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The stable electrode/electrolyte interface and fast electron/ion transport channel play important roles in boosting the rate performance and cycling life of lithium-ion batteries. Herein, a porous silicon/carbon composite (pSi@PC@MC) is presented by integrating hollow porous silicon (pSi) with pitch-derived carbon (PC) and dopamine-derived mesoporous carbon (MC), employing microporous zeolite as the silicon source. The finite element simulation first reveals the stress release effect of rigid and flexible carbon encapsulation on the hollow Si anode for lithium-ion storage. In situ and ex situ characterization results further elucidate that hybrid sp 2 /sp 3 carbon coating greatly enhances the liquid/solid interface stability and the compatibility with the electrolyte, as well as facilitates the electron/ion transmission dynamics, achieving a uniform, stable, and LiF-rich SEI film, ultimately improving the lithium storage performance. As expected, the as-designed pSi@PC@MC anode delivers an impressive rate capability (756.6 mAh g -1 at 6 A g -1 ) and excellent cycling stability with a capacity of 1650 mAh g -1 after 300 cycles at 0.2 A g -1 . Meanwhile, the pSi@PC@MC//NCM811 full-cell exhibits an outstanding cycling stability (75.8% capacity retention after 100 cycles). This study highlights the significance of rational porous design and effective hybrid carbon encapsulation for the development of fast-charging Si/carbon anodes., (© 2024 Wiley‐VCH GmbH.)

Background and Aims: The Hippo signaling has emerged as a crucial regulator of tissue homeostasis, regeneration, and tumorigenesis, representing a promising therapeutic target. Neurofibromin 2 (NF2), a component of Hippo signaling, is directly linked to human cancers but has been overlooked as a target for cancer therapy., Approach and Results: Through a high-content RNA interference genome-wide screen, the actin-binding protein Drebrin (DBN1) has been identified as a novel modulator of YAP localization. Further investigations have revealed that DBN1 directly interacts with NF2, disrupting the activation of large tumor suppressor kinases (LATS1/2) by competing with LATS kinases for NF2 binding. Consequently, DBN1 knockout considerably promotes YAP nuclear exclusion and repression of target gene expression, thereby preventing cell proliferation and liver tumorigenesis. We identified three lysine residues (K238, K248, and K252) essential for DBN1-NF2 interaction and developed a mutant DBN1 (DBN1-3Kmut) that is defective in NF2 binding and incompetent to trigger NF2-dependent YAP activation and tumorigenesis both in vitro and in vivo. Furthermore, BTP2, a DBN1 inhibitor, successfully restored NF2-LATS kinase binding and elicited potent antitumor activity. The combination of sorafenib and BTP2 exerted synergistic inhibitory effects against HCC., Conclusions: Our study identifies a novel DBN1-NF2-LATS axis, and pharmacological inhibition of DBN1 represents a promising alternative intervention targeting the Hippo pathway in cancer treatment., (Copyright © 2024 American Association for the Study of Liver Diseases.)

The rational design of MoS 2 /carbon composites have been widely used to improve the lithium storage capability. However, their deep applications remain a big challenge due to the slow electrochemical reaction kinetics of MoS 2 and weak bonding between MoS 2 and carbon substrates. In this work, anthracite-derived porous carbon (APC) is sequential coated by TiO 2 nanoparticles and MoS 2 nanosheets via a chemical activation and two-step hydrothermal method, forming the unique APC@TiO 2 @MoS 2 ternary composite. The dynamic analysis, in-situ electrochemical impedance spectroscopy as well as theoretical calculation together demonstrate that this innovative design effectively improves the ion/electron transport behavior and alleviates the large volume expansion during cycles. Furthermore, the introduction of middle TiO 2 layer in the composite significantly strengthens the mechanical stability of the entire electrode. As expected, the as-prepared APC@TiO 2 @MoS 2 anode displays a high lithium storage capacity with a reversible capacity of 655.8 mAh g -1 after 150 cycles at 200 mA g -1 , and robust cycle stability. Impressively, even at a high current density of 2 A g -1 , the electrode maintains a superior reversible capacity of 597.7 mAh g -1 after 1100 cycles. This design highlights a feasibility for the development of low-cost anthracite-derived porous carbon-based electrodes., (© 2024 Wiley-VCH GmbH.)

Establishing a durable interfacial layer between an electrode and electrolyte to enable micron-sized silicon-based lithium-ion battery (LIB) anodes to achieve superior electrochemical performance is highly desired. Recent studies have shown that heterogeneous encapsulation with enhanced ion/electron transport is an effective strategy. However, the structural design of the existing hetero-coated interface lacks a reasonable ion/electron transport channel, resulting in high interfacial impedance. Herein, we designed a heterogenous MXene-mesoporous polypyrrole (mPPy) encapsulation layer onto micron-sized SiO particles. The MXene coating layer functions as a bridging interface that can build a strong chemical link to internal SiO via covalent bonding, thus reinforcing interfacial charge transfer rate. Meanwhile, it forms a dynamic connection with the outer mPPy through hydrogen bonding, which contributes to high interfacial Li + concentration and ion/electron coupling transport rate. Accordingly, the as-prepared SiO@MXene@mPPy anode delivers a boosted specific capacity of 673.9 mA h g -1 at 2 A g -1 after 1000 cycles and high-rate capability of 777.4 mA h g -1 at 5 A g -1 . Further, electrochemical kinetic analysis indicates that the MXene@mPPy coating layer shows a pseudocapacitance controlled Li storage mechanism, thereby displaying improved high-rate capability. This porous hybrid encapsulation strategy offers new possibilities for a micron-sized SiO anode to achieve an excellent performance.

Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essential. Here, we identified that an underappreciated serine/threonine kinase, cyclin-dependent kinase-like 3 (CDKL3), crucially drives rapid cell cycle progression and cell growth in cancers. With regard to mechanism, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of cyclin-dependent kinase 4 (CDK4) by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized, and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes acquired resistance to CDK4/6 inhibitor. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presents an integrated paradigm of cancer cell cycle regulation and suggests CDKL3 targeting as a feasible approach in cancer treatment.

