Constructing N-Containing Poly(p-Phenylene) (PPP) Films Through A Cathodic-Dehalogenation Polymerization Method.

Developing the films of N-containing unsubstituted poly(p-phenylene) (PPP) films for diverse applications is significant and highly desirable because the replacement of sp2 C atoms with sp2 N atoms will bring novel properties to the as-prepared polymers. In this research, an electrochemical-dehalogenation polymerization strategy is employed to construct two N-containing PPP films under constant potentials, where 2,5-diiodopyridine (DIPy) and 2,5-dibromopyrazine (DBPz) are used as starting agents. The corresponding polymers are named CityU-23 (for polypyridine) and CityU-24 (for polypyrazine). Moreover, it is found that both polymers can form films in situ on different conductive substrates (i.e., silicon, gold, ITO, and nickel), satisfying potential device fabrication. Furthermore, the as-obtained thin films of CityU-23 and CityU-24 exhibit good performance of alkaline hydrogen evolution reaction with the overpotential of 212.8 and 180.7 mV and the Tafel slope of 157.0 and 122.4 mV dec-1, respectively.

A Naphthalenetetracarboxdiimide-Containing Covalent Organic Polymer: Preparation, Single Crystal Structure and Battery Application.

Inspired by dative boron-nitrogen (B←N) bonds proven to be the promising dynamic linkage for the construction of crystalline covalent organic polymers/frameworks (COPs/COFs), we employed 1,4-bis(benzodioxaborole) benzene (BACT) and N,N'-Di(4-pyridyl)-1,4,5,8-naphthalenetetracarboxdiimide (DPNTCDI) as the corresponding building blocks to construct a functional COP (named as CityU-25), which had been employed as an anode in rechargeable lithium ion batteries. CityU-25 displayed an excellent reversible lithium storage capability of 455 mAh/g after 170 cycles at 0.1 A/g, and an impressive one of 673 mAh/g after 720 cycles at 0.5 A/g. These findings suggest that CityU-25 is a standout candidate for advanced battery technologies, highlighting the potential application of this type of materials.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

A High-Fat-Diet-Induced Microbiota Imbalance Correlates with Oxidative Stress and the Inflammatory Response in the Gut of Freshwater Drum (Aplodinotus grunniens).

Lipids are critical nutrients for aquatic animals, and excessive or insufficient lipid intake can lead to physiological disorders, which further affect fish growth and health. In aquatic animals, the gut microbiota has an important regulatory role in lipid metabolism. However, the effects of a high-fat diet on physical health and microbiota diversity in the gut of freshwater drum (Aplodinotus grunniens) are unclear. Therefore, in the present study, a control group (Con, 6%) and a high-fat diet group (HFD, 12%) were established for a 16-week feeding experiment in freshwater drum to explore the physiological changes in the gut and the potential regulatory mechanisms of bacteria. The results indicated that a high-fat diet inhibited antioxidant and immune capacity while increasing inflammation, apoptosis and autophagy in gut cells. Transcriptome analysis revealed significant enrichment in immune-related, apoptosis-related and disease-related pathways. Through 16S rRNA analysis, a total of 31 genus-level differentially abundant bacterial taxa were identified. In addition, a high-fat diet reduced gut microbial diversity and disrupted the ecological balance of the gut microbiota (Ace, Chao, Shannon and Simpson indices). Integrated analysis of the gut microbiota combined with physiological indicators and the transcriptome revealed that gut microbial disorders were associated with intestinal antioxidants, immune and inflammatory responses, cell apoptosis and autophagy. Specifically, genus-level bacterial taxa in Proteobacteria (Plesiomonas, Arenimonas, Erythrobacter and Aquabacteriumb) could serve as potential targets controlling the response to high-fat-diet stimulation.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

Borosilicate-Based Framework: Synthesis, Single-Crystal Structure Study, and Physical Properties.

Herein, we report the synthesis, crystal structure, and optical properties of a metal-free three-dimensional (3D) inorganic covalent framework ((H2en)[Si(B4O9)], named CityU-11, where H2en is the abbreviation for ethanediamine). With the assistance of a tiny amount of F- ions and the selection of SiO2 as Si sources, single crystals of CityU-11 can be successfully prepared under solvothermal conditions. The precise structure information on CityU-11 has been disclosed through both single-crystal X-ray diffraction (SCXRD) and low-dose high-resolution transmission electron microscopy (LD-HRTEM). The SCXRD results showed that CityU-11 crystallized in the noncentrosymmetric space group of Pnn2, while LD-HRTEM suggested that CityU-11 possessed almost the same interplanar distances of 0.6 nm for both (200) and (020) crystal planes, which finely matched with the double peaks of 2θ = 15° in the pattern of its powder X-ray diffraction (PXRD). CityU-11 also displayed an interesting optical property with a moderate birefringence of 0.0258@550 nm.

