An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.

Controlled Self-Assembly, Isomerism, and Guest Uptake/Release of Charge-Reversible Lanthanide-Organic Octahedral Cages.

Charge plays a crucial role in the function of molecular and supramolecular systems, but coordination hosts capable of orthogonal charge regulation remain elusive so far. In this study, we report the condition-dependent self-assembly of charge-reversible lanthanide-organic tetra-capped octahedral cages, i.e., [Ln6(H3L)4]6+ and [Ln6L4]6-, from a series of lanthanide ions (Ln3+; Ln = Lu, Yb, Eu) and a tritopic tetradentate acylhydrazone ligand (H6L) featuring multiple deprotonation states and propeller conformations. While direct self-assembly under basic conditions produced a mixture of various ΔxΛ6-x-[Ln6L4]6- (x = 0-6) stereoisomers, racemic Δ6- and Λ6-[Ln6L4]6- could be exclusively obtained from the first self-assembly of Δ6- and Λ6-[Ln6(H3L)4]6+ under neutral conditions followed by post-assembly deprotonation. Rich isomerism on the tetra-capped octahedral cages arising from the coupling between the metal-centered Δ/Λ chirality and the ligand conformations has been discussed based on X-ray single-crystal structures of the C3-symmetric Δ3Λ3-Ln6L4 and T-symmetric Δ6/Λ6-Ln6L4 complexes. Host-guest studies confirmed that positively charged rac-Δ6/Λ6-[Ln6(H3L)4]6+ could bind anionic sulfonates, and negatively charged rac-Δ6/Λ6-[Ln6L4]6- exhibited strong encapsulation ability toward ammonium guests, where acid/base-triggered guest uptake/release could be realized taking advantage of the charge reversibility of the cage. Moreover, photophysical studies revealed visible-light-sensitized and guest-encapsulation-enhanced NIR emissions on the rac-Δ6/Λ6-Yb6L4 cage. This work not only enriches the library of functional lanthanide-organic cages but also provides a promising candidate with charge reversibility for the development of smart supramolecular materials.

MIB-ANet: A novel multi-scale deep network for nasal endoscopy-based adenoid hypertrophy grading.

Introduction: To develop a novel deep learning model to automatically grade adenoid hypertrophy, based on nasal endoscopy, and asses its performance with that of E.N.T. clinicians. Methods: A total of 3,179 nasoendoscopic images, including 4-grade adenoid hypertrophy (Parikh grading standard, 2006), were collected to develop and test deep neural networks. MIB-ANet, a novel multi-scale grading network, was created for adenoid hypertrophy grading. A comparison between MIB-ANet and E.N.T. clinicians was conducted. Results: In the SYSU-SZU-EA Dataset, the MIB-ANet achieved 0.76251 F1 score and 0.76807 accuracy, and showed the best classification performance among all of the networks. The visualized heatmaps show that MIB-ANet can detect whether adenoid contact with adjacent tissues, which was interpretable for clinical decision. MIB-ANet achieved at least 6.38% higher F1 score and 4.31% higher accuracy than the junior E.N.T. clinician, with much higher (80× faster) diagnosing speed. Discussion: The novel multi-scale grading network MIB-ANet, designed for adenoid hypertrophy, achieved better classification performance than four classical CNNs and the junior E.N.T. clinician. Nonetheless, further studies are required to improve the accuracy of MIB-ANet.

Association of obesity under different metabolic status with adverse outcomes in patients with chronic myeloid leukemia: A retrospective cohort study.

