhancer activation remain poorly understood. Here, we report that recruitment of the JmjC-domain-containing protein 6 (JMJD6) to estrogen receptor alpha (ERα)-bound active enhancers is required for RNA polymerase II recruitment and enhancer RNA production on enhancers, resulting in transcriptional pause release of cognate estrogen target genes. JMJD6 is found to interact with MED12 in the mediator complex to regulate its recruitment. Unexpectedly, JMJD6 is necessary for MED12 to interact with CARM1, which methylates MED12 at multiple arginine sites and regulates its chromatin binding. Consistent with its role in transcriptional activation, JMJD6 is required for estrogen/ERα-induced breast cancer cell growth and tumorigenesis. Our data have uncovered a critical regulator of estrogen/ERα-induced enhancer coding gene activation and breast cancer cell potency, providing a potential therapeutic target of ER-positive breast cancers.

Individualized dynamic methylation-based analysis of cell-free DNA in postoperative monitoring of lung cancer.

BACKGROUND: The feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative monitoring remains unestablished. We aim to investigate the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients. METHODS: Matched tumor, tumor-adjacent tissues, and longitudinal blood samples from a cohort (MEDAL) were analyzed by ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort (n = 195) and validated in an independent cohort (DYNAMIC, n = 36). RESULTS: Tumor-informed methylation status enabled an accurate recurrence risk assessment better than the tumor-naïve methylation approach. Baseline timMRD-scores were positively correlated with tumor burden, invasiveness, and the existence and abundance of somatic mutations. Patients with higher timMRD-scores at postoperative time-points demonstrated significantly shorter disease-free survival in the MEDAL cohort (HR: 3.08, 95% CI: 1.48-6.42; P = 0.002) and the independent DYNAMIC cohort (HR: 2.80, 95% CI: 0.96-8.20; P = 0.041). Multivariable regression analysis identified postoperative timMRD-score as an independent prognostic factor for lung cancer. Compared to tumor-informed somatic mutation status, timMRD-scores yielded better performance in identifying the relapsed patients during postoperative follow-up, including subgroups with lower tumor burden like stage I, and was more accurate among relapsed patients with baseline ctDNA-negative status. Comparing to the average lead time of ctDNA mutation, timMRD-score yielded a negative predictive value of 97.2% at 120 days prior to relapse. CONCLUSIONS: The dynamic methylation-based analysis of peripheral blood provides a promising strategy for postoperative cancer surveillance. TRIAL REGISTRATION: This study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826). https://clinicaltrials.gov/ct2/show/NCT03634826 .

Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer.

BACKGROUND: Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC). METHODS: We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated. RESULTS: In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy. CONCLUSIONS: In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.

JMJD6 and U2AF65 co-regulate alternative splicing in both JMJD6 enzymatic activity dependent and independent manner.

JMJD6, a jumonji C (Jmj C) domain-containing protein demethylase and hydroxylase, has been implicated in an array of biological processes. It has been shown that JMJD6 interacts with and hydroxylates multiple serine/arginine-rich (SR) proteins and SR related proteins, including U2AF65, all of which are known to function in alternative splicing regulation. However, whether JMJD6 is widely involved in alternative splicing and the molecular mechanism underlying JMJD6-regulated alternative splicing have remained incompletely understood. Here, by using RASL-Seq, we investigated the functional impact of RNA-dependent interaction between JMJD6 and U2AF65, revealing that JMJD6 and U2AF65 co-regulated a large number of alternative splicing events. We further demonstrated the JMJD6 function in alternative splicing in jmjd6 knockout mice. Mechanistically, we showed that the enzymatic activity of JMJD6 was required for a subset of JMJD6-regulated splicing, and JMJD6-mediated lysine hydroxylation of U2AF65 could account for, at least partially, their co-regulated alternative splicing events, suggesting both JMJD6 enzymatic activity-dependent and independent control of alternative splicing. These findings reveal an intimate link between JMJD6 and U2AF65 in alternative splicing regulation, which has important implications in development and disease processes.

