Free fatty acid (FFA) and acylcarnitine (AcCar) are key elements of energy metabolism. Dysregulated levels of FFA and AcCar are associated with genetic defects and other metabolic disorders. Due to ...differences in the physicochemical properties of these two classes of compounds, it is challenging to quantify FFA and AcCar in human plasma using a single method. In this work, we developed a chemical isotope labeling (CIL)–based liquid chromatography–multiple reaction monitoring (LC-MRM) method to simultaneously quantify FFA and AcCar. Dansylhydrazine (DnsHz) was used to label the carboxylic acid moiety on FFA and AcCar. This resulted in the formation of a permanently charged ammonium ion for facile ionization in positive ionization mode and higher hydrophobicity for enhanced retention of short-chain analogs on reversed-phase LC columns and enabled absolute quantification by using heavy labeled DnsHz analogs as internal standards. Labeling conditions including the concentration and freshness of cross-linker, reaction time, and temperature were optimized. This method can successfully quantify all short-, medium- and long-chain FFAs and AcCars with greatly enhanced sensitivity. Using this method, 25 FFAs and 13 AcCars can be absolutely quantified and validated in human plasma samples within 12 min. Simultaneous quantification of FFA and AcCar enabled by this CIL-based LC-MRM method facilitates the investigation of fatty acid metabolism and has potential in clinical applications.
Mesoporous materials have attracted considerable attention because of their distinctive properties, including high surface areas, large pore sizes, tunable pore structures, controllable chemical ...compositions, and abundant forms of composite materials. During the last decade, there has been increasing research interest in constructing advanced mesoporous nanomaterials possessing short and open channels with efficient mass diffusion capability and rich accessible active sites for electrochemical energy conversion and storage. Here, the synthesis, structures, and energy‐related applications of mesoporous nanomaterials are the main focus. After a brief summary of synthetic methods of mesoporous nanostructures, the delicate design and construction of mesoporous nanomaterials are described in detail through precise tailoring of the particle sizes, pore sizes, and nanostructures. Afterward, their applications as electrode materials for lithium‐ion batteries, supercapacitors, water‐splitting electrolyzers, and fuel cells are discussed. Finally, the possible development directions and challenges of mesoporous nanomaterials for electrochemical energy conversion and storage are proposed.
Mesoporous nanomaterials have attracted significant attention in various important fields, especially as electrode materials or catalysts for energy storage and conversion devices. A comprehensive overview of the synthetic strategies and recent developments of mesoporous nanostructures, their electrochemical properties in energy storage and conversion systems, and future directions for design and synthesis of advanced mesoporous nanostructures are provided.
Quantum key distribution (QKD) provides a promising solution for sharing information-theoretic secure keys between remote peers with physics-based protocols. According to the law of quantum physics, ...the photons carrying signals cannot be amplified or relayed via classical optical techniques to maintain quantum security. As a result, the transmission loss of the channel limits its achievable distance, and this has been a huge barrier towards building large-scale quantum-secure networks. Here we present an experimental QKD system that could tolerate a channel loss beyond 140 dB and obtain a secure distance of 833.8 km, setting a new record for fibre-based QKD. Furthermore, the optimized four-phase twin-field protocol and high-quality set-up make its secure key rate more than two orders of magnitude greater than previous records over similar distances. Our results mark a breakthrough towards building reliable and efficient terrestrial quantum-secure networks over a scale of 1,000 km.Twin-field (TF) quantum key distribution (QKD) over a secure distance of 833.8 km is demonstrated even in the finite-size regime. To this end, an optimized four-phase TF-QKD protocol and a high-speed low-noise TF-QKD system are developed.
Single-atom catalysts (SACs) with their unique electronic and geometric structures usually exhibit extraordinary catalytic performance for many important chemical reactions. Herein, a modular ...strategy is used to decorate isolated cobalt sites into a multichannel carbon matrix (Co@MCM) with Co content of about 1.4 wt% for efficient electrochemical reduction of oxygen. As confirmed by X-ray absorption fine structure investigation, the pre-designed CoN 4 configuration and geometric structure are well maintained in the newly developed Co@MCM. The decorated CoN 4 units together with the multichannel carbon substrate with high conductivity and porosity endow the catalyst with excellent activity for the oxygen reduction reaction (ORR). Our findings not only present some fundamental insights for the accurate modulation of nanostructured catalysts at the atomic scale, but also reveal the structural origin of the enhanced catalytic activity.