BACKGROUND: Little is known about the association between abnormal metabolic obesity states and the outcomes of chronic myeloid leukemia (CML), especially in patients with obesity with different metabolic status. Here, we used the Nationwide Readmissions Database to assess the effects of metabolically defined obesity on adverse outcomes of CML. METHODS: Of the 35 460 557 (weighted) patients, we included 7931 adults with discharge diagnoses of CML from January 1, 2018 to June 30, 2018. The study population was observed until December 31, 2018 and divided into four groups based on body mass index and metabolic status. The primary outcome was the adverse outcomes of CML, including nonremission (NR)/relapse and severe mortality risk. Multivariate logistic regression analysis was performed to analyze data. RESULTS: Metabolically unhealthy normal weight and metabolically unhealthy obesity were all risk factors for adverse outcomes of CML compared with metabolically healthy normal weight (all p < 0.01), and a significant difference was not found in the metabolically healthy obese. Female patients with metabolically unhealthy normal weight and metabolically unhealthy obesity had 1.23-fold and 1.40-fold increased NR/relapse risk, while male patients did not have this risk. Moreover, patients with a higher number of metabolic risk factors or with dyslipidemia were at higher risk of adverse outcomes, regardless of obesity status. CONCLUSIONS: Metabolic abnormalities were associated with adverse outcomes in patients with CML, irrespective of obesity status. Future treatment of patients with CML should consider the effects of obesity on their adverse outcomes under different metabolic status, especially in female patients.

Changes in Clinical Manifestations Due to AFLD Retyping Based on the New MAFLD Criteria: An Observational Study Based on the National Inpatient Sample Database.

(1) Background: As the introduction of "positive" diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) does not exclude alcohol consumption, some patients originally diagnosed with alcoholic fatty liver disease (AFLD) may be diagnosed with dual- etiology fatty liver disease (AFLD&MAFLD), which requires us to urgently explore the impact of the changes in this classification of AFLD on clinical manifestations. (2) Methods: Utilizing data from the Nationwide Inpatient Sample database 2016-2018, a total of 9269 participants with AFLD were selected. With the definition of MAFLD, these patients were further categorized into two groups: single AFLD and AFLD&MAFLD. The primary outcome was the risk of comorbidities and organ failures. The secondary outcomes were the length of stay, total charges, and in-hospital all-cause mortality. (3) Results: The patients with AFLD&MAFLD were older, were predominantly male, and had more comorbidities and organ failures compared to the patients with AFLD. These comorbidities included coronary atherosclerosis, myocardial infarction, cerebrovascular disease, arrhythmia, asthma, chronic obstructive pulmonary disease, and chronic kidney disease (all p values < 0.05). The patients with AFLD&MAFLD were more likely to develop acute and chronic heart and/or kidney failures than those with single AFLD (all p < 0.05). The length of stay and total charges of the patients in the AFLD&MAFLD group were greater than the single AFLD group (p = 0.029 and p < 0.001, respectively). No significant difference in all-cause mortality was observed. (4) Conclusions: The patients with AFLD&MAFLD have more comorbidities and organ failures, longer hospital stays, and higher hospitalization costs than the patients with single AFLD. Hence, patients with dual-etiology fatty liver disease deserve more attention from clinical staff during treatment.

Immune Infiltration Represents Potential Diagnostic and Prognostic Biomarkers for Esophageal Squamous Cell Carcinoma.

Background: Immune infiltrates in the tumor microenvironment have established roles in tumor growth, invasion, and metastasis. However, the diagnostic and prognostic potential of immune cell signature in esophageal squamous cell carcinoma (ESCC) remains unclear. Results: The proportions of 22 subsets of immune cells from 331 samples including 205 ESCC and 126 normal esophageal mucosa retrieved from TCGA, GEO, and GTEx databases were deciphered by CIBERSORT. Nine overlapping subsets of immune cells were identified as important features for discrimination of ESCC from normal tissue in the training cohort by LASSO and Boruta algorithms. A diagnostic immune score (DIS) developed by XGBoost showed high specificities and sensitivities in the training cohort, the internal validation cohort, and the external validation cohort (AUC: 0.999, 0.813, and 0.966, respectively). Furthermore, the prognostic immune score (PIS) was developed based on naive B cells and plasma cells using Cox proportional hazards model. The PIS, an independent prognostic predictor, classified patients with ESCC into low- and high-risk subgroups in the internal validation cohort (P = 0.038) and the external validation cohort (P = 0.022). In addition, a nomogram model comprising age, N stage, TNM stage, and PIS was constructed and performed excellent (HR = 4.17, 95% CI: 2.22-7.69, P < 0.0001) in all ESCC patients, with a time-dependent 5-year AUC of 0.745 (95% CI: 0.644 to 0.845), compared with PIS or TNM stage as a prognostic model alone. Conclusion: Our DIS, PIS, and nomogram models based on infiltrated immune features may aid diagnosis and survival prediction for patients with ESCC.