Arginine methylation of HSP70 regulates retinoid acid-mediated RARß2 gene activation.

Although "histone" methyltransferases and demethylases are well established to regulate transcriptional programs and to use nonhistone proteins as substrates, their possible roles in regulation of heat-shock proteins in the nucleus have not been investigated. Here, we report that a highly conserved arginine residue, R469, in HSP70 (heat-shock protein of 70 kDa) proteins, an evolutionarily conserved protein family of ATP-dependent molecular chaperone, was monomethylated (me1), at least partially, by coactivator-associated arginine methyltransferase 1/protein arginine methyltransferase 4 (CARM1/PRMT4) and demethylated by jumonji-domain-containing 6 (JMJD6), both in vitro and in cultured cells. Functional studies revealed that HSP70 could directly regulate retinoid acid (RA)-induced retinoid acid receptor ß2 (RARß2) gene transcription through its binding to chromatin, with R469me1 being essential in this process. HSP70's function in gene transcriptional regulation appears to be distinct from its protein chaperon activity. R469me1 was shown to mediate the interaction between HSP70 and TFIIH, which involves in RNA polymerase II phosphorylation and thus transcriptional initiation. Our findings expand the repertoire of nonhistone substrates targeted by PRMT4 and JMJD6, and reveal a new function of HSP70 proteins in gene transcription at the chromatin level aside from its classic role in protein folding and quality control.

CyHV-2 ORF104 activates the p38 MAPK pathway.

Cyprinid herpesvirus 2 (CyHV-2) is the pathogen responsible for herpesviral hematopoietic necrosis disease, which causes huge losses on aquaculture. So far the studies of CyHV-2 mainly focus on the identification and detection of this virus, but little is known about the role of specific CyHV-2 genes in the infection process. Based on the genomic information, CyHV-2 ORF104 encodes a kinase-like protein, which is highly conserved among the three CyHVs. Our study was initiated to investigate the role of kinase-like protein ORF104 during virus infection. Subcellular localization study showed that ORF104 was mainly expressed in the nucleus in both human HEK293T and fish EPC cells. However, deletion of the putative nuclear localization signal of ORF104 (ORF104M) resulted in the cytoplasmic distribution in HEK293T. We then examined whether MAPKs were involved in the ORF104-mediated signaling pathway by overexpressing ORF104 and ORF104M in HEK293T. Overexpression of ORF104 and ORF104M resulted in the up-regulation of p38 phosphorylation, but not JNK or ERK, indicating that ORF104 specifically activates p38 signaling pathway. In vivo study showed that CyHV-2 infection enhanced p38 phosphorylation in gibel carp (Carassius auratus gibelio). Interestingly, p38 inhibitor SB203580 strongly reduced fish death caused by CyHV-2 infection. Therefore, our study for the first time reveals the function of ORF104 during CyHV-2 infection, indicating that ORF104 is a potential vaccine candidate for CyHV-2.

An efficient and reliable geographic routing protocol based on partial network coding for underwater sensor networks.

Efficient routing protocols for data packet delivery are crucial to underwater sensor networks (UWSNs). However, communication in UWSNs is a challenging task because of the characteristics of the acoustic channel. Network coding is a promising technique for efficient data packet delivery thanks to the broadcast nature of acoustic channels and the relatively high computation capabilities of the sensor nodes. In this work, we present GPNC, a novel geographic routing protocol for UWSNs that incorporates partial network coding to encode data packets and uses sensor nodes' location information to greedily forward data packets to sink nodes. GPNC can effectively reduce network delays and retransmissions of redundant packets causing additional network energy consumption. Simulation results show that GPNC can significantly improve network throughput and packet delivery ratio, while reducing energy consumption and network latency when compared with other routing protocols.

Hamstring Strain Injury Risk Factors in Australian Football Change over the Course of the Season.

