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1.
Front Behav Neurosci ; 18: 1341901, 2024.
Article En | MEDLINE | ID: mdl-38698886

Prion diseases, such as scrapie, entail the accumulation of disease-specific prion protein (PrPSc) within the brain. Toll-like receptors (TLRs) are crucial components of the pattern recognition system. They recognize pathogen-associated molecular patterns (PAMPs) and play a central role in orchestrating host innate immune responses. The expression levels of Toll-like receptors (TLRs) in the central nervous system (CNS) were not well-defined. To establish a model of prion diseases in BALB/C mice, the 22L strain was employed. The features of the 22L strain were analyzed, and the cerebellum exhibited severe pathological changes. TLR1-13 levels in the cerebellum were measured using quantitative polymerase chain reaction (qPCR) at time points of 60, 90, 120, and the final end point (145 days post-infection). During the pathogenesis, the expression levels of Toll-like receptors (TLRs) 1, 2, 7, 8, and 9 increased in a time-dependent manner. This trend mirrored the expression patterns of PrPSc (the pathological isoform of the prion protein) and glial fibrillary acidic protein. Notably, at the end point, TLR1-13 levels were significantly elevated. Protein level of TLR7 and TLR9 showed increasing at the end point of the 22L-infected mice. A deeper understanding of the increased Toll-like receptors (TLRs) in prion diseases could shed light on their role in initiating immune responses at various stages during pathogenesis. This insight is particularly relevant when considering TLRs as potential therapeutic targets for prion diseases.

2.
Anal Bioanal Chem ; 416(13): 3195-3203, 2024 May.
Article En | MEDLINE | ID: mdl-38613682

We propose a sensitive H1N1 virus fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies. Products are generated via the hybridization of single-stranded DNA (ssDNA) probes containing T7 promoter and crRNA templates to a target RNA sequence using SplintR ligase. This generates large crRNA quantities in the presence of T7 RNA polymerase. At such crRNA quantities, ternary Cas13a, crRNA, and activator complexes are successfully constructed and activate Cas13a to enhance fluorescence signal outputs. The biosensor sensitively and specifically monitored H1N1 viral RNA levels down to 3.23 pM and showed good linearity when H1N1 RNA concentrations were 100 pM-1 µM. Biosensor specificity was also excellent. Importantly, our biosensor may be used to detect other viral RNAs by altering the sequences of the two probe junctions, with potential applications for the clinical diagnosis of viruses and other biomedical studies.


Biosensing Techniques , CRISPR-Cas Systems , Influenza A Virus, H1N1 Subtype , RNA, Viral , Biosensing Techniques/methods , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/isolation & purification , RNA, Viral/analysis , RNA, Viral/genetics , Nucleic Acid Amplification Techniques/methods , Humans , Limit of Detection , Fluorescence , Transcription, Genetic
3.
Bioorg Med Chem Lett ; 106: 129774, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38688438

Herein, we constructed a fluorescence biosensor for the ultra-sensitive analysis of microRNAs (miRNAs) by combining DNA hairpins transition triggered strand displacement amplification (DHT-SDA) with primer exchange reaction (PER). Target miRNA initiated DHT-SDA to facilitate the generation of multiple single-stranded DNA (ssDNA) as PER primer, which was extended into a long ssDNA. The biosensor is successfully utilized in detecting miRNAs with high sensitivity (limit of detection for miRNA-21 was 58 fM) and a good linear relationship between 100 nM and 100 fM. By simply changing the DNA hairpin sequence, the constructed biosensor can be extended to analyze another miRNAs. Moreover, the biosensor has the feasibility of detecting miRNAs in real samples with satisfactory accuracy and reliability. Therefore, the fluorescent biosensor has great application potential in clinical diagnosis.


