Twist-Dependent Anisotropic Thermal Conductivity in Homogeneous MoS2_2 Stacks

Thermal transport property of homogeneous twisted molybdenum disulfide (MoS$_2$) is investigated using non-equilibrium molecular dynamics simulations with the state-of-art force fields. The simulation results demonstrate that the cross-plane thermal conductivity strongly depends on the interfacial twist angle, while it has only a minor effect on the in-plane thermal conductivity, exhibiting a highly anisotropic nature. A frequency-decomposed phonon analysis showed that both the cross-plane and in-plane thermal conductivity of MoS$_2$ are dominated by the low-frequency phonons below 15 THz. As the interfacial twist angle increases, these low-frequency phonons significantly attenuate the phonon transport across the interface, leading to impeded cross-plane thermal transport. However, the in-plane phonon transport is almost unaffected, which allows for maintaining high in-plane thermal conductivity. Additionally, our study revealed the strong size dependence for both cross-plane and in-plane thermal conductivities due to the low-frequency phonons of MoS$_2$. The maximum in-plane to cross-plane thermal anisotropy ratio is estimated as 400 for twisted MoS$_2$ from our simulation, which is in the same order of magnitude as recent experimental results (~900). Our study highlights the potential of twist engineering as a tool for tailoring the thermal transport properties of layered materials.Comment: 25 pages, 5 figures and with S

Temporal effects of tDCS on motor learning behavior

Transcranial direct current stimulation (tDCS) can improve motor learning. However, the effects of tDCS on the performance of a motor learning task, the choice reaction time task, remain elusive. Here, we examined the effects of tDCS on the learning and memory of a 4-choice visual-motor reaction time task (4-ChRT). Participants were randomly assigned to three tDCS groups: before (tDCSbefore), during (tDCSduring), or after (tDCSafter) motor practice, and two control groups, with (CONmp) and without (CON) motor practice. We studied the reaction time and error rate of the 4-ChRT task before (Pre), during, and 24 h (Post) after the motor practice and tDCS. We found that motor practice can improve motor learning and tDCS during motor practice can most effectively reduce reaction time and error rate. These results will shed light on future study of using non-invasive brain stimulation to improve motor function in patients with motor disorders

EGFR-targeted mAb therapy modulates autophagy in head and neck squamous cell carcinoma through NLRX1–TUFM protein complex

EGFR-targeted therapy in head and neck squamous cell carcinoma (HNSCC) patients frequently results in tumor resistance to treatment. Autophagy is an emerging underlying resistance mechanism, however, the molecular autophagy machinery in HNSCC cells and potential biomarkers of patient response to EGFR-targeted therapy remain insufficiently characterized. Here we show that the EGFR blocking with cetuximab leads to varied autophagic responses, which modulate cancer cell susceptibility to EGFR inhibition. Inhibition of autophagy sensitizes HNSCC cells to EGFR blockade. Importantly, we identify a novel signaling hub centering on the NLRX1-TUFM protein complex, promoting autophagic flux. Defects in the expression of either NLRX1 or TUFM result in compromised autophagy when treated with EGFR inhibitors. As a previously undefined autophagy-promoting mechanism, we found that TUFM serves as a novel anchorage site, recruiting Beclin-1 to mitochondria, promoting its polyubiquitination, and interfering with its interaction with Rubicon. This protein complex is also essential for endoplasmic reticulum (ER) stress signaling induction, possibly as an additional mechanism to promote autophagy. Utilizing tumor specimens from a novel neoadjuvant clinical trial, we show that increased expression of the autophagy adaptor protein, SQSTM1/p62, is associated with poor response to cetuximab therapy. These findings expand our understanding of the components involved in HNSCC autophagy machinery that responds to EGFR inhibitors, and suggest potential combinatorial approaches to enhance its therapeutic efficacy

1H NMR-based metabolomics of paired tissue, serum and urine samples reveals an optimized panel of biofluids metabolic biomarkers for esophageal cancer