Upregulation of the Wilms' tumour 1 (WT1) gene is common in acute myeloid leukaemia (AML) and is associated with poor prognosis. WT1 generates 12 primary transcripts through different translation initiation sites and alternative splicing. The short WT1 transcripts express abundantly in primary leukaemia samples. We observed that overexpression of short WT1 transcripts lacking exon 5 with and without the KTS motif (sWT1+/- and sWT1-/-) led to reduced cell growth. However, only sWT1+/- overexpression resulted in decreased CD71 expression, G1 arrest, and cytarabine resistance. Primary AML patient cells with low CD71 expression exhibit resistance to cytarabine, suggesting that CD71 may serve as a potential biomarker for chemotherapy. RNAseq differential expressed gene analysis identified two transcription factors, HOXA3 and GATA2, that are specifically upregulated in sWT1+/- cells, whereas CDKN1A is upregulated in sWT1-/- cells. Overexpression of either HOXA3 or GATA2 reproduced the effects of sWT1+/-, including decreased cell growth, G1 arrest, reduced CD71 expression and cytarabine resistance. HOXA3 expression correlates with chemotherapy response and overall survival in NPM1 mutation-negative leukaemia specimens. Overexpression of HOXA3 leads to drug resistance against a broad spectrum of chemotherapeutic agents. Our results suggest that WT1 regulates cell proliferation and drug sensitivity in an isoform-specific manner., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The success of solid organ transplantation (SOT) and the use of immunosuppressive agents offer hope to patients with end-stage diseases. However, the impact of post-transplant diabetes mellitus (PTDM) on SOT patients has become increasingly evident. In our study, we utilized the Scientific Registry of Transplant Recipients (SRTR) database to investigate the association between PTDM and patient survival in various types of organ transplantations, including liver, kidney, intestinal, heart, lung, and combined heart-lung transplantations (all P <0.001). Our findings revealed a negative effect of PTDM on the survival of these patients. Furthermore, we examined the effects of both generic and innovator immunosuppressive agents on the development of PTDM and the overall survival of different SOT populations. Interestingly, the results were inconsistent, indicating that the impact of these agents may vary depending on the specific type of transplantation and patient population. Overall, our study provides a comprehensive and systematic assessment of the effects of different immunosuppressive agents on prognosis, as well as the impact of PTDM on the survival of patients undergoing various types of SOT. These findings emphasize the need for further research and highlight the importance of optimizing immunosuppressive regimens and managing PTDM in SOT patients to improve their long-term outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: With the aging of the population, colorectal surgeons will have to face more elderly colorectal cancer (CRC) patients in the future. We aim to analyze independent risk factors affecting overall survival in elderly (age ≥65 years) patients with stage II-III CRC and construct a nomogram to predict patient survival., Methods: A total of 3,016 elderly CRC patients with stage II-III were obtained from the SEER database. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen independent prognostic factors, and a survival prediction nomogram was constructed based on the results. The consistency index (C-index), decision curve analysis (DCA), Akaike information criterion (AIC), and Bayesian information criterion (BIC) were used to compare the predictive ability between the nomogram and tumor-node-metastasis (TNM) stage system. All patients were classified into high-risk and low-risk groups based on risk scores calculated by nomogram. The Kaplan-Meier method was used to compare the survival differences between two groups., Results: The 3- and 5-year area under the curve (AUC) values of the prediction nomogram model were 76.6% and 74.8%, respectively. The AIC, BIC, and C-index values of the nomogram model were 6,032.502, 15,728.72, and 0.707, respectively, which were better than the TNM staging system. Kaplan-Meier survival analysis showed a significant survival difference between high-risk and low-risk groups (P<0.0001)., Conclusions: We constructed a prediction nomogram for stage II-III elderly CRC patients by combining pre-treatment carcinoembryonic antigen (CEA) levels, which can accurately predict patient survival. This facilitates clinicians to accurately assess patient prognosis and identify high-risk patients to adopt more aggressive and effective treatment strategies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-863/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

The development of a high-rate SiO lithium-ion battery anode is seriously limited by its low intrinsic conductivity, sluggish interfacial charge transfer (ICT), and unstable dynamic interface. To tackle the above issues, interfacial encapsulation engineering for effectively regulating the interfacial reaction and thus realizing a stable solid electrolyte interphase is significantly important. Hybrid coating, which aims to enhance the coupled e - /Li + transport via the employment of dual layers, has emerged as a promising strategy. Herein, we construct a hybrid MXene-graphene oxide (GO) coating layer on the SiO microparticles. In the design, Ti 3 C 2 T x MXene acts as a "bridge", which forms a close covalent connection with SiO and GO through Ti-O-Si and Ti-O-C bonds, respectively, thus greatly reducing the ICT resistance. Moreover, the Ti 3 C 2 T x with rich surface groups (e.g., -OH, -F) and GO outer layers with an intertwined porous framework synergistically enable the pseudocapacitance dominated behavior, which is beneficial for fast lithium-ion storage. Accordingly, the as-made Si@MXene@GO anode exhibits considerably reinforced lithium-ion storage performance in terms of superior rate performance (1175.9 mA h g -1 at 5 A g -1 ) and long cycling stability (1087.6 mA h g -1 capacity retained after 1000 cycles at 2.0 A g -1 ). In-depth interfacial chemical composition analysis further reveals that an inorganically rich interphase with a gradient distribution of LiF and Li 2 O formed at the electrolyte/anode interface ensures mechanical stability during repeated cycles. This work paves a feasible way for maximizing the potential of SiO anodes toward fast-charging lithium-ion batteries.

Flap endonuclease 1 (FEN1) is a structure-specific nuclease that is involved in the occurrence and development of various types of tumors. Previous studies have shown that FEN1 plays an important role in the development of hepatocellular carcinoma, however, the molecular mechanisms remain fully elucidated, especially its effect on the cell cycle of hepatocellular carcinoma has not been investigated. In this study, via bioinformatics prediction and clinical specimen verification, we confirmed that FEN1 was highly expressed in HCC and correlated with poor prognosis. The knockdown or overexpression of FEN1 could inhibit or promote the proliferation and invasion of HCC cells. Importantly, cell cycle and functional experiments showed that FEN1 could promote cell proliferation by inducing cell cycle transition from G2 to M phase. Further studies indicated that FEN1 regulated the G2/M transition by modulating cell division cycle 25C (Cdc25C), cyclin-dependent kinase 1 (CDK1) and Cyclin B1 expressions. To sum up, our research suggested that FEN1 could promote the proliferation, migration and invasion of HCC cells via activating cell cycle progression from G2 to M phase, indicating that FEN1 may be a potential target for the treatment of HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Wnt/β-catenin signaling is a conserved pathway crucially governing development, homeostasis, and oncogenesis. Discoveries of its regulators hold great values in both basic and translational research. Through screening, we identified a deubiquitinase, USP10, as a critical modulator of β-catenin. Mechanistically, USP10 binds to key scaffold Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination. Surprisingly, USP10 physically tethers Axin1 and β-catenin and promotes the phase separation for β-catenin suppression regardless of the enzymatic activity. Function-wise, USP10 enzymatic activity preferably regulates embryonic development and both the enzymatic activity and physical function jointly control intestinal homeostasis by antagonizing β-catenin. In colorectal cancer, USP10 substantially represses cancer growth mainly through physical promotion of phase separation and correlates with Wnt/β-catenin magnitude clinically. Collectively, we discovered USP10 functioning in multiple biological processes against β-catenin and unearthed the enzyme-dependent and -independent "dual-regulating" mechanism. These two functions of USP10 work in parallel and are context dependent., Competing Interests: Declaration of interests The authors declare no conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

