TabDEG: Classifying differentially expressed genes from RNA-seq data based on feature extraction and deep learning framework.

Traditional differential expression genes (DEGs) identification models have limitations in small sample size datasets because they require meeting distribution assumptions, otherwise resulting high false positive/negative rates due to sample variation. In contrast, tabular data model based on deep learning (DL) frameworks do not need to consider the data distribution types and sample variation. However, applying DL to RNA-Seq data is still a challenge due to the lack of proper labeling and the small sample size compared to the number of genes. Data augmentation (DA) extracts data features using different methods and procedures, which can significantly increase complementary pseudo-values from limited data without significant additional cost. Based on this, we combine DA and DL framework-based tabular data model, propose a model TabDEG, to predict DEGs and their up-regulation/down-regulation directions from gene expression data obtained from the Cancer Genome Atlas database. Compared to five counterpart methods, TabDEG has high sensitivity and low misclassification rates. Experiment shows that TabDEG is robust and effective in enhancing data features to facilitate classification of high-dimensional small sample size datasets and validates that TabDEG-predicted DEGs are mapped to important gene ontology terms and pathways associated with cancer.

Molecular recognition with resolution below 0.2 angstroms through thermoregulatory oscillations in covalent organic frameworks.

Crystalline materials with uniform molecular-sized pores are desirable for a broad range of applications, such as sensors, catalysis, and separations. However, it is challenging to tune the pore size of a single material continuously and to reversibly distinguish small molecules (below 4 angstroms). We synthesized a series of ionic covalent organic frameworks using a tetraphenoxyborate linkage that maintains meticulous synergy between structural rigidity and local flexibility to achieve continuous and reversible (100 thermal cycles) tunability of "dynamic pores" between 2.9 and 4.0 angstroms, with resolution below 0.2 angstroms. This results from temperature-regulated, gradual amplitude change of high-frequency linker oscillations. These thermoelastic apertures selectively block larger molecules over marginally smaller ones, demonstrating size-based molecular recognition and the potential for separating challenging gas mixtures such as oxygen/nitrogen and nitrogen/methane.

Covalent Organic Framework-based Solid-State Electrolytes, Electrode Materials, and Separators for Lithium-ion Batteries.

The increasing global energy consumption has led to the rapid development of renewable energy storage technologies. Lithium-ion batteries (LIBs) have been extensively studied and utilized for reliable, efficient, and sustainable energy storage. Nevertheless, designing new materials for LIB applications with high capacity and long-term stability is highly desired but remains a challenging task. Recently, covalent organic frameworks (COFs) have emerged as superior candidates for LIB applications due to their high porosity, well-defined pores, highly customizable structure, and tunable functionalities. These merits enable the preparation of tailored COFs with predesigned redox-active moieties and suitable porous channels that can improve the lithium-ion storage and transportation. This review summarizes the recent progress in the development of COFs and their composites for a variety of LIB applications, including (quasi) solid-state electrolytes, electrode materials, and separators. Finally, the challenges and potential future directions of employing COFs for LIBs are also briefly discussed, further promoting the foundation of this class of exciting materials for future advances in energy-related applications.

Peripheral T-cell subsets in radiofrequency ablation for tumors from different origins.

BACKGROUNDS: Radiofrequency ablation (RFA) is known to destroy tumoral tissue and activate immune cells. This study aimed to investigate the impact of RFA on peripheral T-cell responses and its relationship with tumor origin and hepatitis status. METHODS: A retrospective analysis was conducted on 62 patients with various types of tumors, including hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, and others, who underwent RFA treatment between June 2017 and December 2018. Blood samples were collected before and one day after RFA treatment. The peripheral T-cell subsets were measured by flow cytometry, and their changes were analyzed. RESULTS: The study found a decrease in the CD4+CD8-and CD4-CD8+ T-cell subsets after RFA, but no significant changes were observed in the populations of CD4+CD8+ and the CD4+CD8-/CD4-CD8+ ratio. Furthermore, no significant differences were observed in peripheral T-cell subsets concerning tumor type or hepatitis status. CONCLUSIONS: The study suggests that RFA treatment may have a short-term impact on peripheral T-cell responses, characterized by a decrease in certain T-cell subsets. However, these changes do not seem to be related to the tumor type or hepatitis status of the patients.