BACKGROUND/AIM: This study aimed to determine which factors were most predictive of hamstring strain injury (HSI) during different stages of the competition in professional Australian Football. METHODS: Across two competitive seasons, eccentric knee flexor strength and biceps femoris long head architecture of 311 Australian Football players (455 player seasons) were assessed at the start and end of preseason and in the middle of the competitive season. Details of any prospective HSI were collated by medical staff of participating teams. Multiple logistic regression models were built to identify important risk factors for HSI at the different time points across the season. RESULTS: There were 16, 33, and 21 new HSIs reported in preseason, early in-season, and late in-season, respectively, across two competitive seasons. Multivariate logistic regression and recursive feature selection revealed that risk factors were different for preseason, early in-season, and late in-season HSIs. A combination of previous HSI, age, height, and muscle thickness were most associated with preseason injuries (median area under the curve [AUC], 0.83). Pennation angle and fascicle length had the strongest association with early in-season injuries (median AUC, 0.86). None of the input variables were associated with late in-season injuries (median AUC, 0.46). The identification of early in-season HSI and late in-season HSI was not improved by the magnitude of change of data across preseason (median AUC, 0.67). CONCLUSIONS: Risk factors associated with prospective HSI were different across the season in Australian Rules Football, with nonmodifiable factors (previous HSI, age, and height) mostly associated with preseason injuries. Early in-season HSI were associated with modifiable factors, notably biceps femoris long head architectural measures. The prediction of in-season HSI was not improved by assessing the magnitude of change in data across preseason.

Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

Sulfite-Assisted Acetate Conversion from CO Electroreduction.

The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i. e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO3 2-) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO3 2- and oxygenated *C2 intermediates (i. e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at -0.6 A ⋅ cm-2, and extraordinary absolute value of peak partial current density as high as 1.52 A ⋅ cm-2 with adding SO3 2- in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.

Simultaneous quantification of 3',4'-dimethoxy flavonol-3-O-glucoside and its major metabolite in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study.

Hyperlipidemia is a disease characterized by abnormal blood lipid levels and is the leading risk factor for cardiovascular disease. 3',4'-Dimethoxy flavonol-3-O-glucoside (abbreviated DF3G) is a new lipid-lowering drug created as a flavonoid structural analog. The principal metabolite of DF3G in human plasma is the aglycone glucuronide conjugate M2. The purpose of this study is to use liquid chromatography-tandem mass spectrometry to develop and validate a quantitative analysis method for DF3G and its metabolite M2 in human plasma, and to use the method to investigate the pharmacokinetics of DF3G and M2 in a clinical trial. This method employed DF3G-d6 as the internal standard, and plasma samples were processed by protein precipitation. Isocratic separation could accurately differentiate DF3G, M2, and DF3G-d6 from endogenous components in the matrix or other components in the samples, and endogenous components in the matrix had little impact on ionization efficiency. Positive electrospray ionization with multiple reaction monitoring (MRM) transitions of m/z 461.2 → 299.0 for DF3G, m/z 475.1 → 299.1 for M2 and m/z 467.1 → 305.1 for DF3G-d6 was used for quantification. The DF3G and M2 linear range for plasma were in the range of 4.00/4.00 ng/mL to 4000/4000 ng/mL. Both the analytes and the internal standard were stable regardless of whether they were in solution or plasma samples. The accuracy of the average concentration of the quality control samples was within 15% of the theoretical value, and the RSD was less than 15%. The method is rapid, accurate, straightforward, and precise. It is appropriate for the determination of DF3G and M2 concentrations in human plasma and has been successfully applied to determine the pharmacokinetic analysis in phase I clinical trials.

Acidic CO2-to-HCOOH electrolysis with industrial-level current on phase engineered tin sulfide.