With the accelerated penetration of the global electric vehicle market, the demand for fast charging lithium-ion batteries (LIBs) that enable improvement of user driving efficiency and user experience is becoming increasingly significant. Robust ion/electron transport paths throughout the electrode have played a pivotal role in the progress of fast charging LIBs. Yet traditional graphite anodes lack fast ion transport channels, which suffer extremely elevated overpotential at ultrafast power outputs, resulting in lithium dendrite growth, capacity decay, and safety issues. In recent years, emergent multiscale porous anodes dedicated to building efficient ion transport channels on multiple scales offer opportunities for fast charging anodes. This review survey covers the recent advances of the emerging multiscale porous anodes for fast charging LIBs. It starts by clarifying how pore parameters such as porosity, tortuosity, and gradient affect the fast charging ability from an electrochemical kinetic perspective. We then present an overview of efforts to implement multiscale porous anodes at both material and electrode levels in diverse types of anode materials. Moreover, we critically evaluate the essential merits and limitations of several quintessential fast charging porous anodes from a practical viewpoint. Finally, we highlight the challenges and future prospects of multiscale porous fast charging anode design associated with materials and electrodes as well as crucial issues faced by the battery and management level.

Placopecten magellanicus (Gmelin, 1791), a deep-sea Atlantic scallop, holds significant commercial value as a benthic marine bivalve along the northwest Atlantic coast. Recognizing its economic importance, the need to reconstruct its genome assembly becomes apparent, fostering insights into natural resources and generic breeding potential. This study reports a high-quality chromosome-level genome of P. magellanicus, achieved through the integration of Illumina short read sequencing, PacBio HiFi sequencing, and Hi-C sequencing techniques. The resulting assembly spans 1778 Mb with a scaffold N50 of 86.71 Mb. An intriguing observation arises - the genome size of P. magellanicus surpasses that of its Pectinidae family peers by 1.80 to 2.46 times. Within this genome, 28,111 protein-coding genes were identified. Comparative genomic analysis involving five scallop species unveils the critical determinant of this expanded genome: the proliferation of repetitive sequences recently inserted, contributing to its enlarged size. The landscape of whole genome collinearity sheds light on the relationships among scallop species, enhancing our broader understanding of their genomic framework. This genome provides genomic resources for future molecular biology research on scallops and serves as a guide for the exploration of longevity-related genes in scallops., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM., Methods: We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People's Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4., Results: BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4., Conclusions: BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes., (© 2023. The Author(s).)

Background: To investigate the physical and psychological effects of five-element music therapy combined with Baduanjin qigong treatment on inpatients with mild coronavirus disease 2019 (COVID-19) in Wuhan., Methods: A mixed-methods study was used. In the quantitative study, a randomized controlled trial was performed on 40 study participants divided into a control group ( n = 20) and an intervention group ( n = 20). The Self-rating Anxiety Scale, Self-rating Depression Scale and Pittsburgh Sleep Quality Index were compared. For qualitative analysis, it adopted purposive sampling method, 13 patients of different ages from 18 to 60 years old and different exercise behavior were selected as the participants from the intervention group. A semi-structured interview method was used to collect data, and the content analysis method was used for data analysis. An interview outline was developed to assess the psychological condition and personal functional-exercise behavior of patients., Results: In the quantitative study, the anxiety self-scores and depression self-scores of patients in intervention group were significantly lower compared with control group after treatment ( p < .05). The sleep quality of intervention group was significantly improved compared with control group ( p < .001). Participants in the qualitative study responded to questions posed through semi-structured interviews. The effect of intervention was good, which has been supported and recognized by patients., Conclusion: The treatment of five-element music therapy combined with Baduanjin qigong on patients with mild COVID-19 alleviated anxiety and depression, and improved sleep quality, which was beneficial to the patients' physical and psychological recovery., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

A highly efficient g-C 3 N 4 photocatalyst is developed by a novel one-pot thermal polymerization method under a salt fog environment generated by heating the aqueous solution of urea and mixed metal salts of NaCl/KCl, namely SF-CN. Thanks to the synergistic effect of the oxygenation and chemical etching of the salt fog, the obtained SF-CN is an oxygenated ultrathin porous carbon nitride with an intermolecular triazine-heptazine heterostructure, meanwhile, shows enlarged specific surface area, greatly enhanced absorption of visible light, narrowed band gap with a lower conduction band, and an increased photocurrent response due to the effective separation of photogenerated holes and electrons, comparing to those of pristine g-C 3 N 4 . The theoretical simulations further reveal that the triazine-heptazine heterostructure possesses better photocatalytic hydrogen evolution (PHE) capability than pure triazine and heptazine carbon nitrides. In turn, SF-CN demonstrates an excellent visible light PHE rate of 18.13 mmol h -1  g -1 , up to 259.00 times of that of pristine g-C 3 N 4 ., (© 2023 Wiley-VCH GmbH.)