Biosensing Techniques , MicroRNAs , Nucleic Acid Amplification Techniques , MicroRNAs/metabolism , MicroRNAs/analysis , Humans , DNA/chemistry , DNA, Single-Stranded/chemistry , DNA, Single-Stranded/metabolism , Fluorescence , Inverted Repeat Sequences , Spectrometry, Fluorescence , Limit of Detection , DNA Primers/chemistry
4.
BMC Cancer ; 24(1): 523, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664760

BACKGROUND: Although numerous studies have reported the prognostic value of the lung immune prognostic index (LIPI) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), the prognostic value of the LIPI in a pancancer setting remains unclear. METHODS: A comprehensive search was conducted until July 2023 across the PubMed, Embase, Web of Science, and Cochrane Library databases to identify relevant studies evaluating the prognostic value of the LIPI in cancer patients treated with ICIs. The outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). We described and compared the pooled outcomes by stratifying the patients based on different groupings of LIPI (good vs. intermediate [0 vs. 1], good vs. poor [0 vs. 2], and good vs. intermediate / poor [0 vs. 1 + 2]). RESULTS: A total of 9959 patients in 35 studies were included. A higher score of LIPI was associated with impaired OS. The pooled HRs were 1.69 (95% CI: 1.55-1.85, p < 0.001; 0 vs. 1), 3.03 (95% CI: 2.53-3.63, p < 0.001; 0 vs. 2), and 2.38 (95% CI: 1.97-2.88, p < 0.001; 0 vs. 1 + 2). A higher LIPI score was associated with shorter PFS. The pooled HRs were 1.41 (95% CI: 1.31-1.52, p < 0.001; 0 vs. 1), 2.23 (95% CI: 1.87-2.66, p < 0.001; 0 vs. 2), and 1.65 (95% CI: 1.46-1.86, p < 0.001; 0 vs. 1 + 2). Similarly, a higher LIPI score was associated with a lower ORR. The pooled ORs were 0.63 (95% CI: 0.54-0.75, p < 0.001; 0 vs. 1) and 0.38 (95% CI: 0.29-0.50, p < 0.001; 0 vs. 2). A higher LIPI score was associated with a lower DCR. The pooled ORs were 0.47 (95% CI: 0.35-0.61, p < 0.001; 0 vs. 1) and 0.19 (95% CI: 0.12-0.30, p < 0.001; 0 vs. 2). CONCLUSION: In patients with NSCLC or other solid tumours, the lung immune prognostic index could robustly stratify the clinical outcomes into three groups among the patients who receive ICIs. LIPI is a low-cost, simple, accessible, and accurate prognostic tool in a pancancer setting and it may contribute to the evaluation of risk stratification in patients treated with ICIs.


Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Progression-Free Survival
5.
Nat Commun ; 15(1): 1056, 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38316839

As the core component of solid-state batteries, neither current inorganic solid-state electrolytes nor solid polymer electrolytes can simultaneously possess satisfactory ionic conductivity, electrode compatibility and processability. By incorporating efficient Li+ diffusion channels found in inorganic solid-state electrolytes and polar functional groups present in solid polymer electrolytes, it is conceivable to design inorganic-organic hybrid solid-state electrolytes to achieve true fusion and synergy in performance. Herein, we demonstrate that traditional metal coordination compounds can serve as exceptional Li+ ion conductors at room temperature through rational structural design. Specifically, we synthesize copper maleate hydrate nanoflakes via bottom-up self-assembly featuring highly-ordered 1D channels that are interconnected by Cu2+/Cu+ nodes and maleic acid ligands, alongside rich COO- groups and structural water within the channels. Benefiting from the combination of ion-hopping and coupling-dissociation mechanisms, Li+ ions can preferably transport through these channels rapidly. Thus, the Li+-implanted copper maleate hydrate solid-state electrolytes shows remarkable ionic conductivity (1.17 × 10-4 S cm-1 at room temperature), high Li+ transference number (0.77), and a 4.7 V-wide operating window. More impressively, Li+-implanted copper maleate hydrate solid-state electrolytes are demonstrated to have exceptional compatibility with both cathode and Li anode, enabling long-term stability of more than 800 cycles. This work brings new insight on exploring superior room-temperature ionic conductors based on metal coordination compounds.