IntroductionThe goal of this study was to establish an optimized metabolic panel by combining serum and urine biomarkers that could reflect the malignancy of cancer tissues to improve the non-invasive diagnosis of esophageal squamous cell cancer (ESCC).MethodsUrine and serum specimens representing the healthy and ESCC individuals, together with the paralleled ESCC cancer tissues and corresponding distant non-cancerous tissues were investigated in this study using the high-resolution 600 MHz 1H-NMR technique.ResultsWe identified distinct 1H NMR-based serum and urine metabolic signatures respectively, which were linked to the metabolic profiles of esophageal-cancerous tissues. Creatine and glycine in both serum and urine were selected as the optimal biofluids biomarker panel for ESCC detection, as they were the overlapping discriminative metabolites across serum, urine and cancer tissues in ESCC patients. Also, the were the major metabolites involved in the perturbation of “glycine, serine, and threonine metabolism”, the significant pathway alteration associated with ESCC progression. Then a visual predictive nomogram was constructed by combining creatine and glycine in both serum and urine, which exhibited superior diagnostic efficiency (with an AUC of 0.930) than any diagnostic model constructed by a single urine or serum metabolic biomarkers.DiscussionOverall, this study highlighted that NMR-based biofluids metabolomics fingerprinting, as a non-invasive predictor, has the potential utility for ESCC detection. Further studies based on a lager number size and in combination with other omics or molecular biological approaches are needed to validate the metabolic pathway disturbances in ESCC patients

Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells

Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 phosphorylation limited mitochondrial hyperfusion in glucose-starved breast cancer cells, as driven by downregulation of the mitofusin protein MFN2, leading to reduced oxidative phosphorylation and ROS production. In clinical specimens of breast cancer, reduced expression of MFN2 corresponded to poor prognosis in patients. In a mouse xenograft model of human breast cancer, there was an association in the core region of tumors between MFN2 downregulation and the presence of highly fragmented mitochondria. Collectively, our results suggest that KAP1 Ser473 phosphorylation acts through MFN2 reduction to restrict mitochondrial hyperfusion, thereby contributing to cancer cell survival under conditions of sustained metabolic stress

ODDFUZZ: Discovering Java Deserialization Vulnerabilities via Structure-Aware Directed Greybox Fuzzing

Java deserialization vulnerability is a severe threat in practice. Researchers have proposed static analysis solutions to locate candidate vulnerabilities and fuzzing solutions to generate proof-of-concept (PoC) serialized objects to trigger them. However, existing solutions have limited effectiveness and efficiency. In this paper, we propose a novel hybrid solution ODDFUZZ to efficiently discover Java deserialization vulnerabilities. First, ODDFUZZ performs lightweight static taint analysis to identify candidate gadget chains that may cause deserialization vulner-abilities. In this step, ODDFUZZ tries to locate all candidates and avoid false negatives. Then, ODDFUZZ performs directed greybox fuzzing (DGF) to explore those candidates and generate PoC testcases to mitigate false positives. Specifically, ODDFUZZ applies a structure-aware seed generation method to guarantee the validity of the testcases, and adopts a novel hybrid feedback and a step-forward strategy to guide the directed fuzzing. We implemented a prototype of ODDFUZZ and evaluated it on the popular Java deserialization repository ysoserial. Results show that, ODDFUZZ could discover 16 out of 34 known gadget chains, while two state-of-the-art baselines only identify three of them. In addition, we evaluated ODDFUZZ on real-world applications including Oracle WebLogic Server, Apache Dubbo, Sonatype Nexus, and protostuff, and found six previously unreported exploitable gadget chains with five CVEs assigned.Comment: To appear in the Main Track of IEEE S&P 202

Persistent surgical wound bleeding: A rare condition related to acquired hemophilia A

SummaryAcquired hemophilia A (AHA) is a rare condition that predisposes affected patients to a bleeding tendency, even after a trivial physical insult. We present our experience with a 45-year-old male patient who was referred to our institute because of persistent bleeding from a left forearm surgical wound after fasciotomy. He was diagnosed as having AHA. Surgical treatment in combination with recombinant activated factor VII (rFVIIa) led to a satisfactory result. Clinical awareness and multidisciplinary professional connections are necessary in the treatment of AHA. Acquired hemophilia should be considered in the differential diagnosis of patients with uncontrolled bleeding episodes

WashU Epigenome Browser update 2022

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called \u27Dynamic\u27 tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/