Single-crystal polymers (SCPs): from 1D to 3D architectures.

Single-crystal polymers (SCPs) with unambiguous chemical structures at atomic-level resolutions have attracted great attention. Obtaining precise structural information of these materials is critical as it enables a deeper understanding of the potential driving forces for specific packing and long-range order, secondary interactions, and kinetic and thermodynamic factors. Such information can ultimately lead to success in controlling the synthesis or engineering of their crystal structures for targeted applications, which could have far-reaching impact. Successful synthesis of SCPs with atomic level control of the structures, especially for those with 2D and 3D architectures, is rare. In this review, we summarize the recent progress in the synthesis of SCPs, including 1D, 2D, and 3D architectures. Solution synthesis, topochemical synthesis, and extreme condition synthesis are summarized and compared. Around 70 examples of SCPs with unambiguous structure information are presented, and their synthesis methods and structural analysis are discussed. This review offers critical insights into the structure-property relationships, providing guidance for the future rational design and bottom-up synthesis of a variety of highly ordered polymers with unprecedented functions and properties.

Effects of the Fear of COVID-19 and Efficacy of Coping Behavior for Infectious Diseases after the End of COVID-19: Moderating Effects of Cyberchondria and eHealth Literacy.

As the coronavirus disease (COVID-19) pandemic ends, it is worth considering whether the ability to cope with such a pandemic has improved. The initial response to COVID-19 was hampered by the fear of new infectious diseases and spread of misinformation on the Internet. This highlights the need to enhance our ability to critically evaluate information rather than indiscriminately search for and trust information on the Internet. Therefore, this study examined how cyberchondria and eHealth literacy moderate the effect of fear of COVID-19 on the efficacy of coping behaviors for future epidemics and pandemics. The participants were 1000 adults in South Korea who were selected based on population proportionality. The results showed that fear of COVID-19 was significantly positively related to cyberchondria, and eHealth literacy was significantly positively related to the efficacy of coping behaviors. Further, the fear of COVID-19 had a significantly negative effect on the efficacy of coping behaviors, and the moderating effect of cyberchondria varied according to the level of eHealth literacy. These results emphasize the importance of eHealth literacy in enabling critical decision-making regarding misinformation.

3D Covalent Organic Framework as a Metastable Intermediate in the Formation of a Double-Stranded Helical Covalent Polymer.

The design and development of intricate artificial architectures have been pursued for decades. Helical covalent polymer (HCP) was recently reported as an unexpected topology that consists of chiral 1D polymers assembled through weak hydrogen bonds from achiral building blocks. However, many questions remained about the formation, driving force, and the single-handedness observed in each crystal. In this work, we reveal a metastable, racemic, fully covalently cross-linked, 3D covalent organic framework (COF) as an intermediate in the early stage of polymerization, which slowly converts into single-handed HCP double helices through partial fragmentation and self-sorting with the aid of a series of hydrogen bonding. Our work provides an intriguing example where weak noncovalent bonds serve as the determining factor of the overall product structure and facilitate the formation of a sophisticated polymeric architecture.

Reprocessible Triketoenamine-Based Vitrimers with Closed-Loop Recyclability.