Acidic CO2-to-HCOOH electrolysis represents a sustainable route for value-added CO2 transformations. However, competing hydrogen evolution reaction (HER) in acid remains a great challenge for selective CO2-to-HCOOH production, especially in industrial-level current densities. Main group metal sulfides derived S-doped metals have demonstrated enhanced CO2-to-HCOOH selectivity in alkaline and neutral media by suppressing HER and tuning CO2 reduction intermediates. Yet stabilizing these derived sulfur dopants on metal surfaces at large reductive potentials for industrial-level HCOOH production is still challenging in acidic medium. Herein, we report a phase-engineered tin sulfide pre-catalyst (π-SnS) with uniform rhombic dodecahedron structure that can derive metallic Sn catalyst with stabilized sulfur dopants for selective acidic CO2-to-HCOOH electrolysis at industrial-level current densities. In situ characterizations and theoretical calculations reveal the π-SnS has stronger intrinsic Sn-S binding strength than the conventional phase, facilitating the stabilization of residual sulfur species in the Sn subsurface. These dopants effectively modulate the CO2RR intermediates coverage in acidic medium by enhancing *OCHO intermediate adsorption and weakening *H binding. As a result, the derived catalyst (Sn(S)-H) demonstrates significantly high Faradaic efficiency (92.15 %) and carbon efficiency (36.43 %) to HCOOH at industrial current densities (up to -1 A cm-2) in acidic medium.

Versatile Injectable Carboxymethyl Chitosan Hydrogel for Immediate Hemostasis, Robust Tissue Adhesion Barrier, and Antibacterial Applications.

Iatrogenic ulcers resulting from endoscopic submucosal dissection surgery remain a significant clinical concern due to the risk of uncontrolled bleeding. Herein, we have developed an injectable shear-thinning hydrogel cross-linked through electrostatic interactions and hydrogen bonding. The hydrogel underwent comprehensive characterization, focusing on rheological behavior, injectability, microstructure, film-forming capability, adhesion, swelling behavior, degradation kinetics, antibacterial efficacy, hemostatic performance, and biocompatibility. The incorporation of poly(vinyl alcohol) notably enhanced the internal structural stability and injection pressure, while the Laponite content influenced self-healing ability, modulus, and viscosity. Additionally, the hydrogel exhibited pH sensitivity, appropriate degradation, and swelling rates and displayed favorable film-forming and adhesion properties. Notably, it demonstrated excellent resistance against Escherichia coli and Staphylococcus aureus, highlighting its potential to create an optimal wound environment. In vivo studies further confirmed the hydrogel's exceptional hemostatic performance, positioning it as an optimal material for endoscopic submucosal dissection (ESD) surgery. Moreover, cell experiments and hemolysis tests revealed high biocompatibility, supporting their potential to facilitate the healing of iatrogenic ulcers post-ESD surgery. In conclusion, our hydrogels hold great promise as endoscopic treatment materials for ESD-induced ulcers given their outstanding properties.

Emerging materials and technologies for electrocatalytic seawater splitting.

The limited availability of freshwater in renewable energy-rich areas has led to the exploration of seawater electrolysis for green hydrogen production. However, the complex composition of seawater presents substantial challenges such as electrode corrosion and electrolyzer failure, calling into question the technological and economic feasibility of direct seawater splitting. Despite many efforts, a comprehensive overview and analysis of seawater electrolysis, including electrochemical fundamentals, materials, and technologies of recent breakthroughs, is still lacking. In this review, we systematically examine recent advances in electrocatalytic seawater splitting and critically evaluate the obstacles to optimizing water supply, materials, and devices for stable hydrogen production from seawater. We demonstrate that robust materials and innovative technologies, especially selective catalysts and high-performance devices, are critical for efficient seawater electrolysis. We then outline and discuss future directions that could advance the techno-economic feasibility of this emerging field, providing a roadmap toward the design and commercialization of materials that can enable efficient, cost-effective, and sustainable seawater electrolysis.

ER-localized JmjC domain-containing protein JMJD8 targets STING to promote immune evasion and tumor growth in breast cancer.