A Metal-Free Helical Covalent Inorganic Polymer: Preparation, Crystal Structure and Optical Properties.

Helical morphologies are widely observed in nature, however, it is very challenging to prepare artificial helical polymers. Especially, precisely understanding the structure information of artificial metal-free helical covalent inorganic polymers via single-crystal X-ray diffraction (SCXRD) analysis is rarely explored. Here, we successfully prepare a novel metal-free helical covalent inorganic polymer ({[Te(C6 H5 )2 ] [PO3 (OH)]}n , named CityU-10) by introducing angular anions (HOPO3 2- ) into traditional tellurium-oxygen chains. The dynamic reversibility of the reaction is realized through the introduction of organic tellurium precursor and the slow hydrolysis of polyphosphoric acid. High-quality and large-size single crystals of CityU-10 have been successfully characterized via SCXRD, where the same-handed helical inorganic polymer chains form a pseudo-two-dimensional layer via multiple hydrogen-bonding interactions. The left-handed layers and right-handed layers alternatively stack together through weak hydrogen bonds to form a three-dimensional supramolecular structure. The single crystals of CityU-10 are found to display promising optical properties with a large birefringence. Our results would offer new guidelines for designing and preparing new crystalline covalent polymers through tellurium-based chemistry.

Corrigendum: Gut microbes reveal Pseudomonas medicates ingestion preference via protein utilization and cellular homeostasis under feed domestication in freshwater drum, Aplodinotus grunniens.

[This corrects the article DOI: 10.3389/fmicb.2022.861705.].

Conformational Switch of the 250s Loop Enables the Efficient Transglycosylation in GH Family 77.

Amylomaltases (AMs) play important roles in glycogen and maltose metabolism. However, the molecular mechanism is elusive. Here, we investigated the conformational dynamics of the 250s loop and catalytic mechanism of Thermus aquaticus TaAM using path-metadynamics and QM/MM MD simulations. The results demonstrate that the transition of the 250s loop from an open to closed conformation promotes polysaccharide sliding, leading to the ideal positioning of the acid/base. Furthermore, the conformational dynamics can also modulate the selectivity of hydrolysis and transglycosylation. The closed conformation of the 250s loop enables the tight packing of the active site for transglycosylation, reducing the energy penalty and efficiently preventing the penetration of water into the active site. Conversely, the partially closed conformation for hydrolysis results in a loosely packed active site, destabilizing the transition state. These computational findings guide mutation experiments and enable the identification of mutants with an improved disproportionation/hydrolysis ratio. The present mechanism is in line with experimental data, highlighting the critical role of conformational dynamics in regulating the catalytic reactivity of GHs.

Peroxisome Proliferator-Activated Receptor Signaling-Mediated 13-S-Hydroxyoctadecenoic Acid Is Involved in Lipid Metabolic Disorder and Oxidative Stress in the Liver of Freshwater Drum, Aplodinotus grunniens.

The appropriate level of dietary lipids is essential for the nutrient requirements, rapid growth, and health maintenance of aquatic animals, while excessive dietary lipid intake will lead to lipid deposition and affect fish health. However, the symptoms of excessive lipid deposition in the liver of freshwater drums (Aplodinotus grunniens) remain unclear. In this study, a 4-month rearing experiment feeding with high-fat diets and a 6-week starvation stress experiment were conducted to evaluate the physiological alteration and underlying mechanism associated with lipid deposition in the liver of A. grunniens. From the results, high-fat-diet-induced lipid deposition was associated with increased condition factor (CF), viscerosomatic index (VSI), and hepatosomatic index (HSI). Meanwhile, lipid deposition led to physiological and metabolic disorders, inhibited antioxidant capacity, and exacerbated the burden of lipid metabolism. Lipid deposition promoted fatty acid synthesis but suppressed catabolism. Specifically, the transcriptome and metabolome showed significant enrichment of lipid metabolism and antioxidant pathways. In addition, the interaction analysis suggested that peroxisome proliferator-activated receptor (PPAR)-mediated 13-S-hydroxyoctadecenoic acid (13 (s)-HODE) could serve as the key target in regulating lipid metabolism and oxidative stress during lipid deposition in A. grunniens. Inversely, with a lipid intake restriction experiment, PPARs were confirmed to regulate lipid expenditure and physiological homeostasis in A. grunniens. These results uncover the molecular basis of and provide specific molecular targets for fatty liver control and prevention, which are of great importance for the sustainable development of A. grunniens.