Development of thermosets that can be repeatedly recycled via both chemical route (closed-loop) and thermo-mechanical process is attractive and remains an imperative task. In this work, we reported a triketoenamine based dynamic covalent network derived from 2,4,6-triformylphloroglucinol and secondary amines. The resulting triketoenamine based network does not have intramolecular hydrogen bonds, thus reducing its π-electron delocalization, lowering the stability of the tautomer structure, and enabling its dynamic feature. By virtue of the highly reversible bond exchange, this novel dynamic covalent bond enables the easy construction of highly crosslinked and chemically reprocessable networks from commercially available monomers. The as-made polymer monoliths exhibit high mechanical properties (tensile strength of 79.4 MPa and Young's modulus of 571.4 MPa) and can undergo a monomer-network-monomer (yields up to 90 %) recycling mediated by an aqueous solution, with the new-generation polymer capable of restoring the material strength to its original state. In addition, owing to its dynamic nature, a catalyst-free and low-temperature reprogrammable covalent adaptable network (vitrimer) was achieved. The design concept reported herein can be applied to the development of other novel vitrimers with high repressibility and recyclability, and sheds light on future design of sustainable polymers with minimal environmental impact.

Dynamic Covalent Self-sorting in Molecular and Polymeric Architectures Enabled by Spiroborate Bond Exchange.

Self-sorting is commonly observed in complex reaction systems, which has been utilized to guide the formation of single major by-design molecules. However, most studies have been focused on non-covalent systems, and using self-sorting to achieve covalently bonded architectures is still relatively less explored. Herein, we first demonstrated the dynamic nature of spiroborate linkage and systematically studied the self-sorting behavior observed in the transformation between spiroborate-linked well-defined polymeric and molecular architectures, which is enabled by spiroborate bond exchange. The scrambling between a macrocycle and a 1D helical covalent polymer led to the formation of a molecular cage, whose structures are all unambiguously elucidated by single-crystal X-ray diffraction. The results indicate that the molecular cage is the thermodynamically favored product in this multi-component reaction system. This work represents the first example of a 1D polymeric architecture transforming into a shape-persistent molecular cage, driven by dynamic covalent self-sorting. This study will further guide the design of spiroborate-based materials and open the possibilities for the development of novel complex yet responsive dynamic covalent molecular or polymeric systems.

Spiroborate-Linked Ionic Covalent Adaptable Networks with Rapid Reprocessability and Closed-Loop Recyclability.

Covalent adaptable networks (CANs) represent a novel class of polymeric materials crosslinked by dynamic covalent bonds. Since their first discovery, CANs have attracted great attention due to their high mechanical strength and stability like conventional thermosets under service conditions and easy reprocessability like thermoplastics under certain external stimuli. Here, we report the first example of ionic covalent adaptable networks (ICANs), a type of crosslinked ionomers, consisting of negatively charged backbone structures. More specifically, two ICANs with different backbone compositions were prepared through spiroborate chemistry. Given the dynamic nature of the spiroborate linkages, the resulting ionomer thermosets display rapid reprocessability and closed-loop recyclability under mild conditions. The materials mechanically broken into smaller pieces can be reprocessed into coherent solids at 120 °C within only 1 min with nearly 100% recovery of the mechanical properties. Upon treating the ICANs with dilute hydrochloric acid at room temperature, the valuable monomers can be easily chemically recycled in almost quantitative yield. This work demonstrates the great potential of spiroborate bonds as a novel dynamic ionic linkage for development of new reprocessable and recyclable ionomer thermosets.

Carbazolylene-Ethynylene Macrocycle based Conductive Covalent Organic Frameworks.

Two covalent organic frameworks consisting of carbazolylene-ethynylene shape-persistent macrocycles with azine (MC-COF-1) or imine (MC-COF-2) linkages were synthesized via imine condensation. The obtained 2D frameworks are fully conjugated which imparts semiconducting properties. In addition, the frameworks showed high porosity with aligned accessible porous channels along the z axis, serving as an ideal platform for post-synthetic incorporation of I2 into the channels to enable electrical conductivity. The resulting MC-COF-1 showed an electrical conductivity up to 7.8×10-4  S cm-1 at room temperature upon I2 doping with the activation energy as low as 0.09 eV. Furthermore, we demonstrated that the electrical properties of both MC-COFs are switchable between electron-conducting and insulating states by simply implementing doping-regenerating cycles. The knowledge gained in this study opens new possibilities for the future development of tunable conductive 2D organic materials.