6.
Nat Commun ; 15(1): 983, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-38302469

The nanoreactor holds great promise as it emulates the natural processes of living organisms to facilitate chemical reactions, offering immense potential in catalytic energy conversion owing to its unique structural functionality. Here, we propose the utilization of precisely engineered carbon spheres as building blocks, integrating micromechanics and controllable synthesis to explore their catalytic functionalities in two-electron oxygen reduction reactions. After conducting rigorous experiments and simulations, we present compelling evidence for the enhanced mass transfer and microenvironment modulation effects offered by these mesoporous hollow carbon spheres, particularly when possessing a suitably sized hollow architecture. Impressively, the pivotal achievement lies in the successful screening of a potent, selective, and durable two-electron oxygen reduction reaction catalyst for the direct synthesis of medical-grade hydrogen peroxide disinfectant. Serving as an exemplary demonstration of nanoreactor engineering in catalyst screening, this work highlights the immense potential of various well-designed carbon-based nanoreactors in extensive applications.

7.
Sci Rep ; 14(1): 1030, 2024 01 10.
Article En | MEDLINE | ID: mdl-38200187

Recently, the efficacy of two low-invasive treatments, ablation, and radiotherapy, has been fully compared for the patients with the early-stage hepatocellular carcinoma (HCC). However, the comparison between radiotherapy plus ablation and ablation alone has been less frequently reported. Data from the Surveillance, Epidemiology, and End Results (SEER) database were searched for early-stage HCC patients treated with ablation plus radiotherapy or ablation alone. The outcome measures were overall survival (OS) and cancer-specific survival (CSS). The propensity score matching (PSM) was used to reduce selection bias. We included 240 and 6619 patients in the radiotherapy plus ablation group and ablation group before the PSM. After PSM, 240 pairs of patients were included. The median OS (mOS) and median CSS (mCSS) of patients receiving ablation alone were longer than that of receiving radiotherapy plus ablation (mOS: 47 vs. 34 months, P = 0.019; mCSS: 77 vs. 40 months, P = 0.018, after PSM) before and after PSM. The multivariate analysis indicated that radiotherapy plus ablation independent risk factor for OS and CSS before PSM, but the significance disappeared after PSM. The detailed subgroup analyses indicated ablation alone brought more benefit in very early-stage HCC and older patients. In addition, we found different types of radiotherapy might lead to different outcomes when combined with ablation. In conclusion, ablation alone is noninferior to radiotherapy plus ablation in patients with early-stage HCC. The additional radiation prior to ablation may bring survival benefits in the patients with higher tumor stage. However, due to the risk of selection bias in that study, the results should be interpreted cautiously.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/radiotherapy , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/radiotherapy , Liver Neoplasms/surgery , Research , Databases, Factual , Multivariate Analysis
8.
Nano Lett ; 24(5): 1650-1659, 2024 Feb 07.
Article En | MEDLINE | ID: mdl-38265360

Precision nanoengineering of porous two-dimensional structures has emerged as a promising avenue for finely tuning catalytic reactions. However, understanding the pore-structure-dependent catalytic performance remains challenging, given the lack of comprehensive guidelines, appropriate material models, and precise synthesis strategies. Here, we propose the optimization of two-dimensional carbon materials through the utilization of mesopores with 5-10 nm diameter to facilitate fluid acceleration, guided by finite element simulations. As proof of concept, the optimized mesoporous carbon nanosheet sample exhibited exceptional electrocatalytic performance, demonstrating high selectivity (>95%) and a notable diffusion-limiting disk current density of -3.1 mA cm-2 for H2O2 production. Impressively, the electrolysis process in the flow cell achieved a production rate of 14.39 mol gcatalyst-1 h-1 to yield a medical-grade disinfectant-worthy H2O2 solution. Our pore engineering research focuses on modulating oxygen reduction reaction activity and selectivity by affecting local fluid transport behavior, providing insights into the mesoscale catalytic mechanism.