As an important kind of emerging heterogeneous catalyst for sustainable chemical processes, supported metal cluster (SMC) catalysts have received great attention for their outstanding activity; however, the easy aggregation of metal clusters due to their migration along the substrate's surface usually deteriorates their activity and even causes catalyst failure during cycling. Herein, stable Pt nanoclusters (NCs, ∼1.06 nm) are homogeneously confined in the uniform spherical mesopores of mesoporous titania (mpTiO 2 ) by the interaction between Pt NCs and metal oxide pore walls made of polycrystalline anatase TiO 2 . The obtained Pt-mpTiO 2 exhibits excellent stability with well-retained CO conversion (∼95.0%) and Pt NCs (∼1.20 nm) in the long term water-gas shift (WGS) reaction. More importantly, the Pt-mpTiO 2 displays an unusual increasing activity during the cyclic catalyzing WGS reaction, which was found to stem from the in situ generation of interfacial active sites (Ti 3+ -O v -Pt δ+ ) by the reduction effect of spillover hydrogen generated at the stably supported Pt NCs. The Pt-mpTiO 2 catalysts also show superior performance toward the selective hydrogenation of furfural to 2-methylfuran. This work discloses an efficient and robust Pt-mpTiO 2 catalyst and systematically elucidates the mechanism underlying its unique catalytic activity, which helps to design stable SMC catalysts with self-enhancing interfacial activity in sustainable heterogeneous catalysis., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Salmonella typhimurium (S. typhimurium) infection is one of leading causes of severe foodborne illness, which poses grievous threats to public health. Thus, the detection with ultra-sensitivity is highly demanded for timely prevention and diagnosis of S. typhimurium. In this study, we developed a novel detection machinery based on DNA walker and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas12a technologies. Mechanistically, the S. typhimurium specific sequence triggers Nt.AlwI nicking endonuclease and produces particular signaling nucleotide, which further activates Cas12a for strong fluorescence signal output. This cascade amplification strategy exhibits excellent specificity and successfully decreases the limit of detection (LOD) of DNA walker by 2,000 folds to 5 CFU/mL. Collectively, this combinatorial approach offers great promises to effectively reduce foodborne diseases by ultrasensitive detection of S. typhimurium. As a proof of concept, this innovative design also shows prominent potential in detections of other biomolecules, cells and pathogens., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Frizzled (Fzd) proteins are Wnt receptors and play essential roles in development, homeostasis, and oncogenesis. How Wnt/Fzd signaling is coupled to physiological regulation remains unknown. Cholesterol is reported as a signaling molecule regulating morphogen such as Hedgehog signaling. Despite the elusiveness of the in-depth mechanism, it is well-established that pancreatic cancer specially requires abnormal cholesterol metabolism levels for growth. In this study, it is unexpectedly found that among ten Fzds, Fzd5 has a unique capacity to bind cholesterol specifically through its conserved extracellular linker region. Cholesterol-binding enables Fzd5 palmitoylation, which is indispensable for receptor maturation and trafficking to the plasma membrane. In Wnt-addicted pancreatic ductal adenocarcinoma (PDAC), cholesterol stimulates tumor growth via Fzd5-mediated Wnt/β-catenin signaling. A natural oxysterol, 25-hydroxylsterol competes with cholesterol and inhibits Fzd5 maturation and Wnt signaling, thereby alleviating PDAC growth. This cholesterol-receptor interaction and ensuing receptor lipidation uncover a novel mechanism by which Fzd5 acts as a cholesterol sensor and pivotal connection coupling lipid metabolism to morphogen signaling. These findings further suggest that cholesterol-targeting may provide new therapeutic opportunities for treating Wnt-dependent cancers., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Osteosarcoma (OS) is a serious bone malignancy that commonly occurred in humans. Recent research suggested that circular RNA (circRNA) Dedicator of cytokinesis 1 (circDOCK1, also called hsa&#95;circ&#95;0020378) enrolled in the tumorigenesis of osteogenic sarcoma. This subject aimed to explore the precise role and mechanism of circDOCK1 on OS progression., Methods: CircDOCK1, microRNA-936 (miR-936), and Lymphoid enhancer binding factor 1 (LEF1) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, wound healing, and tube formation assays were used to assess OS cell proliferation, migration, invasion, and angiogenesis. Western blot analysis of protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2), MMP9, and LEF1. According to bioinformatics software (circular RNA Interactome and TargetScan) analysis, the binding between miR-936 and circDOCK1 or LEF1 was predicted, followed by verification by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays., Results: Increased circDOCK1 and LEF1, and decreased miR-936 were found in OS tissues and cell lines. Furthermore, circDOCK1 silencing might suppress OS cell proliferation, migration, invasion, and angiogenesis in vitro . Bioinformatics analysis exhibited that circDOCK1 acted as a sponge for miR-936 and LEF1 was a downstream target of miR-936. Moreover, circDOCK1 functions through modulation of the miR-936/LEF1 axis., Conclusion: CircDOCK1 knockdown might attenuate OS cell malignant biological behaviors by regulating the miR-936/GFRA1 axis, which may highlight the diagnostic and therapeutic potential of these molecules for OS treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Acute myeloid leukemia (AML) is a cancer of myeloid-lineage cells with limited therapeutic options. We previously combined ex vivo drug sensitivity with genomic, transcriptomic, and clinical annotations for a large cohort of AML patients, which facilitated discovery of functional genomic correlates. Here, we present a dataset that has been harmonized with our initial report to yield a cumulative cohort of 805 patients (942 specimens). We show strong cross-cohort concordance and identify features of drug response. Further, deconvoluting transcriptomic data shows that drug sensitivity is governed broadly by AML cell differentiation state, sometimes conditionally affecting other correlates of response. Finally, modeling of clinical outcome reveals a single gene, PEAR1, to be among the strongest predictors of patient survival, especially for young patients. Collectively, this report expands a large functional genomic resource, offers avenues for mechanistic exploration and drug development, and reveals tools for predicting outcome in AML., Competing Interests: Declaration of interests C.E.T. receives research support from Notable Labs and serves as a scientific liaison for AstraZeneca. J.E.M. receives research funding from Gilead Pharmaceutical and serves on a scientific advisory board for Ionis Pharmaceuticals. M.W.D. serves on the advisory boards and/or as a consultant for Novartis, Incyte, and BMS and receives research funding from BMS and Gilead. C.S.H. receives research funding from Sellas. T.L.L. consults for Jazz Pharmaceuticals and receives research funding from Tolero, Gilead, Prescient, Ono, Bio-Path, Mateon, Genentech/Roche, Trovagene, AbbVie, Pfizer, Celgene, Imago, Astellas, Karyopharm, Seattle Genetics, and Incyte. D.A.P. receives research funding from Pfizer and Agios and served on advisory boards for Pfizer, Celyad, Agios, Celgene, AbbVie, Argenx, Takeda, and Servier. B.J.D. serves on the advisory boards for Aileron Therapeutics, Aptose, Blueprint Medicines, Cepheid, EnLiven Therapeutics, Gilead, GRAIL, Iterion Therapeutics, Nemucore Medical Innovations, the Novartis CML Molecular Monitoring Steering Committee, Recludix Pharma, the RUNX1 Research Program, ALLCRON Pharma, VB Therapeutics, Vincerx Pharma, and the Board of Directors for Amgen, and receives research funding from EnLiven and Recludix. B.J.D. is principal investigator or co-investigator on Novartis, BMS, and Pfizer clinical trials. His institution, OHSU, has contracts with these companies to pay for patient costs, nurse and data manager salaries, and institutional overhead, but he does not derive salary, nor does his laboratory receive funds, from these contracts. J.W.T. has received research support from Acerta, Agios, Aptose, Array, AstraZeneca, Constellation, Genentech, Gilead, Incyte, Janssen, Kronos, Meryx, Petra, Schrodinger, Seattle Genetics, Syros, Takeda, and Tolero and serves on the advisory board for Recludix Pharma. The authors certify that all compounds tested in this study were chosen without input from any of our industry partners. A subset of findings from this manuscript have been included in a pending patent application., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Carbon nanocages (CNCs), with unique merits of morphology and structure, have attracted increasing attention for energy storage and conversion. However, the synthesis of CNCs reported so far suffers from relatively harsh conditions and expensive raw materials. Herein, porous CNCs are intelligently designed using low-cost glucose as the carbon precursor via a facile K-functionalized carbon quantum dots (K-CQDs)-induced assembly route under hydrothermal process. The resulting CNCs have a unique cage-like structure, large surface area, and rich carboxyl groups. With these elegant structural merits, the as-made CNCs anode shows a high reversible capacity of 270 mAh g -1 at 100 mA g -1 after 200 cycles and a long-term cycling stability of 206 mAh g -1 at 2000 mA g -1 after 4000 cycles. An intercalation reaction mechanism with the K + intercalation compound is further identified through an in-situ Raman technique. Density functional theory simulations reveal that abundant carboxyl groups inherited from K-CQDs can significantly promote the potassium storage capacities of the CNCs electrode., (© 2022 Wiley-VCH GmbH.)