Endoscopic Endonasal Trans-Agger Nasi Approach for Resection of Ossifying Fibroma Involving the Anterior Skull Base: Surgical Anatomy and Technical Note.

OBJECTIVE: A variety of approaches for resection of the ossifying fibromas in sinonasal cavities have been described. However, for those involving the anterior skull base, endoscopic surgery remains challenging because of limitations in identification of tumor boundaries from the anterior skull base and proper control of the tumor-feeding vessel. This study aimed to describe a technique for resection of ossifying fibromas involving the anterior skull base through an endoscopic endonasal trans-agger nasi approach, based on anatomic studies and surgeries. METHODS: Two human cadaveric heads were prepared for study of the anatomic relationship between agger nasi and anterior skull base. Two clinical cases were used to illustrate the technique and feasibility of the approach. RESULTS: The agger nasi was located anterior and inferior to the frontal ostium and the anterior skull base. The frontal ostium and anterior skull base could be visualized and accessed under the 0-degree endoscope by removing the agger nasi. Application of the endoscopic endonasal trans-agger nasi approach in the two patients resulted in complete resection of the tumors with no surgical complications. CONCLUSIONS: An endoscopic endonasal trans-agger nasi approach provides a direct access to the anterior skull base. It would be feasible, effective, and safe for selected cases of ossifying fibroma involving anterior skull base.

N-doped CoAl oxides from hydrotalcites with enhanced oxygen vacancies for excellent low-temperature propane oxidation.

A series of nitrogen-doped CoAlO (N-CoAlO) were constructed by a hydrothermal route combined with a controllable NH3 treatment strategy. The effects of NH3 treatment on the physico-chemical properties and oxidation activities of N-CoAlO catalysts were investigated. In comparison to CoAlO, a smallest content decrease in surface Co3+ (serving as active sites) while a largest increased amount of surface Co2+ (contributing to oxygen species) are obtained over N-CoAlO/4h among the N-CoAlO catalysts. Meanwhile, a maximum N doping is found over N-CoAlO/4h. As a result, N-CoAlO/4h (under NH3 treatment at 400°C for 4 hr) with rich oxygen vacancies shows optimal catalytic activity, with a T90 (the temperature required to reach a 90% conversion of propane) at 266°C. The more oxygen vacancies are caused by the co-operative effects of N doping and suitable reduction of Co3+ for N-CoAlO/4h, leading to an enhanced oxygen mobility, which in turn promotes C3H8 total oxidation activity dominated by Langmuir-Hinshelwood mechanism. Moreover, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTs) analysis shows that N doping facilities the decomposition of intermediate species (propylene and formate) into CO2 over the catalyst surface of N-CoAlO/4h more easily. Our reported design in this work will provide a promising way to develop abundant oxygen vacancies of Co-based catalysts derived from hydrotalcites by a simple NH3 treatment.

Association between sarcopenia and prognosis of hepatocellular carcinoma: A systematic review and meta-analysis.