9.
Front Oncol ; 13: 1285209, 2023.
Article En | MEDLINE | ID: mdl-38090478

Cancer metabolism has emerged as a pivotal area of research recently. The ability to visualize and comprehend the metabolic processes of cancer holds immense clinical value, particularly in the diagnosis of malignant tumors and the assessment of treatment responses. Deuterium Metabolic Imaging (DMI), as a robust, simple, and versatile MR spectroscopic imaging tool, demonstrates promise in tumor diagnosis and treatment efficacy assessment. This review explored the latest developments and applications of DMI in oncology across various tumor metabolic axes, with a specific emphasis on its potential for clinical translation. DMI offers invaluable insights into tumor biology, treatment responses, and prognostic outcomes. Notably, DMI can identify early responses to immunotherapy, a prominent area of current research interest. In conclusion, DMI harbors the potential to evolve into a convenient and efficient imaging technique in clinical practice, thereby advancing precision medicine and improving the diagnosis and evaluation of cancer treatments.

10.
Eur J Radiol ; 165: 110911, 2023 Aug.
Article En | MEDLINE | ID: mdl-37300937

PURPOSE: To discriminate between benignities and hepatocellular carcinomas (HCCs) in patients at high risk of HCC using a novel enhancement flux analysis for gadoxetic-acid enhanced MRI. METHOD: This study retrospectively collected 181 liver nodules in 156 patients at high risk of HCC who underwent gadoxetic acid-enhanced MRI examinations with following surgical resection from 1st August 2017 to 31st December 2021 as the training set; another 42 liver nodules in 36 patients were prospectively collected from 1st January 2022 to 1st October 2022 as the test set. The time-intensity curves (TICs) of liver nodules were formed with consecutive time points: 0 s, 20 s, 1 min, 2 min, 5 min, 10 min, 15 min, and 20 min since contrast injection. A novel enhancement flux analysis was applied by using a biexponential function fitting to distinguish benignities and HCC. Besides, previously published models including maximum enhancement ratio (ERmax), percentage signal ratio (PSR), and ERmax+PSR were compared. The areas under the receiver operating characteristic curves (AUCs) were compared among these methods. RESULTS: The novel enhancement flux analysis showed the highest AUCs in the training set (0.897, 95%CI: 0.833-0.960) and the test set (0.859, 95%CI: 0.747-0.970) among all models. The AUCs of PSR, ERmax and ERmax+PSR were 0.801 (95%CI: 0.710-0.891), 0.620 (95%CI: 0.510-0.729), and 0.799 (95%CI: 0.709-0.889) in the training set, and were 0.701 (95%CI: 0.539-0.863), 0.529 (95%CI: 0.342-0.717), and 0.708 (95%CI: 0.549-0.867) in the test set. CONCLUSIONS: The biexponential flux analysis for gadoxetic-acid enhanced MRI presents a better potential in accurate diagnosis of small HCC nodules.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Retrospective Studies , Contrast Media , Sensitivity and Specificity , Gadolinium DTPA , Magnetic Resonance Imaging/methods
11.
Nano Lett ; 23(9): 4014-4022, 2023 May 10.
Article En | MEDLINE | ID: mdl-37079652

Lithium metal is widely regarded as the "ultimate" anode for energy-dense Li batteries, but its high reactivity and delicate interface make it prone to dendrite formation, limiting its practical use. Inspired by self-assembled monolayers on metal surfaces, we propose a facile yet effective strategy to stabilize Li metal anodes by creating an artificial solid electrolyte interphase (SEI). Our method involves dip-coating Li metal in MPDMS to create an SEI layer that is rich in inorganic components, allowing uniform Li plating/stripping under a low overpotential over 500 cycles in carbonate electrolytes. In comparison, pristine Li metal shows a rapid increase in overpotential after merely 300 cycles, leading to failure soon after. Molecular dynamics simulations demonstrate that this uniform artificial SEI suppresses Li dendrite formation. We further demonstrated its enhanced stability pairing with LiFePO4 and LiNi1-x-yCoxMnyO2 cathodes, highlighting the proposed strategy as a promising solution for practical Li metal batteries.