Flocking Behaviors under Hierarchical Leadership of Thermodynamic Cucker-Smale Particles with Multiplicative White Noise and Perturbation.

The thermodynamic Cucker-Smale model (TCS model) describes dynamic consistency caused by different temperatures between multi-agent particles. This paper studies the flocking behaviors of the TCS model with multiplicative white noise under hierarchical leadership. First, we introduce the corresponding model of two particles. Then, by using mathematical induction and considering the properties of differential functions, it is proved that, under certain conditions, the group can achieve flocking. Finally, we verify the conclusion through numerical simulation results. Similarly, this paper studies the above model with perturbation functions.

Strong and Tough Supramolecular Covalent Adaptable Networks with Room-Temperature Closed-Loop Recyclability.

Development of closed-loop chemically recyclable plastics (CCRPs) that can be widely used in daily life can be a fundamental solution to the global plastic waste crisis. Hence, it is of great significance to develop easy-to-recycle CCRPs that possess superior or comparable material properties to the commodity plastics. Here, a novel dual crosslinked CCRP, namely, supramolecular covalent adaptable networks (supra-CANs), is reported, which not only displays mechanical properties higher than the strong and tough commodity polycarbonate, but also exhibits excellent solvent resistance as thermosets. The supra-CANs are constructed by introducing reversible noncovalent crosslinks into the dynamic covalent polymer networks, resulting in highly stiff and strong thermosets that also exhibit thermoplastic-like ductile and tough behaviors as well as reprocessability and rehealability. In great contrast, the analogs that do not have noncovalent crosslinks (CANs) show elastomeric properties with significantly decreased mechanical strength. Importantly, the developed supra-CANs and CANs can be converted back into the initial monomers in high yields and purity at room temperature, even with additives, which enables the sustainable polymer-monomer-polymer circulation. This work provides new design principles for high-performance chemically recyclable polymers as sustainable substitutes for the conventional plastics.

Recyclable and malleable thermosets enabled by activating dormant dynamic linkages.

Chemical recycling of polymers is critical for improving the circular economy of plastics and environmental sustainability. Traditional thermoset polymers have generally been considered permanently crosslinked materials that are difficult or impossible to recycle. Herein, we demonstrate that by activating 'dormant' covalent bonds, traditional polycyanurate thermosets can be recycled into the original monomers, which can be circularly reused for their original purpose. Through retrosynthetic analysis, we redirected the synthetic route from forming conventional C-N bonds via irreversible cyanate trimerization to forming the C-O bonds through reversible nucleophilic aromatic substitution of alkoxy-substituted triazine derivatives by alcohol nucleophiles. The new reversible synthetic route enabled the synthesis of previously inaccessible alkyl-polycyanurate thermosets, which exhibit excellent film properties with high chemical resistance, closed-loop recyclability and reprocessing capability. These results show that 'apparently dormant' dynamic linkages can be activated and utilized to construct fully recyclable thermoset polymers with a broader monomer scope and increased sustainability.

Cyanurate-Linked Covalent Organic Frameworks Enabled by Dynamic Nucleophilic Aromatic Substitution.

We report, for the first time, highly crystalline cyanurate-linked covalent organic frameworks synthesized via dynamic nucleophilic aromatic substitution. The high crystallinity is enabled by the bond exchange reaction (self-correction) between 2,4,6-triphenoxy-1,3,5-triazine and diphenols via reversible SNAr catalyzed by triazabicyclodecene. The CN-COFs contain flexible backbones that exhibit a unique AA'-stacking due to interlayer hydrogen bonding interactions. The isoreticular expansion study demonstrates the general applicability of this synthetic method. The resulting CN-COFs exhibited good stability, as well as high CO2/N2 selectivity.

Integrative network pharmacology and experimental verification to reveal the anti-inflammatory mechanism of ginsenoside Rh4.