Background: Sarcopenia, characterized by the loss of muscle mass, strength, and physical ability, occurs with aging and certain chronic illnesses such as chronic liver diseases and cancer. Sarcopenia is common in liver cirrhosis and hepatocellular carcinoma (HCC). Previous reports of association between sarcopenia and prognosis of HCC have been inconsistent. Therefore, the present systematic review and meta-analysis aimed to investigate the impact of sarcopenia on the survival of patients with HCC. Methods: A systematic literature search was conducted using PubMed, EMBASE, and Web of Science electronic databases from inception to May 1, 2022. We included retrospective or prospective studies investigating the association between sarcopenia and overall survival (OS) and/or progression free survival (PFS) of HCC. We applied the Quality in Prognosis Studies (QUIPS) instrument to evaluate the risk of bias and quality of included studies. The primary and secondary outcomes were the associations of sarcopenia with OS and PFS, respectively, expressed by a pooled hazard ratio (HR) and corresponding 95% confidence interval (CI). Subgroup analysis and sensitivity analysis were performed. We further evaluated the publication bias by the funnel plot and Begg's test. Results: A total of 42 studies comprising 8,445 patients were included. The majority of included studies were at an overall low risk of bias. The pooled prevalence of sarcopenia was 39% (95% CI: 33-45%) (n = 8,203). Sarcopenia was associated with an increased risk of shorter OS, with a pooled adjusted HR of 1.84 (95% CI: 1.62-2.09). An independent association between sarcopenia and reduced PFS was observed (HR = 1.33, 95% CI: 1.12-1.56). Conclusion: The prevalence of sarcopenia was approximately 39% among patients with HCC. Sarcopenia was independently associated with reduced OS and PFS in HCC irrespective of treatment modalities. It is imperative that interventions aimed at alleviating sarcopenia and restoring muscle mass be implemented in order to improve the survival of patients with HCC. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337797], identifier [CRD42022337797].

Using a machine learning approach to identify key prognostic molecules for esophageal squamous cell carcinoma.

BACKGROUND: A plethora of prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) that have hitherto been reported are challenged with low reproducibility due to high molecular heterogeneity of ESCC. The purpose of this study was to identify the optimal biomarkers for ESCC using machine learning algorithms. METHODS: Biomarkers related to clinical survival, recurrence or therapeutic response of patients with ESCC were determined through literature database searching. Forty-eight biomarkers linked to recurrence or prognosis of ESCC were used to construct a molecular interaction network based on NetBox and then to identify the functional modules. Publicably available mRNA transcriptome data of ESCC downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets included GSE53625 and TCGA-ESCC. Five machine learning algorithms, including logical regression (LR), support vector machine (SVM), artificial neural network (ANN), random forest (RF) and XGBoost, were used to develop classifiers for prognostic classification for feature selection. The area under ROC curve (AUC) was used to evaluate the performance of the prognostic classifiers. The importances of identified molecules were ranked by their occurrence frequencies in the prognostic classifiers. Kaplan-Meier survival analysis and log-rank test were performed to determine the statistical significance of overall survival. RESULTS: A total of 48 clinically proven molecules associated with ESCC progression were used to construct a molecular interaction network with 3 functional modules comprising 17 component molecules. The 131,071 prognostic classifiers using these 17 molecules were built for each machine learning algorithm. Using the occurrence frequencies in the prognostic classifiers with AUCs greater than the mean value of all 131,071 AUCs to rank importances of these 17 molecules, stratifin encoded by SFN was identified as the optimal prognostic biomarker for ESCC, whose performance was further validated in another 2 independent cohorts. CONCLUSION: The occurrence frequencies across various feature selection approaches reflect the degree of clinical importance and stratifin is an optimal prognostic biomarker for ESCC.

Base- and Metal-Dependent Self-Assembly of Lathanide-Organic Coordination Polymers or Macrocycles with Tetradentate Acylhydrazone-based Ditopic Ligands.

Herein, we report a comprehensive study on the lanthanide-directed coordination self-assembly with two bis-tetradentate acylhydrazone ligands H4 L1 and H4 L2 . Multifarious outcomes, which are base- and metal-dependent, were revealed by NMR, ESI-TOF-MS and X-ray crystallography. In the absence of base, bent H4 L1 was assembled into dinuclear double-strand helicate Ln2 (H2 L1 )2 by partially-deprotonated assembly with La, Sm or Eu, while trinuclear Ln3 (H2 L1 )3 with Yb or Lu. For linear H4 L2 , infinite 1D zig-zag metal-organic polymeric chain (Ln2 H2 L2 )n was obtained. However, complete deprotonated L1 and L2 assembled into discrete trinuclear Ln3 (L1 /2 )3 and tetranuclear Ln4 (L1 /2 )4 macrocyclic structures under the basic condition. For these, there are multiple possible isomers coexisting in the solution which were enumerated and simulated with molecular mechanic modeling. Visible-light sensitized NIR emissions on the Yb complexes have been observed, endowing them potential application in photofunctional materials.