12.
Chem Soc Rev ; 52(3): 1103-1128, 2023 Feb 06.
Article En | MEDLINE | ID: mdl-36651148

Energy and environmental issues have attracted increasing attention globally, where sustainability and low-carbon emissions are seriously considered and widely accepted by government officials. In response to this situation, the development of renewable energy and environmental technologies is urgently needed to complement the usage of traditional fossil fuels. While a big part of advancement in these technologies relies on materials innovations, new materials discovery is limited by sluggish conventional materials synthesis methods, greatly hindering the advancement of related technologies. To address this issue, this review introduces and comprehensively summarizes emerging ultrafast materials synthesis methods that could synthesize materials in times as short as nanoseconds, significantly improving research efficiency. We discuss the unique advantages of these methods, followed by how they benefit individual applications for renewable energy and the environment. We also highlight the scalability of ultrafast manufacturing towards their potential industrial utilization. Finally, we provide our perspectives on challenges and opportunities for the future development of ultrafast synthesis and manufacturing technologies. We anticipate that fertile opportunities exist not only for energy and the environment but also for many other applications.

13.
Biochimie ; 208: 38-45, 2023 May.
Article En | MEDLINE | ID: mdl-36473602

The specificity and sensitivity of microRNA (miRNA) detection play a vital role in the early diagnosis of cancer and the treatment of various diseases. Here, we constructed a fluorescent biosensor based on click chemistry-terminal deoxynucleotidyl transferase (ccTdT) combined with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)12a cascade amplification system to achieve ultrasensitive miRNA-21 detection. Target miRNA-21 was employed as a template for click chemistry ligation of two nucleic acid probes, the product of which can be combined with magnetic microbeads (MBs). Then the 3'-end of the ligated nucleic acid and complementary strand miRNA-21 was extended by TdT. The extended poly-T tails activated the trans-cleavage ability of CRISPR/Cas12a, cleaving the reporter gene to generate the fluorescent signal. The proposed biosensor has a wide linear detection range, from 1 pM to 105 pM, with detection limits as low as 88 fM under optimal experimental conditions. Hence, this fluorescent biosensor enables simple, sensitive detection of miRNAs and offers a promising analytical platform for clinical diagnostics and biomedical research.


DNA Nucleotidylexotransferase , MicroRNAs , CRISPR-Cas Systems , Click Chemistry , Coloring Agents , DNA-Directed DNA Polymerase , MicroRNAs/genetics
14.
Environ Sci Pollut Res Int ; 30(15): 42923-42942, 2023 Mar.
Article En | MEDLINE | ID: mdl-35064509

This paper investigates whether emerging digital finance can reduce environmental pollution in China based on data from 273 of China's prefecture-level cities spanning the period from 2010 to 2017. The dynamic spatial econometric models (DSDM) find a significant negative association between digital finance and pollutants emissions, and the impacts vary among regions and urban development stages. The impact mechanism test proves that digital finance reduces pollutants emissions through technological innovation, structural adjustment, and capital allocation effects. In addition, we explore the different dimensions of digital finance and find that the depth of use has a more practical effect on reducing emissions. Further analyses based on the threshold model show an inverted N-shaped nexus between digital finance and emissions. The threshold effect also exists in terms of the traditional financial level. Our study proves that emerging digital finance crucially affects its potential benefits to environment and provides an empirical basis for policy-makers to accelerate the digitalization of financial markets, particularly paying attention to its emission-reduction effects.