The STING-mediated type I interferon (IFN) signaling pathway has been shown to play critical roles in antitumor immunity. Here, we demonstrate that an endoplasmic reticulum (ER)-localized JmjC domain-containing protein, JMJD8, inhibits STING-induced type I IFN responses to promote immune evasion and breast tumorigenesis. Mechanistically, JMJD8 competes with TBK1 for binding with STING, blocking STING-TBK1 complex formation and restricting type I IFN and IFN-stimulated gene (ISG) expression as well as immune cell infiltration. JMJD8 knockdown improves the efficacy of chemotherapy and immune checkpoint therapy in treating both human and mouse breast cancer cell-derived implanted tumors. The clinical relevance is highlighted in that JMJD8 is highly expressed in human breast tumor samples, and its expression is inversely correlated with that of type I IFN and ISGs as well as immune cell infiltration. Overall, our study found that JMJD8 regulates type I IFN responses, and targeting JMJD8 triggers antitumor immunity.

Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer.

We report a personalized tumor-informed technology, Patient-specific pROgnostic and Potential tHErapeutic marker Tracking (PROPHET) using deep sequencing of 50 patient-specific variants to detect molecular residual disease (MRD) with a limit of detection of 0.004%. PROPHET and state-of-the-art fixed-panel assays were applied to 760 plasma samples from 181 prospectively enrolled early stage non-small cell lung cancer patients. PROPHET shows higher sensitivity of 45% at baseline with circulating tumor DNA (ctDNA). It outperforms fixed-panel assays in prognostic analysis and demonstrates a median lead-time of 299 days to radiologically confirmed recurrence. Personalized non-canonical variants account for 98.2% with prognostic effects similar to canonical variants. The proposed tumor-node-metastasis-blood (TNMB) classification surpasses TNM staging for prognostic prediction at the decision point of adjuvant treatment. PROPHET shows potential to evaluate the effect of adjuvant therapy and serve as an arbiter of the equivocal radiological diagnosis. These findings highlight the potential advantages of personalized cancer techniques in MRD detection.

SF3B1 mutation and ATM deletion codrive leukemogenesis via centromeric R-loop dysregulation.

RNA splicing factor SF3B1 is recurrently mutated in various cancers, particularly in hematologic malignancies. We previously reported that coexpression of Sf3b1 mutation and Atm deletion in B cells, but not either lesion alone, leads to the onset of chronic lymphocytic leukemia (CLL) with CLL cells harboring chromosome amplification. However, the exact role of Sf3b1 mutation and Atm deletion in chromosomal instability (CIN) remains unclear. Here, we demonstrated that SF3B1 mutation promotes centromeric R-loop (cen-R-loop) accumulation, leading to increased chromosome oscillation, impaired chromosome segregation, altered spindle architecture, and aneuploidy, which could be alleviated by removal of cen-R-loop and exaggerated by deletion of ATM. Aberrant splicing of key genes involved in R-loop processing underlay augmentation of cen-R-loop, as overexpression of the normal isoform, but not the altered form, mitigated mitotic stress in SF3B1-mutant cells. Our study identifies a critical role of splice variants in linking RNA splicing dysregulation and CIN and highlights cen-R-loop augmentation as a key mechanism for leukemogenesis.

Quantitative Analysis of Broken Rotor Bars in Cage Motor Based on Energy Characteristics of Vibration Signals.

The rotor, as the power output device of a cage motor, is subject to a type of invisible fault, BRB, during long-term use. The conventional motor vibration signal fault monitoring system only analyzes the rotor qualitatively for the fault of BRBs and cannot evaluate the fault degree of BRBs quantitatively. Moreover, the vibration signal used for monitoring has nonstationary and nonlinear characteristics. It is necessary to manually determine the time window and basis function when extracting the characteristics of the time-frequency domain. To address these problems, this paper proposes a method for quantitative analysis of BRBs based on CEEMD decomposition and weight transformation for feature extraction and then uses the AdaBoost to construct a classifier. The method applies CEEMD for adaptive decomposition while extracting IMFs' energy as the initial feature values, uses OOB for contribution evaluation of features to construct weight vectors, and performs a spatial transformation on the original feature values to expand the differences between the feature vectors. To verify the effectiveness and superiority of the method, vibration signals were collected from motors in four BRB states to produce rotor fault data sets in this paper. The experiment results show that the feature extraction method based on CEEMD decomposition and weight transformation can better extract the feature vectors from the vibration signals, and the constructed classifier can accurately perform quantitative analysis of BRB fault.