Modified adenoid grading system for evaluating adenoid size in children: a prospective validation study.

Nasal endoscopy is the best choice for evaluation of adenoid size, but very few studies published on the endoscopic quantitative assessment. This study aimed to newly propose and validate a modified adenoid grading system (MAGS) with the existing endoscopic scoring methods of adenoid size. A prospective study on children with chronic mouth breathing and having endoscopic nasal examination was conducted. Digital images obtained during endoscopic examination were evaluated with the traditional method and the MGAS. Adenoid size was also evaluated by intraoperative nasal endoscopy among those underwent adenoidectomy. One hundred and thirty patients were enrolled. The MAGS showed high inter-rater reliability with a Kappa score of 0.869. Sixty of 130 patients underwent adenoidectomy and assessed with intraoperative nasal endoscopy. The MAGS significantly correlated to the percentage of nasopharyngeal obstruction of intraoperative endoscopy (Spearman's r = 0.796, gamma coefficient = 0.94), and the percentage of choanal obstruction of preoperative endoscopy (Spearman's r = 0.816, gamma coefficient = 0.859). Our findings suggest that the MAGS has high reliability and validity for assessment of adenoid size. It may be a more suitable and reliable grading system for endoscopic evaluation of adenoid size.

Boosting total oxidation of propane over CeO2@Co3O4 nanofiber catalysts prepared by multifluidic coaxial electrospinning with continuous grain boundary and fast lattice oxygen mobility.

A one-dimensional (1D) core-shell of Co-Ce oxide has been prepared by multifluidic coaxial electrospinning method and evaluated for the total oxidation of propane (C3H8). Activity and morphological characterizations show that the CeO2@Co3O4 nanofiber catalyst, of which the core is CeO2 and the shell is Co3O4, exhibits excellent oxidation activity. The exposed Co3O4 grown on the outside of the fibers can rapidly react with C3H8 while CeO2 with high oxygen storage capacity in the inside is conductive to the enhanced oxidation rate. Besides, the continuous grain boundary provides a fast mass transfer channel for lattice oxygen, and rich oxygen vacancies favor the mobility of active oxygen species. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTs) confirms that the CeO2@Co3O4 catalyst have a faster rate of C3H8 adsorption and better oxidation activity with respect to the counterpart using a single-needle electrospinning method. Moreover, the CeO2@Co3O4 catalyst displays excellent thermal stability, and strong resistance against 5 vol% H2O and 5 vol% CO2 at both 300 and 400 °C. Our strategy can give some new insights into morphological engineering to promote active oxygen mobility via the construction of one-dimensional core-shell of metal oxides for catalytic oxidation of VOCs.

Porphyromonas gingivalis promotes progression of esophageal squamous cell cancer via TGFß-dependent Smad/YAP/TAZ signaling.

Microbial dysbiosis in the upper digestive tract is linked to an increased risk of esophageal squamous cell carcinoma (ESCC). Overabundance of Porphyromonas gingivalis is associated with shorter survival of ESCC patients. We investigated the molecular mechanisms driving aggressive progression of ESCC by P. gingivalis. Intracellular invasion of P. gingivalis potentiated proliferation, migration, invasion, and metastasis abilities of ESCC cells via transforming growth factor-ß (TGFß)-dependent Drosophila mothers against decapentaplegic homologs (Smads)/Yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) activation. Smads/YAP/TAZ/TEA domain transcription factor1 (TEAD1) complex formation was essential to initiate downstream target gene expression, inducing an epithelial-mesenchymal transition (EMT) and stemness features. Furthermore, P. gingivalis augmented secretion and bioactivity of TGFß through glycoprotein A repetitions predominant (GARP) up-regulation. Accordingly, disruption of either the GARP/TGFß axis or its activated Smads/YAP/TAZ complex abrogated the tumor-promoting role of P. gingivalis. P. gingivalis signature genes based on its activated effector molecules can efficiently distinguish ESCC patients into low- and high-risk groups. Targeting P. gingivalis or its activated effectors may provide novel insights into clinical management of ESCC.