Metastasis causes the vast majority of colorectal carcinoma (CRC)-related deaths. However, little is known about the specific traits and underlying mechanisms of metastasis-initiating cells in ...primary CRC. And whether or not circular RNAs (circRNAs) take part in this particular event remain not adequately stated yet.
A screening method based on Transwell assay was first applied to build CRC subgroups with different metastatic potential. High throughput RNA sequencing was used to find out novel metastatic drivers in CRC metastasis-initiating step. A series of in vitro and in vivo assays were further applied to elucidate the functions and underlying molecular mechanisms of circRNAs in CRC metastasis.
A circRNA consisting of exon 8-11 of LONP2, termed as circLONP2, was upregulated in metastasis-initiating CRC subgroups. Aberrant higher expression of circLONP2 was observed in primary CRC tissues with established metastasis, and along the invasive margin in metastatic site. High expression of circLONP2 predicted unfavorable overall survival. Functional studies revealed that circLONP2 could enhance the invasiveness of CRC cells in vitro, and targeting circLONP2 through anti-sense oligonucleotide (ASO) dramatically reduced the penetrance of metastasis to foreign organs in vivo. Mechanically, circLONP2 directly interacted with and promoted the processing of primary microRNA-17 (pri-miR-17), through recruiting DiGeorge syndrome critical region gene 8 (DGCR8) and Drosha complex in DDX1-dependent manner. Meanwhile, upregulated mature miR-17-5p could be assembled into exosomes and internalized by neighboring cells to enhance their aggressiveness.
Our data indicate that circLONP2 acts as key metastasis-initiating molecule during CRC progression through modulating the intracellular maturation and intercellular transfer of miR-17, resulting in dissemination of metastasis-initiating ability in primary site and acceleration of metastasis formation in foreign organs. circLONP2 could serve as an effective prognostic predictor and/or novel anti-metastasis therapeutic target in CRC treatment.
Oxylipins, a subclass of lipid mediators, are metabolites of various polyunsaturated fatty acids with crucial functions in regulation of systemic inflammation. Elucidation of their roles in ...pathological conditions requires accurate quantification of their levels in biological samples. We refined an ultra-performance liquid chromatography-multiple reaction monitoring-mass spectrometry (UPLC-MRM-MS)-based workflow for comprehensive and specific quantification of 131 endogenous oxylipins in human plasma, in which we optimized LC mobile phase additives, column, and gradient conditions. We employed heatmap-assisted strategy to identify unique transitions to improve the assay selectivity and optimized solid phase extraction procedures to achieve better analyte recovery. The method was validated according to FDA guidelines. Overall, 94.4% and 95.7% of analytes at tested concentrations were within acceptable accuracy (80–120%) and precision (CV < 15%), respectively. Good linearity for most analytes was obtained with
R
2
> 0.99. The method was also validated using a standard reference material—SRM 1950 frozen human plasma to demonstrate inter-lab compatibility.
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Growing evidences suggest that cancer stem cells exhibit many molecular characteristics and phenotypes similar to their ancestral progenitor cells. In the present study, human embryonic stem cells ...are induced to differentiate into hepatocytes along hepatic lineages to mimic liver development in vitro. A liver progenitor specific gene, RALY RNA binding protein like (RALYL), is identified. RALYL expression is associated with poor prognosis, poor differentiation, and metastasis in clinical HCC patients. Functional studies reveal that RALYL could promote HCC tumorigenicity, self-renewal, chemoresistance, and metastasis. Moreover, molecular mechanism studies show that RALYL could upregulate TGF-β2 mRNA stability by decreasing N6-methyladenosine (m
A) modification. TGF-β signaling and the subsequent PI3K/AKT and STAT3 pathways, upregulated by RALYL, contribute to the enhancement of HCC stemness. Collectively, RALYL is a liver progenitor specific gene and regulates HCC stemness by sustaining TGF-β2 mRNA stability. These findings may inspire precise therapeutic strategies for HCC.
The tumor microenvironment (TME) of nasopharyngeal carcinoma (NPC) harbors a heterogeneous and dynamic stromal population. A comprehensive understanding of this tumor-specific ecosystem is necessary ...to enhance cancer diagnosis, therapeutics, and prognosis. However, recent advances based on bulk RNA sequencing remain insufficient to construct an in-depth landscape of infiltrating stromal cells in NPC. Here we apply single-cell RNA sequencing to 66,627 cells from 14 patients, integrated with clonotype identification on T and B cells. We identify and characterize five major stromal clusters and 36 distinct subpopulations based on genetic profiling. By comparing with the infiltrating cells in the non-malignant microenvironment, we report highly representative features in the TME, including phenotypic abundance, genetic alternations, immune dynamics, clonal expansion, developmental trajectory, and molecular interactions that profoundly influence patient prognosis and therapeutic outcome. The key findings are further independently validated in two single-cell RNA sequencing cohorts and two bulk RNA-sequencing cohorts. In the present study, we reveal the correlation between NPC-specific characteristics and progression-free survival. Together, these data facilitate the understanding of the stromal landscape and immune dynamics in NPC patients and provides deeper insights into the development of prognostic biomarkers and therapeutic targets in the TME.