Validation and Functional Analysis of Reference and Tissue-Specific Genes in Adipose Tissue of Freshwater Drum, Aplodinotus grunniens, under Starvation and Hypothermia Stress.

Adipose tissue is critical to the growth, development, and physiological health of animals. Reference genes play an essential role in normalizing the expression of mRNAs. Tissue-specific genes are preferred for their function and expression in specific tissues or cell types. Identification of these genes contributes to understanding the tissue-gene relationship and the etiology and discovery of new tissue-specific targets. Therefore, reference genes and tissue-specific genes in the adipose tissue of Aplodinotus grunniens were identified to explore their function under exogenous starvation (1 d, 2 w, 6 w) and hypothermic stress (18 °C and 10 °C for 2 d and 8 d) in this study. Results suggest that 60SRP was the most stable reference gene in adipose tissue. Meanwhile, eight genes were validated as tissue-specific candidates from the high-throughput sequencing database, while seven of them (ADM2, ß2GP1, CAMK1G, CIDE3, FAM213A, HSL, KRT222, and NCEH1) were confirmed in adipose tissue. Additionally, these seven tissue-specific genes were active in response to starvation and hypothermic stress in a time- or temperature-dependent manner. These results demonstrate that adipose-specific genes can be identified using stable internal reference genes, thereby identifying specific important functions under starvation and hypothermic stress, which provides tissue-specific targets for adipose regulation in A. grunniens.

PPAR Signaling Maintains Metabolic Homeostasis under Hypothermia in Freshwater Drum (Aplodinotus grunniens).

Aplodinotus grunniens, known as freshwater drum, is a kind of eurythermal freshwater fish that is widely distributed in North America. In 2019, our research group reached a milestone on its artificial breeding and cultivation and have investigated its physiological adaption to the environment, providing a breakthrough and prospects for aquaculture. However, its adaptability and metabolic homeostasis to hypothermia is not fully understood. In this experiment, cold stress was conducted at 18 °C (LT18) and 10 °C (LT10) with 25 °C as control (Con) for 8 days to explore the effects of short-term hypothermia on the physiology and metabolism of freshwater drum. From the results, the level of free essential amino acids in LT18 and LT10 decreased significantly after 2 days cold stress compared with Con. Furthermore, plasma total triglyceride (TG) content and lipase (LPS) activity were decreased at LT10 for 2d. With RNA-seq in the liver, metabolic-related signaling, especially amino acid synthesis and lipid metabolism, was inhibited by hypothermia. Specifically, the PPAR signaling pathway is correlated with the inhibition of lipid and amino acid metabolism induced by hypothermia. These data confirmed that PPAR signaling maintains lipid and amino acid metabolic homeostasis during cold stress. These results give a theoretical foundation for hypothermia resistance in the area of metabolic homeostasis for freshwater drum.

Stable expression of a truncated TLX variant drives differentiation of induced pluripotent stem cells into self-renewing neural stem cells for production of extracellular vesicles.