Environmental Pollutants , Cities , Environmental Pollution , China , Models, Econometric , Economic Development
15.
Cancers (Basel) ; 14(21)2022 Oct 27.
Article En | MEDLINE | ID: mdl-36358716

Background: A number of studies have reported an association between the dynamics of neutrophil-to-lymphocyte ratio (NLR) and clinical efficacy in patients treated with immune checkpoint inhibitors (ICIs), but there is still a lack of a meta-analysis or systematic review. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched until September 2022 for studies reporting on the association between the change in NLR after ICI treatment and clinical outcomes. Outcome measures of interest included: change in NLR before and after treatment, overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of 4154 patients in 38 studies were included. The pooled percentage of patients with increased NLR was 49.7% (95CI%: 43.7−55.8%). Six studies discussing the change in NLR in patients with different tumor responses all showed that the NLR level in patients without response to immunotherapy may increase after ICI treatment. The upward trend in NLR was associated with shorter OS (pooled HR: 2.05, 95%CI: 1.79−2.35, p < 0.001) and PFS (pooled HR: 1.89, 95%CI: 1.66−2.14, p < 0.001) and higher ORR (pooled OR: 0.27, 95%CI: 0.19−0.39, p < 0.001), and downward trend in NLR was associated with longer OS (pooled HR: 0.49, 95%CI: 0.42−0.58, p < 0.001) and PFS (pooled HR: 0.55, 95%CI: 0.48−0.63, p < 0.001) and lower ORR (pooled OR: 3.26, 95%CI: 1.92−5.53, p < 0.001). In addition, post-treatment high NLR was associated with more impaired survival than baseline high NLR (pooled HR of baseline high NLR: 1.82, 95%CI: 1.52−2.18; pooled HR of post-treatment high NLR: 2.93, 95%CI: 2.26−3.81), but the NLR at different time points may have a similar predictive effect on PFS (pooled HR of baseline high NLR: 1.68, 95%CI: 1.44−1.97; pooled HR of post-treatment high NLR: 2.00, 95%CI: 1.54−2.59). Conclusions: The NLR level of tumor patients after ICI treatment is stable overall, but the NLR level in patients without response to immunotherapy may increase after ICI treatment. Patients with an upward trend in NLR after ICI treatment were associated with worse clinical outcomes; meanwhile, the downward trend in NLR was associated with better clinical outcomes. Post-treatment high NLR was associated with more impaired survival than baseline high NLR.

16.
Anal Bioanal Chem ; 414(29-30): 8437-8445, 2022 Dec.
Article En | MEDLINE | ID: mdl-36264297

This study provides proof of concept of a colorimetric biosensor for influenza H1N1 virus assay based on the CRISPR/Cas13a system and hybridization chain reaction (HCR). Target RNA of influenza H1N1 virus activated the trans-cleavage activity of Cas13a, which cleaved the special RNA sequence (-UUU-) of the probe, further initiating HCR to copiously generate G-rich DNA. Abundant G-quadruplex/hemin was formed in the presence of hemin, thus catalyzing a colorimetric reaction. The colorimetric biosensor exhibited a linear relationship from 10 pM to 100 nM. The detection limit was 0.152 pM. The biosensor specificity was excellent. This new and sensitive detection method for influenza virus is a promising rapid influenza diagnostic test.


Biosensing Techniques , DNA, Catalytic , G-Quadruplexes , Influenza A Virus, H1N1 Subtype , Influenza, Human , Humans , Hemin , DNA, Catalytic/metabolism , Influenza A Virus, H1N1 Subtype/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Influenza, Human/diagnosis , Biosensing Techniques/methods
17.
ACS Omega ; 7(40): 35515-35522, 2022 Oct 11.
Article En | MEDLINE | ID: mdl-36249407

MicroRNAs (miRNAs) play a very important role in biological processes and are used as biomarkers for the detection of a variety of diseases, including neurodegenerative diseases, chronic cardiovascular diseases, and cancers. A sensitive point-of-care (POC) method is crucial for detecting miRNAs. Herein, CRISPR-Cas12a combined with the click chemistry actuated exponential amplification reaction was introduced into an electrochemical biosensor for detecting miRNA-21. The target miRNA-21 initiated the click chemistry-exponential amplification reaction in the electrochemical biosensor to produce numerous nucleic acid fragments, which could stimulate the trans-cleavage ability of CRISPR-Cas12a to cleave hairpin DNA electrochemical reporters immobilized on the electrode surface. Under optimal conditions, the minimum detection limit for this electrochemical biosensor was as low as 1 fM. Thus, the proposed electrochemical biosensor allows sensitive and efficient miRNA detection and could be a potential analysis tool for POC test and field molecular diagnostics.