As the country with the largest aging population, China faces an enormous challenge with its elderly support and care. One of the proposed solutions is the development of volunteerism for elderly ...care. The Senior Care Volunteers Training Program (SCVTP) was initiated by the Red Cross Society of China with the purpose of training volunteers to care for community seniors. As one of the four pilot provinces, Jiangsu Province launched the program since 2017. The present study was conducted to investigate the dropout rate of trained volunteer group leaders, the characteristics of the retained trained volunteer group leaders and the activities that their groups conducted. Additionally, the exploration of the factors influencing the SCVTP's performance was listed as another aim. A cross-sectional study was designed. The study used purposive sampling to select participants who meet the criteria from all the trained volunteer group leaders (n = 623). Demographic questionnaire, volunteer role identity (VRI) scale, attitude toward helping others (AHO) scale, team climate and atmosphere (TCA) scale, and volunteer program performance evaluation (VPPE) questionnaire were used to collect the data online. Descriptive statistics were used to determine the dropout rate and general characteristics of the retained volunteers and the activities. A multiple linear regression equation was developed to study the factors that influence program performance. In total, 307 questionnaires were valid in the study. About 67.9%, 53.7%, and 30.0% of the trained volunteer group leaders dropped out of the program in the year of 2017, 2018, and 2019, respectively. The retained trained volunteer group leaders were more likely to be females (84.7%), those in excellent health (75.2%) and with a bachelor's degree or above (87.6%). Less attention has been paid to frailty care (n = 76) than other volunteer caring activities (e.g., safe care: n = 277, diet care: n = 250, drug management care: n = 226). VRI (beta = 0.118, p = 0.017), AHO (beta = 0.134, p = 0.021), TCA (beta = 0.459, p<0.001), and financial sustainability (beta = 0.179, p<0.001) affected the SCVTP's performance significantly (adjusted R.sup.2 = 0.356). High rate of trained volunteer group leaders' dropout should be brought to the policymaker's attention. The characteristics of the retained trained volunteer group leaders provide a useful reference for the recruitment of trainees in the future. Frailty care may need more training by the volunteer service provider. In order to enhance program performance, a better team climate and atmosphere, financial sustainability, and volunteers with appropriate attitude and role identity are also necessary for the volunteer program.
There is increasing evidence that hexokinase is involved in cell proliferation and migration. However, the function of the hexokinase domain containing protein‐1 (HKDC1) in gastric cancer (GC) ...remains unclear. Immunohistochemistry analysis and big data mining were used to evaluate the correlation between HKDC1 expression and clinical features in GC. In addition, the biological function and molecular mechanism of HKDC1 in GC were studied by in vitro and in vivo assays. Our study indicated that HKDC1 expression was upregulated in GC tissues compared with adjacent nontumor tissues. High expression of HKDC1 was associated with worse prognosis. Functional experiments demonstrated that HKDC1 upregulation promoted glycolysis, cell proliferation, and tumorigenesis. In addition, HKDC1 could enhance GC invasion and metastasis by inducing epithelial–mesenchymal transition (EMT). Abrogation of HKDC1 could effectively attenuate its oncogenic and metastatic function. Moreover, HKDC1 promoted GC proliferation and migration in vivo. HKDC1 overexpression conferred chemoresistance to cisplatin, oxaliplatin, and 5‐fluorouracil (5‐Fu) onto GC cells. Furthermore, nuclear factor kappa‐B (NF‐κB) inhibitor PS‐341 could attenuate tumorigenesis, metastasis, and drug resistance ability induced by HKDC1 overexpression in GC cells. Our results highlight a critical role of HKDC1 in promoting glycolysis, tumorigenesis, and EMT of GC cells via activating the NF‐κB pathway. In addition, HKDC1‐mediated drug resistance was associated with DNA damage repair, which further activated NF‐κB signaling. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.
HKDC1 upregulation predicts resistance to cisplatin, oxaliplatin and 5‐FU in patients with GC. HKDC1 upregulation may be used as a potential indicator for choosing an effective chemotherapy regimen for GC patients undergoing chemotherapy.
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