Despite high initial response rates, acute myeloid leukemia (AML) treated with the BCL-2-selective inhibitor venetoclax (VEN) alone or in combinations commonly acquires resistance. We performed gene/protein expression, metabolomic and methylation analyses of isogenic AML cell lines sensitive or resistant to VEN, and identified the activation of RAS/MAPK pathway, leading to increased stability and higher levels of MCL-1 protein, as a major acquired mechanism of VEN resistance. MCL-1 sustained survival and maintained mitochondrial respiration in VEN-RE cells, which had impaired electron transport chain (ETC) complex II activity, and MCL-1 silencing or pharmacologic inhibition restored VEN sensitivity. In support of the importance of RAS/MAPK activation, we found by single-cell DNA sequencing rapid clonal selection of RAS-mutated clones in AML patients treated with VEN-containing regimens. In summary, these findings establish RAS/MAPK/MCL-1 and mitochondrial fitness as key survival mechanisms of VEN-RE AML and provide the rationale for combinatorial strategies effectively targeting these pathways., (© 2022. The Author(s).)

Background: The role of fibulin-1 or FBLN1 in chondrocyte proliferation has not been reported so far. In this study, we aimed to verify whether FBLN1 promotes chondrocyte proliferation in elderly patients with knee osteoarthritis by phosphorylating Smad2., Methods: Chondrocytes were isolated from cartilage samples collected from elderly patients with osteoarthritis (n = 6) and young patients (n = 6). The isolated chondrocytes were divided into the following three groups: control (medium only); cells transfected with adenovirus expressing green fluorescent protein (Ad-GFP); and those transfected with adenovirus expressing green fluorescent protein and FBLN1 (Ad-GFP-FBLN1). Furthermore, chondrocytes were divided into the following three groups in the mechanistic analysis: group 1, medium only; group 2, Ad-FBLN1; and group 3, Ad-FBLN1+pSmad2 inhibitor. The cells were analyzed for the relevant indicators after culturing for 48 h., Results: There were more EdU-positive cells in the Ad-GFP-FBLN1 group than in the other two groups (both P < 0.05). Compared with the other two groups, the level of pSmad2 and Col2 in the Ad-GFP-FBLN1 group was significantly increased (P < 0.05). The gene expression level of each indicator was consistent with the protein expression level. There was no significant difference in the indicators between groups 1 and 3. The percentage of EdU-positive cells in group 2 was higher than that in the other two groups (P < 0.05). The expression of pSmad2 and Col2 in group 2 was higher than that in the other two groups (both P < 0.05)., Conclusion: FBLN1 can promote chondrocyte proliferation in the knee cartilage in elderly patients by phosphorylating Smad2., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest exists., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

To accelerate the commercial implementation of high-energy batteries, recent research thrusts have turned to the practicality of Si-based electrodes. Although numerous nanostructured Si-based materials with exceptional performance have been reported in the past 20 years, the practical development of high-energy Si-based batteries has been beset by the bias between industrial application with gravimetrical energy shortages and scientific research with volumetric limits. In this context, the microscale design of Si-based anodes with densified microstructure has been deemed as an impactful solution to tackle these critical issues. However, their large-scale application is plagued by inadequate cycling stability. In this review, we present the challenges in Si-based materials design and draw a realistic picture regarding practical electrode engineering. Critical appraisals of recent advances in microscale design of stable Si-based materials are presented, including interfacial tailoring of Si microscale electrode, surface modification of SiO x microscale electrode, and structural engineering of hierarchical microscale electrode. Thereafter, other practical metrics beyond active material are also explored, such as robust binder design, electrolyte exploration, prelithiation technology, and thick-electrode engineering. Finally, we provide a roadmap starting with material design and ending with the remaining challenges and integrated improvement strategies toward Si-based full cells.

Background: Slit diaphragm is a specialized adhesion junction between the opposing podocytes, establishing the final filtration barrier to urinary protein loss. At the cytoplasmic insertion site of each slit diaphragm there is an electron-dense and protein-rich cellular compartment that is essential for slit diaphragm integrity and signal transduction. Mutations in genes that encode components of this membrane-less compartment have been associated with glomerular diseases. However, the molecular mechanism governing formation of compartmentalized slit diaphragm assembly remains elusive., Methods: We systematically investigated the interactions between key components at slit diaphragm, such as MAGI2, Dendrin, and CD2AP, through a combination of biochemical, biophysical, and cell biologic approaches., Results: We demonstrated that MAGI2, a unique MAGUK family scaffold protein at slit diaphragm, can autonomously undergo liquid-liquid phase separation. Multivalent interactions among the MAGI2-Dendrin-CD2AP complex drive the formation of the highly dense slit diaphragm condensates at physiologic conditions. The reconstituted slit diaphragm condensates can effectively recruit Nephrin. A nephrotic syndrome-associated mutation of MAGI2 interfered with formation of the slit diaphragm condensates, thus leading to impaired enrichment of Nephrin., Conclusions: Key components at slit diaphragm ( e.g. , MAGI2 and its complex) can spontaneously undergo phase separation. The reconstituted slit diaphragm condensates can be enriched in adhesion molecules and cytoskeletal adaptor proteins. Therefore, the electron-dense slit diaphragm assembly might form via phase separation of core components of the slit diaphragm in podocytes., (Copyright © 2021 by the American Society of Nephrology.)

