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Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.

Molybdenum diselenide (MoSe2) is a promising anode for alkali-ion storage due to its intrinsic advantages. However, MoSe2 still encounters the issues of structural instability and poor rate performance caused by drastic volume change and sluggish reaction kinetics. Reasonable design of electrode structure is crucial for achieving superior electrochemical performance. Herein, a novel hierarchical structure coupled with 1D/1D subunits is elaborately designed and constructed, in which the MoSe2/CoSe2 heterostructure is the “trunk” and the N-doped carbon nanotubes are the “branches” (MoSe2/CoSe2/NCNTs). Benefiting from the properties endowed by unique configurations, MoSe2/CoSe2/NCNTs electrodes manifest faster reaction kinetics and better structure durability. Evaluated as an anode for LIBs and SIBs, MoSe2/CoSe2/NCNTs deliver high reversible capacity, superior rate capability (452 at 10 A g−1 in LIBs and 296 at 10 A g−1 in SIBs), and prominent cycle life (553 after 2000 cycles at 5 A g−1 in LIBs and 310 after 2000 cycles at 5 A g−1 in SIBs). Such design conception can also provide guidance for the development of other high-performance electrodes.

Stem cell therapy is a promising treatment for knee osteoarthritis, but few bibliometric studies have been performed on the subject. Bibliometric analysis is helpful for identifying the most influential studies in a specific field and can evaluate the global research trends in stem cell therapy for knee osteoarthritis. The Web of Science Core Collection was searched for publications from 2001 to 2021. Publication performance was analyzed using several bibliometric parameters, including VOSviewer, to identify the research landscape of trends in topics, and CiteSpace was investigated to identify the keywords that have the strongest citation bursts. From 2001 to 2021, in total, 1,345 publications explored the research on stem cells in knee osteoarthritis. The United States contributed the largest number of publications and at the top list of international collaborations. Tokyo Medical and Dental University ranked first among institutions in the overall number of articles and citations. The journal of Osteoarthritis and Cartilage had the largest number of publications. Sekiya Ichiro was the most cited author, with 32 articles. The keywords with the most frequent occurrence were “osteoarthritis,” “mesenchymal stem cells,” and “cartilage,” in descending order of frequency. “fibroblast growth factor” and “extracellular vesicle” were the first and last searched theme terms, respectively. The number of publications on stem cells for knee osteoarthritis stays growing. Cartilage repair and paracrine function are current research hotspots for the stem cell therapy mechanism. Stem cell therapy has gradually advanced from basic research to the clinical application stage.

Abstract Background Ex vivo and in vivo detection and imaging of adenosine triphosphate (ATP) is critically important for the diagnosis and treatment of diseases, which still remains challenges up to present. Results We herein demonstrate that ATP could be fluorescently detected and imaged ex vivo and in vivo. In particular, we fabricate a kind of fluorescent ATP probes, which are made of titanium carbide (TC) nanosheets modified with the ROX-tagged ATP-aptamer (TC/Apt). In the constructed TC/Apt, TC shows superior quenching efficiency against ROX (e.g., ~ 97%). While in the presence of ATP, ROX-tagged aptamer is released from TC surface, leading to the recovery of fluorescence of ROX under the 545-nm excitation. Consequently, a wide dynamic range from 1 μM to 1.5 mM ATP and a high sensitivity with a limit of detection (LOD) down to 0.2 μM ATP can be readily achieved by the prepared TC/Apt. We further demonstrate that the as-prepared TC/Apt probe is feasible for accurate discrimination of ATP in different samples including living cells, body fluids (e.g., mouse serum, mouse urine and human serum) and mouse tumor models. Conclusions Fluorescence detection and imaging of ATP could be readily achieved in living cells, body fluids (e.g., urine and serum), as well as mouse tumor model through a new kind of fluorescent ATP nanoprobes, offering new powerful tools for the treatment of diseases related to abnormal fluctuation of ATP concentration.

ABSTRACT Biomphalaria glabrata transmits schistosomiasis mansoni which poses considerable risks to hundreds of thousands of people worldwide, and is widely used as a model organism for studies on the snail-schistosome relationship. Gut microbiota plays important roles in multiple aspects of host including development, metabolism, immunity, and even behavior; however, detailed information on the complete diversity and functional profiles of B. glabrata gut microbiota is still limited. This study is the first to reveal the gut microbiome of B. glabrata based on metagenome-assembled genome (MAG). A total of 28 gut samples spanning diet and age were sequenced and 84 individual microbial genomes with ≥ 70% completeness and ≤ 5% contamination were constructed. Bacteroidota and Proteobacteria were the dominant bacteria in the freshwater snail, unlike terrestrial organisms harboring many species of Firmicutes and Bacteroidota. The microbial consortia in B. glabrata helped in the digestion of complex polysaccharide such as starch, hemicellulose, and chitin for energy supply, and protected the snail from food poisoning and nitrate toxicity. Both microbial community and metabolism of B. glabrata were significantly altered by diet. The polysaccharide-degrading bacterium Chryseobacterium was enriched in the gut of snails fed with high-digestibility protein and high polysaccharide diet (HPHP). Notably, B. glabrata as a mobile repository can escalate biosafety issues regarding transmission of various pathogens such as Acinetobacter nosocomialis and Vibrio parahaemolyticus as well as multiple antibiotic resistance genes in the environment and to other organisms. IMPORTANCE The spread of aquatic gastropod Biomphalaria glabrata, an intermediate host of Schistosoma mansoni, exacerbates the burden of schistosomiasis disease worldwide. This study provides insights into the importance of microbiome for basic biological activities of freshwater snails, and offers a valuable microbial genome resource to fill the gap in the analysis of the snail-microbiota-parasite relationship. The results of this study clarified the reasons for the high adaptability of B. glabrata to diverse environments, and further illustrated the role of B. glabrata in accumulation of antibiotic resistance in the environment and spread of various pathogens. These findings have important implications for further exploration of the control of snail dissemination and schistosomiasis from a microbial perspective.

BackgroundErlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, demonstrated therapeutic efficacy against pancreatic cancer. However, acquired resistance to erlotinib in pancreatic cancer is widely observed, and the exact mechanisms have not been fully explored until now. We examined the role of circular RNA circ_0013587 in the acquired resistance to erlotinib in pancreatic cancer cells and explored the underlying mechanisms.MethodsWe selected erlotinib-resistant pancreatic cancer cells from the AsPC-1 cell line. The expression of circ_0013587 was examined by qRT-PCR assays. The effects of circ_0013587 on pancreatic cancer cell proliferation, invasion, and erlotinib resistance were assessed by cell functional assays. Bioinformatic analysis and dual-luciferase reporter assays identified circ_0013587 and E-cadherin as direct targets of miR-1227. Mouse xenograft models were employed to investigate the function of circ_0013587 in erlotinib resistance of tumors in vivo.ResultsCirc_0013587 expression was significantly reduced in erlotinib-resistant AsPC-1 cells. We found that increasing circ_0013587 levels in erlotinib-resistant AsPC-1 cells re-sensitized them, whereas reducing circ_0013587 levels in erlotinib-sensitive AsPC-1 cells made them resistant. Mechanically, circ_0013587 released E-cadherin from the suppression of miR-1227, leading to E-cadherin up-regulation. Rescue assays highlighted that circ_0013587 reversed erlotinib resistance in pancreatic cancer cells by increasing E-cadherin levels through reducing the expression of miR-1227. Furthermore, circ_0013587 overexpression sensitized erlotinib-resistant AsPC-1 cells to erlotinib in xenograft models.ConclusionsOur results demonstrated that down-regulation of circ_0013587 contributes to acquired resistance to erlotinib in pancreatic cancer cells through mediating the miR-1227/E-cadherin pathway and that circ_0013587 is a potential target molecular to overcome erlotinib resistance.

Puerarin, the most important flavonoid in Puerariae Lobatae Radix (PLR), has high biological activity but poor oral absorption. This study investigated how to enhance the absorption and pharmacokinetics of puerarin through modulating the intestinal barrier. Analyses of intestinal absorption, pharmacokinetics demonstrated enhanced puerarin absorption with daidzin, daidzein and ligustrazine (the main active ingredient in vinegar and Chuanxiong Rhizoma (CXR)). In particular, PLR combined with CXR enhanced the absorption and pharmacokinetics of puerarin through elevating puerarin solubility, regulating P-glycoprotein efflux and reducing claudin-5 expression. The combination of PLR and CXR reduced the diversity of gut microbiota and the ratio of Firmicutes to Bacteroidetes. In conclusion, combining PLR with CXR enhanced the absorption and pharmacokinetics of puerarin by modulating the intestinal barrier and influenced gut microbiota. The gut microbiota is likely to be a potential target for the combination of PLR and CXR.

Post-pulse-compression is demanded to produce energetic few-cycle pulses. We propose pre-chirp-managed adiabatic soliton compression (ASC) in gas-filled pressure-gradient hollow-core fibers to suppress the detrimental pedestals and therefore significantly improve the compressed pulse quality. We show that two-stage ASC can compress 125 μJ, 130 fs pulses at 2 μm to a nearly two-cycle pulse 15 fs in duration. Our analytical analysis suggests that ASC is in favor of compressing pulses centered at a longer wavelength. As an example, a 280 μJ, 220 fs Gaussian pulse at 4 μm is compressed to 60 fs with minimal pedestals. We expect that the resulting high-quality, energetic few-cycle pulses will find important applications in high-field science.

Introduction: Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or L-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors. Conclusions: Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors. [ABSTRACT FROM AUTHOR]

Medical electrical impedance tomography (EIT) reconstruction algorithms are approximately forty years old and are now being used to treat patients. At the same time, many advanced concepts are still active research areas, and literature regarding EIT algorithms has been presented in different professional journals and scientific conferences. Bibliometrics analysis method is used to assess the 30 years of scientific output and activity regarding EIT algorithm research from a global perspective, covering global publications, cooperation between countries, and clustering of keywords. 2467 research articles, reviews, letters, and proceeding papers published from 1987 to 2021 in English on EIT reconstruction algorithm were analyzed. Literature statistics show that the worldwide growth trend is rising, and global geographic distribution of publications in this field indicates that USA, South Korea, and China ranked as the top three prolific contributors in terms of EIT algorithm. "inverse problem" "regularization""electrode models" were research focus. Overall, EIT algorithms bibliometric research provides the current hotspots and future directions of algorithm research. [ABSTRACT FROM AUTHOR]