Inflammation is an innate immune response to infection, and it is the main factor causing bodily injury and other complications in the pathological process. Ginsenoside Rh4 (G-Rh4), a minor ginsenoside of Panax ginseng C. A. Meyer and Panax notoginseng, has excellent pharmacological properties. However, many of its major pharmacological mechanisms, including anti-inflammatory actions, remain unrevealed. In this study, network pharmacology and an experimental approach were employed to elucidate the drug target and pathways of G-Rh4 in treating inflammation. The potential targets of G-Rh4 were selected from the multi-source databases, and 58 overlapping gene symbols related to G-Rh4 and inflammation were obtained for generating a protein-protein interaction (PPI) network. Molecular docking revealed the high affinities between key proteins and G-Rh4. Gene ontology (GO) and pathway enrichment analyses were used to analyze the screened core targets and explore the target-pathway networks. It was found that the JAK-STAT signaling pathway, TNF signaling pathway, NF-κB signaling pathway, and PI3K-Akt signaling pathway may be the key and main pathways of G-Rh4 to treat inflammation. Additionally, the potential molecular mechanisms of G-Rh4 predicted from network pharmacology analysis were validated in RAW264.7 cells. RT-PCR, Western blot, and ELISA analysis indicated that G-Rh4 significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, as well as inflammation-related enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, in vitro experiments evaluated that Ginsenoside Rh4 exerts anti-inflammatory effects via the NF-κB and STAT3 signaling pathways. It is believed that our study will provide the basic scientific evidence that G-Rh4 has potential anti-inflammatory effects for further clinical studies.

Cage-Confinement Induced Emission Enhancement.

As a proof-of-concept study, Imi-cage and Phos-cage organic molecular cages (OMCs) containing the triphenylphosphine (TPP) moiety, a nonclassic AIE luminogen (AIEgen), have been designed to demonstrate the cage-confinement induced emission enhancement (CCIEE). Thanks to the confinement effect of OMCs, the rigid Imi-cage exhibits much higher photoluminescence (PL) quantum yield (ΦPL) than the open-shell Semicage and small molecule TPP in both solution and amorphous solid states. The emission of Phos-cage could be further enhanced in crystalline solid state with a remarkably high ΦPL of 97.6% (vs 3.47% of crystalline TPP) benefiting from AIE enabled by the highly ordered molecular packing. The novel strategy of CCIEE via confining an AIEgen into an OMC to achieve a significant emission enhancement will shed light on the development of solid-state highly fluorescent materials. The fluorescent nature of Imi-cage was further exploited for the ultrahighly sensitive detection of the explosive picric acid.

Effects of exogenous N and endogenous nutrients on alpine tundra litter decomposition in an area of high nitrogen deposition.

The effects of N deposition on the C and N cycles via altered litter decomposition rates are an important aspect of global environmental change. The Changbai Mountain region experienced a high N deposition (2.7 g·m-2·year-1 in 2015) and corresponding expansion of Deyeuxia purpurea into the alpine tundra, resulting in changes in endogenous nutrients. However, the relative contributions of the N deposition and endogenous litter nutrients to litter decompositions remain unclear. Therefore, a 5-year N addition and 2-year litter decomposition experiments were conducted. Exogenous N reduced the remaining litter mass of Rhododendron aureum at the early stage (30-240 d) by promoting soluble sugar release, and increased it at the late stage (360-720 d) by suppressing lignin release and decreasing soil microbial community and enzyme activity. A higher proportion of D. purpurea litter (representing higher N, lower lignin, and C:N ratio) decreased remaining litter mass and increased net N release. Exogenous N decreased decomposition rate from 0.32 to 0.21 and net N release from 34% to 24%, whereas litter compositions increased decomposition rates from 0.32 to 0.69 and net litter N release from 34% to 69%. Endogenous litter nutrients directly explained 62% and 40% of the litter decomposition and net N release variables, respectively, whereas exogenous N indirectly explained 12% and 9%, respectively. Thus, we infer that the reductions in C and N storage following D. purpurea expansion may offset the increases of C and N storage under N deposition and the expansion of D. purpurea has a potential long-term negative impact on the ability of tundra plants to sequester C and N in the alpine tundra of the Changbai Mountains. These findings highlight how shifting plant expansion, through changes endogenous nutrients, can influence tundra litter decomposition and C and N storage responses to N deposition.