BACKGROUND: Neural stem cells (NSCs)-derived extracellular vesicles (EVs) possess great potential in treating severe neurological and cerebrovascular diseases, as they carry the modulatory and regenerative ingredients of NSCs. Induced pluripotent stem cells (iPSCs)-derived NSCs culture represents a sustainable source of therapeutic EVs. However, there exist two major challenges in obtaining a scalable culture of NSCs for high-efficiency EVs production: (1) the heterogeneity of iPSC-derived NSCs culture impairs the production of high-quality EVs and (2) the intrinsic propensity of neuronal or astroglial differentiation of NSCs during prolonged culturing reduces the number of NSCs for preparing EVs. A NSCs strain that is amenable to stable self-renewal and proliferation is thus greatly needed for scalable and long-term culture. METHODS: Various constructs of the genes encoding the orphan nuclear receptor NR2E1 (TLX) were stably transfected in iPSCs, which were subsequently cultured in a variety of differentiation media for generation of iNSCsTLX. Transcriptomic and biomarker profile of iNSCsTLX were investigated. In particular, the positivity ratios of Sox2/Nestin and Musashi/Vimentin were used to gauge the homogeneity of the iNSCsTLX culture. The iNSCs expressing a truncated version of TLX (TLX-TP) was expanded for up to 45 passages, after which its neuronal differentiation potential and EV activity were evaluated. RESULTS: Stable expression of TLX-TP could confer the iPSCs with rapid and self-driven differentiation into NSCs through stable passaging up to 225 days. The long-term culture of NSCs maintained the highly homogenous expression of NSC-specific biomarkers and potential of neuronal differentiation. EVs harvested from the TLX-expressing NSCs cultures exhibited anti-inflammatory and neuroprotective activities. CONCLUSIONS: iPSC-derived NSCs stably expressing TLX-TP is a promising cell line for scalable production of EVs, which should be further exploited for therapeutic development in neurological treatment.

Hypothermia-Mediated Apoptosis and Inflammation Contribute to Antioxidant and Immune Adaption in Freshwater Drum, Aplodinotus grunniens.

Hypothermia-exposure-induced oxidative stress dysregulates cell fate and perturbs cellular homeostasis and function, thereby disturbing fish health. To evaluate the impact of hypothermia on the freshwater drum (Aplodinotus grunniens), an 8-day experiment was conducted at 25 °C (control group, Con), 18 °C (LT18), and 10 °C (LT10) for 0 h, 8 h, 1 d, 2 d, and 8 d. Antioxidant and non-specific immune parameters reveal hypothermia induced oxidative stress and immunosuppression. Liver ultrastructure alterations indicate hypothermia induced mitochondrial enlargement, nucleoli aggregation, and lipid droplet accumulation under hypothermia exposure. With the analysis of the transcriptome, differentially expressed genes (DEGs) induced by hypothermia were mainly involved in metabolism, immunity and inflammation, programmed cell death, and disease. Furthermore, the inflammatory response and apoptosis were evoked by hypothermia exposure in different immune organs. Interactively, apoptosis and inflammation in immune organs were correlated with antioxidation and immunity suppression induced by hypothermia exposure. In conclusion, these results suggest hypothermia-induced inflammation and apoptosis, which might be the adaptive mechanism of antioxidation and immunity in the freshwater drum. These findings contribute to helping us better understand how freshwater drum adjust to hypothermia stress.

miR-1/AMPK-Mediated Glucose and Lipid Metabolism under Chronic Hypothermia in the Liver of Freshwater Drum, Aplodinotus grunniens.

Our previous study demonstrated that low temperature could induce hepatic inflammation and suppress the immune and oxidation resistance of freshwater drum. However, the metabolism, especially the glucose and lipid metabolism involved, is poorly studied. To further explore the chronic hypothermia response of freshwater drum, an 8-day hypothermia experiment was conducted at 10 °C to investigate the effect of chronic hypothermia on glucose and lipid metabolism via biochemical and physiological indexes, and metabolic enzyme activities, miRNAs and mRNA-miRNA integrate analysis in the liver. Plasma and hepatic biochemical parameters reveal chronic hypothermia-promoted energy expenditure. Metabolic enzyme levels uncover that glycolysis was enhanced but lipid metabolism was suppressed. Differentially expressed miRNAs induced by hypothermia were mainly involved in glucose and lipid metabolism, programmed cell death, disease, and cancerization. Specifically, KEGG enrichment indicates that AMPK signaling was dysregulated. mRNA-miRNA integrated analysis manifests miR-1 and AMPK, which were actively co-related in the regulatory network. Furthermore, transcriptional expression of key genes demonstrates hypothermia-activated AMPK signaling by miR-1 and subsequently inhibited the downstream glucogenic and glycogenic gene expression and gene expression of fatty acid synthesis. However, glycogenesis was alleviated to the control level while fatty acid synthesis was still suppressed at 8 d. Meanwhile, the gene expressions of glycolysis and fatty acid oxidation were augmented under hypothermia. In conclusion, these results suggest that miR-1/AMPK is an important target for chronic hypothermia control. It provides a theoretical basis for hypothermia resistance on freshwater drum.

Gut Microbes Reveal Pseudomonas Medicates Ingestion Preference via Protein Utilization and Cellular Homeostasis Under Feed Domestication in Freshwater Drum, Aplodinotus grunniens.