MicroRNA-320d regulates tumor growth and invasion by promoting FoxM1 and predicts poor outcome in gastric cardiac adenocarcinoma.

Recent evidences demonstrate that dysregulated expression of microRNA-320d (miR-320d) has been associated with several cancer development and progression. However the effect of miR-320d on gastric cardiac adenocarcinoma (GCA) and the association of miR-320d with its potential gene target FoxM1 remain unclear. Here, we evaluated expression profile of miR-320d and FoxM1 in 60 human GCA tissues and GCA cell lines (OE-19 and SK-GT2). Immunohistochemistry, qualitative PCR and western-blotting were performed in GCA tissues to detect the expression level of miR-320d and FoxM1. CCK-8, transwell, wound-healing assays, and in vivo experiments were conducted using GCA cells that treated with miR-320d mimics or inhibitors to evaluate the biological functions of miR-320d. Luciferase reporter assay was conducted to confirm possible binding sites of FoxM1 for miR-320d. Compared with paired non-cancerous tissues, it showed that miR-320d expression was significantly decreased in GCA specimens (P < 0.0001), while FoxM1 was significantly upregulated in GCA tissues (P < 0.0001). Modulating miR-320d function by transfection of miR-320 mimics or inhibitor led to inhibition or promotion of GCA cell proliferation and invasion, thus regulating tumor progression in GCA-tumor bearing mice. The mechanism analysis of miR-320d/FoxM1 showed that FoxM1 has two miR-320d binding sites in its 3'-untranslated region (3'-UTR), that contributes to regulation of the cell biological behaviors. Taken together, our data suggested that miR-320d acts as a tumor suppressor in GCA by directly targeting FoxM1 and thus potentially serves as a biomarker for anti-GCA therapy in GCA patients.

Controllable P Doping of the LaCoO3 Catalyst for Efficient Propane Oxidation: Optimized Surface Co Distribution and Enhanced Oxygen Vacancies.

The properties of LaCoO3 are modified by a controllable P doping strategy via a simple sol-gel route. It is demonstrated that appropriate P doping is beneficial for forming a relatively pure perovskite phase and hinders the growth of perovskite nanoparticles. The combined results of density functional theory (DFT), extended X-ray absorption fine structure (EXAFS), X-ray absorption near-edge structure (XANES), temperature-programmed reduction of hydrogen (H2-TPR), X-ray photoelectron spectroscopy (XPS), and temperature-programmed desorption of ammonia (NH3-TPD) reveal that appropriate P doping gives rise to more oxygen vacancies, optimized distribution of Co ions, and improved surface acidity, which are beneficial for the adsorption of active oxygen species and the activation of propane molecules, resulting in an excellent catalytic oxidation performance. Especially, LaCo0.97P0.03O3 exhibits more surface-active oxygen species, higher bulk Co3+ proportion, increased surface Co2+ species, and increased acidity, resulting in its superior propane oxidation performance, which is dominated by the Langmuir-Hinshelwood mechanism. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) confirms that the presence of P will accelerate oxygen mobility, which in turn promotes the oxidation rate. Moreover, the obtained LaCo0.97P0.03O3 catalyst displays excellent thermal stability during the 60 h durability test at 400 °C and strong resistance against 5 vol % H2O and/or 5 vol % CO2 for prolonged 150 h.

miR-200b/c-RAP1B axis represses tumorigenesis and malignant progression of papillary thyroid carcinoma through inhibiting the NF-κB/Twist1 pathway.