18.
Small Methods ; 6(11): e2200995, 2022 Nov.
Article En | MEDLINE | ID: mdl-36250994

It is a major challenge to achieve a high-performance anode for sodium-ion batteries (SIBs) with high specific capacity, high rate capability, and cycling stability. Bismuth sulfide, which features a high theoretical specific capacity, tailorable morphology, and low cost, has been considered as a promising anode for SIBs. Nevertheless, due to a lack of direct atomistic observation, the detailed understanding of fundamental intercalation behavior and Bi2 S3 's (de)sodiation mechanisms remains unclear. Here, by employing in situ high-resolution transmission electron microscopy, consecutive electron diffraction coupled with theoretical calculations, it is not only for the first time identified that Bi2 S3 exhibits specific ionic transport pathways preferred to diffuse along the (110) direction instead of the (200) plane, but also tracks their real-time phase transformations (de)sodiation involving multi-step crystallographic tuning. The finite-element analysis further disclosed multi-reaction induced deformation and the relevant stress evolution originating from the combined effect of the mechanical and electrochemical interaction. These discoveries not only deepen the understanding of fundamental science about the microscopic reaction mechanism of metal chalcogenide anodes but also provide important implications for performance optimization.

19.
Bioorg Med Chem Lett ; 74: 128949, 2022 10 15.
Article En | MEDLINE | ID: mdl-35998847

Abnormal microRNA (miRNA) expression levels are confirmed as diagnostic biomarkers of the emergence and development of diseases. In this study, we developed a fluorescence biosensor for detecting miRNAs based on double amplification reactions with the primer exchange reaction (PER) and CRISPR/Cas12a. In the absence of target miRNA-21, PER hairpins remained locked by the protector strands and the primers did not extend. In the presence of target miRNA-21, the miRNA-21 bound to the guard sequence and exposed primer binding sites. Also, the closed PER hairpin was unlocked to specifically extend primers into single-stranded DNA (ssDNA) of unequal lengths. These ssDNAs of unequal lengths could activate the cleavage of a reporter by Cas12a, leading to an increase in detectable fluorescence signals. A large number of short nucleic acid fragments were amplified by PER-CRISPR multiple cycle cleavage fluorescent probes. Based on PER-combined CRISPR/Cas12a established dual signal amplification method was characterized by a low limit of detection of 10fM. The fluorescent biosensor for miRNA detection had the advantages of low detection cost, simple operation, and mobility, providing a very promising platform for the point-of-care testing of miRNA-21.


Biosensing Techniques , MicroRNAs , Biosensing Techniques/methods , CRISPR-Cas Systems/genetics , DNA, Single-Stranded , Fluorescent Dyes/chemistry , MicroRNAs/genetics
20.
Adv Mater ; 34(36): e2202848, 2022 Sep.
Article En | MEDLINE | ID: mdl-35762033

All-solid-state batteries (ASSBs) show great potential as high-energy and high-power energy-storage devices but their attainable energy/power density at room temperature is severely reduced because of the sluggish kinetics of lithium-ion transport. Here a thermally modulated current collector (TMCC) is reported, which can rapidly cold-start ASSBs from room temperature to operating temperatures (70-90 °C) in less than 1 min, and simultaneously enhance the transient peak power density by 15-fold compared to one without heating. This TMCC is prepared by integrating a uniform, ultrathin (≈200 nm) nickel layer as a thermal modulator within an ultralight polymer-based current collector. By isolating the thermal modulator from the ion/electron pathway of ASSBs, it can provide fast, stable heat control yet does not interfere with regular battery operation. Moreover, this ultrathin (13.2 µm) TMCC effectively shortens the heat-transfer pathway, minimizes heat losses, and mitigates the formation of local hot spots. The simulated heating energy consumption can be as low as ≈3.94% of the total battery energy. This TMCC design with good tunability opens new frontiers toward smart energy-storage devices in the future from the current collector perspective.

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