With strong demand for aquatic products, as well as a rapid decrease in global fishery resources and capture fisheries, domesticating animals to provide more high-quality proteins is meaningful for humans. Freshwater drum (Aplodinotus grunniens) is widely distributed in the wild habitats of North America. However, the research on A. grunniens and the feed domestication with diets composed of artificial compounds remains unclear. In this study, a 4-month feeding domestication experiment was conducted with A. grunniens larvae to evaluate the underlying mechanism and molecular targets responsible for alternations in the ingestion performance. The results indicated that a significant increase in the final body weight was exhibited by the feed domesticated group (DOM, 114.8 g) when compared to the group that did not ingest the feed (WT, 5.3 g) as the latest version we raised From the result, the final body weight exhibited significant increase between unfavorable with the feed (WT, 5.3 g) and feed domesticated group (DOM, 114.8 g). In addition, the enzyme activity of digestive enzymes like amylase, lipase, and trypsin was increased in DOM. Genes related to appetite and perception, such as NPY4R, PYY, and LEPR, were activated in DOM. 16s rRNA gene sequencing analysis revealed that Pseudomonas sp. increased from 58.74% to 89.77% in DOM, which accounts for the dominant upregulated microbial community at the genus level, followed by Plesiomonas. Analogously, Mycobacterium, Methylocystis, and Romboutsia also accounted for the down-regulated microbes in the diversity. Transcriptome and RT-PCR analysis revealed that feed domestication significantly improved protein digestion and absorption, inhibited apoptosis by AGE-RAGE signaling, and activated extracellular matrix remodeling by relaxin signaling. Integrated analysis of the microbiome and host transcriptome revealed that Pseudomonas-mediated ingestion capacity, protein utilization, and cellular homeostasis might be the underlying mechanism under feed domestication. These results indicate Pseudomonas and its key genes relating to food ingestion and digestion could serve as the molecular targets for feed domestication and sustainable development in A. grunniens.

TGF-ß Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma.

Background: Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-ß (TGF-ß) may be an important target for novel cancer immunotherapies. Materials and methods: We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency. Result: We established a seven TGF-ß pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib. Conclusion: The TGF-ß pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.

miR-30d-5p: A Non-Coding RNA With Potential Diagnostic, Prognostic and Therapeutic Applications.

Cancer is a great challenge facing global public health. Scholars have made plentiful efforts in the research of cancer therapy, but the results are still not satisfactory. In relevant literature, the role of miRNA in cancer has been widely concerned. MicroRNAs (miRNAs) are a non-coding, endogenous, single-stranded RNAs that regulate a variety of biological functions. The abnormal level of miR-30d-5p, a type of miRNAs, has been associated with various human tumor types, including lung cancer, colorectal cancer, esophageal cancer, prostate cancer, liver cancer, cervical cancer, breast cancer and other types of human tumors. This reflects the vital function of miR-30d-5p in tumor prognosis. miR-30d-5p can be identified either as an inhibitor hindering the development of, or a promoter accelerating the occurrence of tumors. In addition, the role of miR-30d-5p in cell proliferation, motility, apoptosis, autophagy, tumorigenesis, and chemoresistance are also noteworthy. The multiple roles of miR-30d-5p in human cancer suggest that it has broad feasibility as a biomarker and therapeutic target. This review describes the connection between miR-30d-5p and the clinical indications of tumors, and summarizes the mechanisms by which miR-30d-5p mediates cancer progression.

A crucial role for the long non-coding RNA CASC11 in the pathogenesis of human cancers.

Long non-coding RNAs (lncRNAs) are non-coding RNAs more than 200 nucleotides in length. Although they do not encode proteins, lncRNAs can regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging data show that lncRNAs are important for tumorigenesis and cancer progression. Cancer susceptibility candidate 11 (CASC11) is a prominent lncRNA that is upregulated in various types of cancers. Moreover, its overexpression correlates with larger tumor size, more advanced cancer stages, cancer metastasis, and poor overall survival for most types of cancer. Functionally, the knockdown of CASC11 can inhibit cell proliferation, invasion, and migration, while enhancing apoptosis through its regulation of gene expression and signaling pathways and its interactions with functional proteins. Here, we discuss the identification, expression, and function of CASC11. Additionally, we discuss the potential roles of CASC11 as a diagnostic biomarker, prognostic biomarker, and therapeutic target in various cancers.