Magnetic Microbead-Based Herringbone Chip for Sensitive Detection of Human Immunodeficiency Virus.

The microfluidic chip-based nucleic acid detection method significantly improves the sensitivity since it precisely controls the microfluidic flow in microchannels. Nonetheless, significant challenges still exist in improving the detection efficiency to meet the demand for rapid detection of trace substances. This work provides a novel magnetic herringbone (M-HB) structure in a microfluidic chip, and its advantage in rapid and sensitive detection is verified by taking complementary DNA (cDNA) sequences of human immunodeficiency virus (HIV) detection as an example. The M-HB structure is designed based on controlling the magnetic field distribution in the micrometer scale and is formed by accumulation of magnetic microbeads (MMBs). Hence, M-HB is similar to a nanopore microstructure, which has a higher contact area and probe density. All of the above is conducive to improving sensitivity in microfluidic chips. The M-HB chip is stable and easy to form, which can linearly detect cDNA sequences of HIV quantitatively ranging from 1 to 20 nM with a detection limit of 0.073 nM. Compared to the traditional herringbone structure, this structure is easier to form and release by controlling the magnetic field, which is flexible and helps in further study. Results show that this chip can sensitively detect the cDNA sequences of HIV in blood samples, demonstrating that it is a powerful platform to rapidly and sensitively detect multiple nucleic acid-related viruses of infectious diseases.

Nearly diffraction-limited picosecond pulse amplification from LMA fluoride fiber at 2.8 µm.

We demonstrated the generation of a nearly diffraction-limited picosecond pulse from a large-mode-area (LMA) fluoride fiber amplifier. Seeded with a mode-locked fiber oscillator at 2.8 µm, the LMA Er:ZBLAN fiber amplifier delivered the pulse of 16 µJ with a duration of 70 ps at 5 kHz. The nearly diffraction-limited beam was obtained from the 50 µm LMA fiber using the fundamental mode excitation technique, with a measured M2 value of 1.25 for x axis and 1.27 for y axis, respectively. This high-beam-quality high-energy picosecond fiber-based system of 2.8 µm exhibits a great potential in the high-precision biomaterial processing.

Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/ß-catenin signalling pathway.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Chiroptical-responsive nanoprobe for the optosensing of chiral amino acids.

A supersensitive chiroptical-responsive system of enantioselectively recognizing L- and D-tryptophan (Trp) based on ( +)-diacetyl-L-tartaric anhydride-functionalized 1,3,5-triformylphloroglucinol (DTA-functionalized Tp) was constructed for the first time. With a high fluorescence quantum yield of 15.2% and fluorescence lifetime of 57.6 µs, DTA-functionalized Tp as both fluorescent and chiral recognition nanoprobe was used for the discrimination of L- and D-Trp with excitation/emission maxima at 330/490 nm within 3 min. The linear range of the fluorescence sensing was 0.002-0.15 µg mL-1, and the detection limit achieved 1.4 ng mL-1. Furthermore, a smartphone was employed as a detector and processor to couple with the chiroptical-responsive nanoprobe for establishing a novel and visual integration system for rapid and real-time detection of chiral amino acids with a detection limit of 13 ng mL-1. The spiked recoveries of L-Trp in two commercially available functional beverages ranged from 86.00 to 118.33% in fluorescence and smartphone-based sensing system. Based on the excellent chiroptical-responsive effects, high stability, and biocompatibility, the chiroptical-responsive nanoprobe was successfully applied to visual optosensing and fluorescence imaging in response to L- and D-Trp in HeLa cells. This discrimination methodology with high sensitivity and enantioselectively shows great potential for in-site visually monitoring chiral amino acids in real food samples and tracking physiological processes.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. METHODS: PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). RESULTS: A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65-0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53-0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53-0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63-0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44-0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23-3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53-2.64, P < 0.001) and hand-foot syndrome (OR = 8.67, 95% CI 6.70-11.22, P < 0.001). CONCLUSION: This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

Extracellular Recording of Entire Neural Networks Using a Dual-Mode Microelectrode Array With 19584 Electrodes and High SNR.

Electrophysiological research on neural networks and their activity focuses on the recording and analysis of large data sets that include information of thousands of neurons. CMOS microelectrode arrays (MEAs) feature thousands of electrodes at a spatial resolution on the scale of single cells and are, therefore, ideal tools to support neural-network research. Moreover, they offer high spatio-temporal resolution and signal to-noise ratio (SNR) to capture all features and subcellular resolution details of neuronal signaling. Here, we present a dual-mode (DM) MEA, which enables simultaneous: 1) full-frame readout from all electrodes and 2) high-SNR readout from an arbitrarily selectable subset of electrodes. The DM-MEA includes 19584 electrodes, 19584 full-frame recording channels with noise levels of 10.4 µVrms in the action potential (AP) frequency band (300 Hz-5 kHz), 246 low-noise recording channels with noise levels of 3.0 µVrms in the AP band and eight stimulation units. The capacity to simultaneously perform full-frame and high-SNR recordings endows the presented DM-MEA with great flexibility for various applications in neuroscience and pharmacology.