Two-dimensional (2D) metal oxides and chalcogenides (MOs & MCs) have been regarded as a new class of promising electro- and photocatalysts for many important chemical reactions such as hydrogen evolution reaction, CO 2 reduction reaction and N 2 reduction reaction in virtue of their outstanding physicochemical properties. However, pristine 2D MOs & MCs generally show the relatively poor catalytic performances due to the low electrical conductivity, few active sites and fast charge recombination. Therefore, considerable efforts have been devoted to engineering 2D MOs & MCs by rational structural design and chemical modification to further improve the catalytic activities. Herein, we comprehensively review the recent advances for engineering technologies of 2D MOs & MCs, which are mainly focused on the intercalation, doping, defects creation, facet design and compositing with functional materials. Meanwhile, the relationship between morphological, physicochemical, electronic, and optical properties of 2D MOs & MCs and their electro- and photocatalytic performances is also systematically discussed. Finally, we further give the prospect and challenge of the field and possible future research directions, aiming to inspire more research for achieving high-performance 2D MOs & MCs catalysts in energy storage and conversion fields., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.)

Circulating Tumor Cells (CTCs) are already present in the peripheral blood of patients with early tumors and even precancerous lesions. The objective of this study was to determine the count of CTCs in peripheral blood from high-risk population(HRP), healthy subjects and patients with Pan-cancer. The CTCs in the peripheral blood from HRP and cancer patients were enriched and identified based on the positive sorting method by epithelial cell adhesion molecular (EpCAM) liposome magnetic bead (Ep-LMB) and Vimentin liposome magnetic bead (Vi-LMB). Simultaneously, further analysis was carried out focusing on the clinical characteristics of patients by collecting the peripheral blood samples from healthy subjects as the parallel control. According to the results, the prepared LMBs had high specificity and stability, resulting in an average (Av) proliferation rate of over 90% for each cell line, and the average capture rate of higher than 80%. In terms of CTCs count detection in clinical blood samples, the average count was 0.9 (Ep: Av=0.6, Vi: Av=0.3), 2.4 (Ep: Av=1.4, Vi: Av=0.8) and 7.3 (Ep: Av=4.0, Vi: Av=3.3) in healthy subjects, HRP and total cancer patients, respectively. Besides, there was no obvious difference in the average count of CTCs among patients with different cancer types. While count of CTCs in the aforementioned cancer patients was statistically different from that in healthy subjects and patients with HRP. The survival time of cancer patients whose number of CTCs is greater than the average is significantly increased. Collectively, the study confirmed that CTCs can achieve early tumor detection and auxiliary diagnosis, and its number is related to the occurrence and development of tumors, and CTCs can be detected in HRP and sub-health population., Competing Interests: JZ, XL, XW and PS were employed by Huzhou Lieyuan Medical Laboratory Company Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Ding, Huang, Pan, Liu, Zhang, Zhou, Liang, Wang and Song.)

Metal-organic frameworks (MOFs) are important photocatalytic materials for H 2 production. To clarify the structure-function relationship and improve the photocatalytic activity, herein we explored a series of porphyrin-based zirconium MOFs (PCN-H 2 /Pt x : y , where x : y = 4:1, 3:2, 2:3, and 0:1) containing different ratios of H 2 TCPP and Pt II TCPP [TCPP = tetrakis(4-carboxyphenyl)porphyrinate] as isostructural ligands and Zr 6 clusters as nodes. Under visible-light irradiation, PCN-H 2 /Pt 0:1 shows the highest average H 2 evolution reaction rate (351.08 μmol h -1 g -1 ), which decreases along with lowering of the ratio of Pt II TCPP in the PCN-H 2 /Pt x : y series. The differences in photocatalytic activity are attributed to more uniformly dispersed Pt 2+ ions in PCN-H 2 /Pt 0:1 , which promotes charge transfer from porphyrins (photosensitizers) to Pt II ions (catalytic centers), leading to efficient charge separation in the MOF materials. The bifunctional MOFs with photosensitizers and catalytic centers provide new insight for the design and application of porphyrin-based photocatalytic systems for visible-light-driven H 2 production.

Background: Many non-drug interventions for decreasing non-specific chronic low back pain (NSCLBP) in nurses have been extensively studied, but the most effective approach is still unclear., Objective: This systematic review and network meta-analysis evaluated the efficacies of 12 non-drug interventions in reducing NSCLBP in nurses., Methods: PubMed, ScienceDirect, Web of Science, Cochrane, EMBASE, CINAHL, Medline, WANFANG, VIP, China Knowledge Integrated, and SinoMed were searched from their establishment to July 2019. Randomized controlled trials (RCTs) comparing non-drug interventions for NSCLBP in nurses were included and analyzed using Stata v15 statistical software., Results: A total of 31 RCTs (n= 7116) and 12 non-drug interventions were included. The first three results with the highest surface areas under the curve ranking area (SUCRAs) were low back exercise plus healthy education, single low back exercise, and yoga (SUCRAs: 79.4%, 76.2%, and 75.1%, respectively). In addition, single yoga was inferior to protective equipment (standardized mean difference [SMD] = 3.88, 95% confidence interval [CI]: 0.92 to 6.84) and multidisciplinary intervention (SMD =-4.06, 95% CI: -7.33 to -0.78)., Conclusions: Low back exercise plus health education may be the best approach to reduce NSCLBP in nurses. Considering the heterogeneity, our findings need to be confirmed in future multicenter large sample RCTs in different countries.

Background: Numerous studies have investigated factors for non-specific chronic low back pain (NSCLBP) in nurses, and have reached different conclusions. Evidence-based recommendations are required for the prevention and treatment of NSCLBP in nurses., Objective: This meta-analysis aimed to systematically review and quantify the factors of NSCLBP in nurses., Methods: Eleven databases were searched. The odds ratios (OR) with 95% confidence intervals (CIs) were pooled using meta-analysis, and either a fixed-effect or random-effect model was used based on heterogeneity across included studies., Results: Eighteen publications including 11,752 nursing staff were included. Being female (pooled estimate [95% CI], 1.56 [1.24-1.96]; P< 0.001), married (1.89 [1.38-2.60]; P< 0.001), overweight (0.63 [0.43-0.93]; P= 0.02), working at least 10 years (0.65 [0.48-0.89]; P= 0.007), and working night shifts (2.19 [1.16-4.21]; P= 0.02) were positively related to NSCLBP. Junior college education (0.60 [0.47-0.77]; P< 0.001) and job satisfaction (0.58 [0.47-0.73]; P< 0.001) were negatively related. Age (0.80 [0.50-1.27]; P= 0.34) and physical exercise (0.99 [0.39-2.49]; P= 0.98) were not related., Conclusions: This is the first meta-analysis to quantify the risk factors for NSCLBP in nurses. Being female, married, working night shifts, overweight, working at least 10 years and dissatisfied with work are risk factors. High-quality prospective studies are required to validate the findings of this study.