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with an increasing occurrence and recurrence. MicroRNAs (miRNAs) have been widely acknowledged to be participated in human cancers. However, how these miRNAs exert roles and potential mechanisms in PTC regulatory networks is still lacking. The purpose of our study lies in discovering the regulatory basis of miR-200b/c and Rap1b for PTC tumorigenesis and malignant progression, as well as the underlying molecular mechanisms. Herein, miR-200b/c expression was sharply dropped and Rap1b expression was up-regulated in PTC cells and tissues samples when compared to normal thyroid epithelial cells and normal tissues. miR-200b/c targeted Rap1 directly and negatively regulated its expression. miR-200b/c overexpression suppressed proliferative, colony forming, migratory and invasive capabilities and EMT as well as elevated apoptosis of PTC cells through inhibiting Rap1b. Furthermore, xenograft experiments showed miR-200b/c overexpression constrained growth of PTC xenograft and EMT. miR-200b/c inhibited NF-κB/Twist1 signals via regulating the Rap1b expression in cells and animal models. Taken together, our study suggested that upregulation of miR-200b/c-RAP1B axis constrained PTC cell proliferation, invasion, migration and EMT. Also, the upregulation of miR-200b/c-RAP1B leaded to elevated apoptosis through inhibiting the NF-κB/Twist1 pathway, thus inhibiting PTC tumorigenesis and malignant progression.

SENP2 suppresses NF-κB activation and sensitizes breast cancer cells to doxorubicin.

Doxorubicin is a chemotherapeutic agent commonly used to treat breast cancer. However, breast cancer often develops drug resistance, leading to disease recurrence and poor prognosis. Delineating the mechanisms underlying drug resistance is imperative for overcoming the challenge of treating doxorubicin-resistant breast cancer. In this study, by identifying the possible role of Sentrin/SUMO-specific proteases (SENPs) in doxorubicin resistance, we show here that among the 6 members of SENPs, only SENP2 is downregulated in doxorubicin-resistant MCF-7 (MCF-7/adr) and MDA-MB-231 (dr) breast cancer cells, as compared with sensitive counterparts. In addition, functionally, SENP2 overexpression resensitizes resistant breast cancer cells to doxorubicin treatment, and its knockdown confers doxorubicin resistance in sensitive ones. Moreover, NF-κB pathway is activated in MCF-7/adr cells, however, treatment with Bay 11-7085, one specific inhibitor of this pathway, reverses resistance to doxorubicin, suggesting that NF-κB pathway activation contributes to doxorubicin resistance in MCF-7/adr cells. We further show that SENP2 overexpression enhances NEMO deSUMOylation and suppresses NF-κB activation particularly in MCF-7/adr cells. Furthermore, SENP2 overexpression-induced sensitivity of MCF-7/adr cells to doxorubicin is drastically abrogated when treated with NF-κB pathway activator, thus establishing a causal link between SENP2-suppressed NF-κB pathway and enhanced doxorubicin sensitivity in breast cancer cells. Overall, this study reveals a novel function of SENP2 in counteracting doxorubicin resistance in breast cancer, and highlights the critical role of NF-κB suppression in mediating this effect.

An Sn doped 1T-2H MoS2 few-layer structure embedded in N/P co-doped bio-carbon for high performance sodium-ion batteries.

A facile method for fabricating Sn doped 1T-2H MoS2 embedded in N/P co-doped bio-carbon is developed using natural chlorella as an adsorbent and a nanoreactor. When used as an anode for sodium-ion batteries, it delivers an excellent rate performance (167 mA h g-1 at 15 A g-1), high capacity (533 mA h g-1 after 50 cycles at 0.1 A g-1), and superior long-term cycling stability (320 mA h g-1 after 500 cycles at 1 A g-1) which are attributed to the synergistic effects of few-layer 1T-2H MoS2 moderate Sn doping and the N/P co-doped bio-carbon.