Porous hybrid encapsulation enables high-rate lithium storage for a micron-sized SiO anode.

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.

Upregulation of HOXA3 by isoform-specific Wilms tumour 1 drives chemotherapy resistance in acute myeloid leukaemia.

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.

A prognostic nomogram integrating carcinoembryonic antigen levels for predicting overall survival in elderly patients with stage II-III colorectal cancer.

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.

Impact of varied immunosuppressive agents and post-transplant diabetes mellitus on prognosis among diverse transplant recipients (experimental studies).

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.

High-Rate SiO Lithium-Ion Battery Anode Enabled by Rationally Interfacial Hybrid Encapsulation Engineering.

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, Ti3C2Tx 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 Ti3C2Tx 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 Li2O 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.

FEN1 Promotes Hepatocellular Carcinoma Progression by Activating Cell Cycle Transition from G2 To M Phase.

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.

Chromosome-level genome assembly of sea scallop Placopecten magellanicus provides insights into the genetic characteristics and adaptive evolution of large scallops.

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.

Emerging Multiscale Porous Anodes toward Fast Charging Lithium-Ion Batteries.

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.

USP10 strikes down ß-catenin by dual-wielding deubiquitinase activity and phase separation potential.

Wnt/ß-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 ß-catenin. Mechanistically, USP10 binds to key scaffold Axin1 via conserved motifs and stabilizes Axin1 through K48-linked deubiquitination. Surprisingly, USP10 physically tethers Axin1 and ß-catenin and promotes the phase separation for ß-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 ß-catenin. In colorectal cancer, USP10 substantially represses cancer growth mainly through physical promotion of phase separation and correlates with Wnt/ß-catenin magnitude clinically. Collectively, we discovered USP10 functioning in multiple biological processes against ß-catenin and unearthed the enzyme-dependent and -independent "dual-regulating" mechanism. These two functions of USP10 work in parallel and are context dependent.

Effect of five-elements music therapy combined with Baduanjin qigong on patients with mild COVID-19.

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.

High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist.

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.

Oxygenated Triazine-Heptazine Heterostructure Creates an Enormous Ascension to the Visible Light Photocatalytic Hydrogen Evolution Performance of Porous C3 N4 Nanosheets.

A highly efficient g-C3 N4 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-C3 N4 . 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-C3 N4 .

Circular RNA circDOCK1 contributes to osteosarcoma progression by acting as a ceRNA for miR-936 to regulate LEF1.

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_circ_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.

Aberrant Cholesterol Metabolism and Wnt/ß-Catenin Signaling Coalesce via Frizzled5 in Supporting Cancer Growth.

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/ß-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.

A cascade amplification strategy for ultrasensitive Salmonella typhimurium detection based on DNA walker coupling with CRISPR-Cas12a.

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.

K-Functionalized Carbon Quantum Dots-Induced Interface Assembly of Carbon Nanocages for Ultrastable Potassium Storage Performance.

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.

Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia.

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.