Purpose: The aim of the present study was to evaluate the expression of inflammasome and cytokine on experimental periodontitis with super activated platelet lysate (SPL) in rats., Methods: Periodontitis was induced by submerging cotton ligatures on the right side of the maxillary second molar in 36 Wistar rats. The rats were divided into 3 groups randomly: the rats received no treatment (control group); local injection with sterile saline (ligature+saline group) and local injection with SPL (ligature+SPL group). After treatments, the alveolar bone level and inflammation of periodontal tissue were evaluated by micro-computed tomography (micro-CT) scanning and histological examination, respectively. The expression of inflammasome and cytokine was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) assay., Results: Compared with the control group, the bone loss significantly increased by 0.9 mm in the ligature+saline group and 0.4 mm in the ligature+SPL group (P < 0.001). 0.5 mm reduction in the bone loss was founded in the ligature+SPL group compared with the ligature+saline group (P < 0.001). The gene expression of CCL2, CXCL2, IL-6, IL-18, IL-1α, IL-1β, CXCL10, CXCL16, CCL5 was significantly reduced in the ligature+SPL group compared with the ligature+saline group (P < 0.05). Compared with the ligature+saline group, the expression for inflammasome NLRP3, AIM2, CASP1 was both downregulated in the ligature+SPL group (P < 0.05)., Conclusion: Our present study demonstrated local injection of SPL regulated the expression of inflammasome and cytokine and had a visible effect of relieving inflammation in the experimental periodontitis in rats., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Zhang et al.)

Deregulation of the BCL2 gene family plays an important role in the pathogenesis of acute myeloid leukemia (AML). The BCL2 inhibitor, venetoclax, has received FDA approval for the treatment of AML. However, upfront and acquired drug resistance ensues due, in part, to the clinical and genetic heterogeneity of AML, highlighting the importance of identifying biomarkers to stratify patients onto the most effective therapies. By integrating clinical characteristics, exome and RNA sequencing, and inhibitor data from primary AML patient samples, we determined that myelomonocytic leukemia, upregulation of BCL2A1 and CLEC7A , as well as mutations of PTPN11 and KRAS conferred resistance to venetoclax and multiple venetoclax combinations. Venetoclax in combination with an MCL1 inhibitor AZD5991 induced synthetic lethality and circumvented venetoclax resistance.

Exploring Si-based anode materials with high electrical conductivity and electrode stability is crucial for high-performance lithium-ion batteries (LIBs). Herein, we propose the fabrication of a Si-based composite where Si porous nanospheres (Si p-NSs) are tightly wrapped by Ti 3 C 2 T x (T x stands for the surface groups such as -OH, -F) MXene nanosheets (TNSs) through an interfacial assembly strategy. The TNSs as a conductive and robust tight of the Si p-NSs can effectively improve electron transport and electrode stability, as revealed by substantial characterizations and mechanical simulations. Moreover, the TNSs with rich surface groups enable strong interfacial interactions with the Si p-NS component and a pseudocapacitive behavior, beneficial for fast and stable lithium storage. Consequently, the Si p-NS@TNSs electrode with a high Si content of 85.6% exhibits significantly enhanced battery performance compared with the Si p-NSs electrode such as high reversible capacity (1154 mAh g -1 at 0.2 A g -1 ), long cycling stability (up to 2000 cycles with a 0.026% capacity decay rate per cycle), and excellent rate performances. Notably, the Si p-NS@TNSs electrode-based LIB full cell delivers a high energy uptake of 405 Wh kg -1 , many-times higher than that of the Si p-NSs full cell. This work offers a strategy to develop advanced Si-based anode materials with desirable properties for high-performance LIBs.

Osteosarcoma (OS) is a primary malignant bone neoplasm with high frequencies of tumor metastasis and recurrence. Although the Akt/PKB signaling pathway is known to play key roles in tumorigenesis, the roles of cyclin-dependent kinase-like 3 (CDKL3) in OS progression remain largely elusive. We have demonstrated the high expression levels of CDKL3 in OS human specimens and comprehensively investigated the role of CDKL3 in promoting OS progression both in vitro and in vivo. We found that CDKL3 regulates Akt activation and its downstream effects, including cell growth and autophagy. The up-regulation of CDKL3 in OS specimens appeared to be associated with Akt activation and shorter overall patient survival ( P = 0.003). Our findings identify CDKL3 as a critical regulator that stimulates OS progression by enhancing Akt activation. CDKL3 represents both a biomarker for OS prognosis, and a potential therapeutic target in precision medicine by targeting CDKL3 to treat Akt hyper-activated OS., (© 2020 He et al.)

Three-dimensional (3D) cell cultures developed with living cells and scaffolds have demonstrated outstanding potential for tissue engineering and regenerative medicine applications. However, no suitable tools are available to monitor dynamically variable cell behavior in such a complex microenvironment. In particular, simultaneously assessing cell behavior, cell secretion, and the general state of a 3D culture system is of a really challenging task. This paper presents our development of a dual-transduction-integrated biosensing system that assesses electrical impedance in conjunction with imaging techniques to simultaneously investigate the 3D cell-culture for bone regeneration. First, we created models to mimic the dynamic deposition of the extracellular matrix (ECM) in 3D culture, which underwent osteogenesis by incorporating different amounts of bone-ECM components (collagen, hydroxyapatite [HAp], and hyaluronic acid [HA]) into alginate-based hydrogels. The formed models were investigated by means of electrical impedance spectroscopy (EIS), with the results showing that the impedances increased linearly with collagen and hyaluronan, but changed in a more complex manner with HAp. Thereafter, we created two models that consisted of primary osteoblast cells (OBs), which expressed the enhanced green fluorescent protein (EGFP), and 4T1 cells, which secreted the EGFP-HA, in the alginate hydrogel. We found the capacitance (associated with impedance and measured by EIS) increased with the increases in initial embedded OBs, and also confirmed the cell proliferation over 3 days with the EGFP signal as monitored by the fluorescent imaging component in our system. Interestingly, the change in capacitance is found to be associated with OB migration following stimulation. Also, we show higher capacitance in 4T1 cells that secret HA when compared to control 4T1 cells after a 3-day culture. Taken together, we demonstrate that our biosensing system is able to investigate the dynamic process of 3D culture in a non-invasive and real-time manner., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities., (© 2019 by The American Society of Hematology.)