Sonodynamic Effects of a Novel Ether-Group Modified Porphyrin Derivative Combined With Pulsed Low-Intensity Ultrasound on PC-9 Cells.

Sonodynamic therapy (SDT) is a developing modality for cancer treatment based on the synergistic effect of ultrasound and chemical compounds which are known as sonosensitizers. The development of more efficient sonosensitizers has become an urgent issue in this field. In this study, a novel porphyrin derivative (BBTPP) mediated SDT was evaluated on PC-9 cells. Pulsed low-intensity ultrasound (PLIU) was used for its little thermal and mechanical damage. The accumulation of drugs in cells was evaluated through porphyrin fluorescence, and the cytotoxicity of BBTPP was evaluated using a cell counting kit-8 assay. The sonodynamic effect was investigated by Hoechst 33342/PI and Annexin V-FITC/PI double staining, which showed an apoptotic rate of 18.87% in the BBTPP-SDT group, as compared with 1.71%, 1.4%, 1.57%, 3.61%, 11.18% in the control, BBTPP, hematoporphyrin monomethyl ether (HMME), ultrasound, and HMME-SDT groups, respectively. The sono-toxic effect of BBTPP was significantly superior to HMME. Our results showed that BBTPP-SDT resulted in much higher intracellular reactive oxygen species (ROS) and lipid peroxidation levels which were evaluated by 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) and Liperfluo assay, respectively. The expressions of Bax, Bcl-2, caspase-9, caspase-8, and cleaved caspase-3 proteins were evaluated to investigate the apoptotic mechanism of BBTPP-SDT. The results of this study showed that the combination of BBTPP and PLIU induced the generation of ROS, resulting in lipid peroxidation, and activated both the extrinsic and intrinsic apoptotic pathways of PC-9 cells. Our results also suggested that the ether group introduced in the side chain of porphyrin could enhance the sono-toxicity of porphyrin-based sensitizers under the sonication of PLIU. These results supported the possibility of BBTPP as a promising sonosensitizer, and an appropriate side chain could enhance the sono-sensitivity of porphyrins.

(20S) Ginsenoside Rh2 Exerts Its Anti-Tumor Effect by Disrupting the HSP90A-Cdc37 System in Human Liver Cancer Cells.

(20S) ginsenoside Rh2 (G-Rh2), a major bioactive metabolite of ginseng, effectively inhibits the survival and proliferation of human liver cancer cells. However, its molecular targets and working mechanism remain largely unknown. Excitingly, we screened out heat shock protein 90 alpha (HSP90A), a key regulatory protein associated with liver cancer, as a potential target of (20S) G-Rh2 by phage display analysis and mass spectrometry. The molecular docking and thermal shift analyses demonstrated that (20S) G-Rh2 directly bound to HSP90A, and this binding was confirmed to inhibit the interaction between HSP90A and its co-chaperone, cell division cycle control protein 37 (Cdc37). It is well-known that the HSP90A-Cdc37 system aids in the folding and maturation of cyclin-dependent kinases (CDKs). As expected, CDK4 and CDK6, the two G0-G1 phase promoting kinases as well as CDK2, a key G1-S phase transition promoting kinase, were significantly downregulated with (20S) G-Rh2 treatment, and these downregulations were mediated by the proteasome pathway. In the same condition, the cell cycle was arrested at the G0-G1 phase and cell growth was inhibited significantly by (20S) G-Rh2 treatment. Taken together, this study for the first time reveals that (20S) G-Rh2 exerts its anti-tumor effect by targeting HSP90A and consequently disturbing the HSP90A-Cdc37 chaperone system. HSP90A is frequently overexpressed in human hepatoma cells and the higher expression is closely correlated to the poor prognosis of liver cancer patients. Thus, (20S) G-Rh2 might become a promising alternative drug for liver cancer therapy.