The interfacial engineering plays an important role in enhancing the electrochemical properties of graphene-based hybrid materials for energy conversion and storage. Herein, we propose a facile interfacial engineering route for achieving a novel type of SnS 2 /N-doped graphene (SnS 2 /NG) composite with superior lithium storage capability. Interestingly, the SnS 2 particles formed show two totally different morphologies including ultrasmall nanoparticles about 5 nm and ultrathin nanosheets, and they are strongly coupled with nitrogen-doped graphene, giving rise to a unique 0D/2D heterostructure. In the process, the multiple roles of the 3-aminophenol (AP) linker are well identified by combining the experimental results with the theoretical calculations, where a strong interface is successfully constructed between SnS 2 and functionalized graphene. The electrochemical test results demonstrate that the as-made SnS 2 /NG composite exhibits a high lithium storage capacity (1101.3 mAh g -1 at 100 mA g -1 ), superior cycling stability (a capability fading of 0.04% per cycle for 200 cycles at 100 mA g -1 ), as well as a good rate retention. Such a unique hierarchical nanostructure and the strong interfacial interaction between 0D/2D SnS 2 and nitrogen-doped graphene highlight the lithium storage performance of SnS 2 /NG., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this study, a nonlinear analysis method called improved information entropy (IIE) is proposed on the basis of constructing a special probability mass function for the normalized analysis of Shannon entropy for a time series. The definition is directly applied to several typical time series, and the characteristic of IIE is analyzed. This method can distinguish different kinds of signals and reflects the complexity of one-dimensional time series of high sensitivity to the changes in signal. Thus, the method is applied to the fault diagnosis of a rolling bearing. Experimental results show that the method can effectively extract the sensitive characteristics of the bearing running state and has fast operation time and minimal parameter requirements.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.

Genetic rearrangements involving FLT3 are rare and only recently have been detected in myeloid/lymphoid neoplasms associated with eosinophilia (MLN-eos) and chronic myeloproliferative disorders. Here we report two cases with FLT3 fusions in patients demonstrating mixed features of myelodysplastic/myeloproliferative neoplasms. In the first case, FLT3 was fused with a new fusion partner MYO18A in a patient with marrow features most consistent with atypical chronic myeloid leukemia; the second case involving ETV6 - FLT3 fusion was observed in a case with bone marrow features most consistent with chronic myelomonocytic leukemia. Notably, we observed that samples from both patients demonstrated FLT3 inhibitor (quizartinib and sorafenib) sensitivity in ex vivo drug screening assay., (© 2018 Zhang et al.; Published by Cold Spring Harbor Laboratory Press.)

It has been widely reported that "naked" gold nanoparticles (Au NPs) without protectors have glucose oxidase (GOx)-like activity, and the use of protectors can inhibit the GOx-like activity. Here, "non-naked" Au NPs with GOx-like activity are synthesized by using protein as protector. Although "naked" Au NPs have peroxidase-like activity and GOx-like activity, the optimal pH ranges of the both activities are obviously different. Fortunately, as-synthesized "non-naked" Au NPs show the dual enzyme-like activities at the same pH. So, "non-naked" Au NPs can be described as "tandem nanozyme." As another bonus, the participation of protein protector can stabilize the GOx-like activity and make Au NPs modifiable. Even though Au NPs are connected with graphene oxide (GO), the GOx-like activity is still not changed. Further, Au NPs-GO nanocomposites are applied on the one-pot nonenzymatic glucose colorimetric detection. The "non-naked" gold not only broadens the species of tandem nanozymes, but also facilitates the functionalization of nanozymes, which is promising for immunoassay, biosensor, and medical treatment., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.

Layered material MoS 2 is widely applied as a promising anode for lithium-ion batteries (LIBs). Herein, a scalable and facile dopamine-assisted hydrothermal technique for the preparation of strongly coupled MoS 2 nanosheets and nitrogen-doped graphene (MoS 2 /N-G) composite is developed. In this composite, the interconnected MoS 2 nanosheets are well wrapped onto the surface of graphene, forming a unique veil-like architecture. Experimental results indicate that dopamine plays multiple roles in the synthesis: a binding agent to anchor and uniformly disperse MoS 2 nanosheets, a morphology promoter, and the precursor for in situ nitrogen doping during the self-polymerization process. Density functional theory calculations further reveal that a strong interaction exists at the interface of MoS 2 nanosheets and nitrogen-doped graphene, which facilitates the charge transfer in the hybrid system. When used as the anode for LIBs, the resulting MoS 2 /N-G composite electrode exhibits much higher and more stable Li-ion storage capacity (e.g., 1102 mAh g -1 at 100 mA g -1 ) than that of MoS 2 /G electrode without employing the dopamine linker. Significantly, it is also identified that the thin MoS 2 nanosheets display outstanding high-rate capability due to surface-dominated pseudocapacitance contribution., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Granulocyte colony-stimulating factor (G-CSF or CSF3) and its receptor CSF3R regulate granulopoiesis, neutrophil function, and hematopoietic stem cell mobilization. Recent studies have uncovered an oncogenic role of mutations in the CSF3R gene in many hematologic malignancies. To find additional CSF3R mutations that give rise to cell transformation, we performed a cellular transformation assay in which murine interleukin 3 (IL-3)-dependent Ba/F3 cells were transduced with WT CSF3R plasmid and screened for spontaneous growth in the absence of IL-3. Any outgrowth clones were sequenced to identify CSF3R mutations with transformation capacity. We identified several novel mutations and determined that they transform cells via four distinct mechanisms: 1) cysteine- and disulfide bond-mediated dimerization (S581C); 2) polar, noncharged amino acid substitution at the transmembrane helix dimer interface at residue Thr-640; 3) increased internalization by a Glu-524 substitution that mimics a low G-CSF dose; and 4) hydrophobic amino acid substitutions in the membrane-proximal residues Thr-612, Thr-615, and Thr-618. Furthermore, the change in signaling activation was related to an altered CSF3R localization. We also found that CSF3R-induced STAT3 and ERK activations require CSF3R internalization, whereas STAT5 activation occurred at the cell surface. Cumulatively, we have expanded the regions of the CSF3R extracellular and transmembrane domains in which missense mutations exhibit leukemogenic capacity and have further elucidated the mechanistic underpinnings that underlie altered CSF3R expression, dimerization, and signaling activation., (© 2018 Zhang et al.)

In the work, small TiO2 porous nanoparticles with an average size of 60 nm have been prepared by a simple, eco-friendly, and one-step hydrothermal method. The TiO2 products are achieved by only using tetrabutyl titanate (TBOT), tetrapropylammonium hydroxide (TPAOH), and water as the starting materials. Various techniques such as SEM, TEM, HRTEM, XRD, Raman, and BET are used to characterize the surface morphology and structural features of products. The growth parameters including reaction time, titanium source and temperature of thermal treatment are systematically investigated. In the synthesis, TPAOH plays a decisive role as structure-directing agent for the formation of desirable TiO2 nanostructure. The photocatalytic tests manifest that the TiO2 nanoparticles annealed at 450 °C shows an outstanding photocatalytic activity for degradation of methyl orange (MO) and rhodamine B (RhB), which is comparable to Degussa P25. The superior performance may mainly come from the contributions of their small particle size and unique nanostructure.