An ionic liquid-assisted quantum dot-grafted covalent organic framework-based multi-dimensional sensing array for discrimination of insecticides using principal component analysis and clustered heat map.

A robust multi-dimensional sensing array based on VBimBF4B/MAA-anchored quantum dot (QD)-grafted covalent organic frameworks (COFs) [(V-M)/QD-grafted COFs] was established via one-pot strategy. The multi-dimensional sensing array has the outstanding advantages of physicochemical and thermal stability, large specific surface area, and regular pore structures. The assistance of ionic liquid VBimBF4B enhanced the transduction efficiency, and the synergistic effect of COFs enhanced detection efficiency. The improved multi-dimensional sensing array by COFs and ionic liquid VBimBF4B served to identify seven insecticides by non-specific interactions via hydrogen bonding, and the differences in the kinetics of the binding to the insecticides resulted in variation of the three-output channel (fluorescence, phosphorescence, and light scattering) signals, thus generating a distinct optical fingerprint. The unique fingerprint patterns of seven kinds of common insecticides at 200 µg L-1 were successfully discriminated using principal component analysis and clustered heat map analysis. The multi-dimensional sensing array showed a response to seven insecticides based on three spectral channels over the range of 0.001-0.4 µg mL-1 with a limit of detection of 1.08-18.68 µg L-1. The spiked recovery of tap water was 79.86-134.22%, with RSD ranging from 0.89-14.9%. This study broadens the applications of sensing arrays technology and provides a promising building block for insecticide determination.

Evaluation of Polycyclic Aromatic Hydrocarbons (PAHs) in Bamboo Shoots from Soil.

The toxicity, carcinogenicity and persistence of polycyclic aromatic hydrocarbons (PAHs) pose a great threat to the ecological system and human health. The contamination levels, translocation and source analysis of 16 PAHs in bamboo shoot and its planted soil were investigated. The average concentrations of total PAHs were 18.80 ± 1.90 µg/kg and 123.98 ± 113.36 µg/kg in bamboo shoots and soils, respectively. The most abundant PAH was Phenanthrene (PHE), with the detected average concentrations of 5.85 µg/kg in bamboo shoots and 19.28 µg/kg in soils. The highest detected types of PAHs were 3 rings and 4 rings, with the proportions of 80.69% (bamboo shoots) and 35.23% (soils). The transfer factors of PAHs were ranged from 0.011 to 0.895, in which PAHs with 3 rings showed the strongest transfer ability. The combustion of biomass and petroleum might be the main source of PAHs in the planted soils of bamboo shoots.

Prognostic factors in patients with persistent/recurrent differentiated thyroid carcinoma after comprehensive treatment

Objective: To investigate the prognostic factors of patients with persistent/recurrent differentiated thyroid carcinoma (DTC) especially with external invasive persistent recurrent DTC after comprehensive treatment. Methods: The clinical data of 525 patients with persistent/recurrent DTC who underwent surgical treatment from August 2011 to June 2021 in the Department of Head and Neck Surgery of Jiangsu Cancer Hospital were retrospectively analyzed. The prognostic factors affecting overall survival (OS) and relapse-free survival (RFS) of persistent/recurrent DTC, especially external invasive persistent/recurrent DTC were analyzed. Results: Among 525 patients, 318 patients underwent thyroidectomy, 359 patients underwent central lymph node dissection, and 409 patients underwent lateral cervical lymph node dissection. Among 493 followed-up patients, 5-year OS and RFS were 95.10% and 89.60%, 8-year OS and RFS were 91.80% and 81.30%. Cox regression analysis showed that in patients with persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence, male gender and distant metastasis were independent risk factors of OS (all P<0.05); while the simultaneous invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (all P<0.05). In patients with external invasive persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence and male gender were independent risk factors of OS (both P<0.05); while multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (both P<0.05). Conclusions: Male patients aged 55 years old and above, with distant metastasis have a higher risk of poorer prognosis in persistent/recurrent DTC; while patients with simultaneous external invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 are more likely to relapse. For external invasive persistent/recurrent DTC, male patients aged 55 years old and above have a higher risk of poorer prognosis; while patients with multiple organ invasion and the number of previous operations ≥2 are more likely to have recurrence.

Determination of nereistoxin-related insecticide via quantum-dots-doped covalent organic frameworks in a molecularly imprinted network.

Quantum-dots-doped covalent organic frameworks in a molecularly imprinted network (QDs-doped COFs@MIP) were developed for detection of nereistoxin (NRT)-related insecticide in tap water. The preparation of QDs-doped COFs@MIP was easy to accomplish via one-pot synthesis at room temperature. QDs-doped COFs@MIP quenched by targeting thiosultap due to the photoinduced charge transfer. A Brunauer-Emmett-Teller surface area of 186.20 m2 g-1 and a maximum adsorption capacity of 771 mg g-1 of the QDs-doped COFs@MIP exhibited good selectivity and adsorption capacity. Direct fluorescence determination was established over the range 5-100 µg L-1 (R2 = 0.9959) with a detection limit of 1.60 µg L-1. Furthermore, 86.5-106.5% recoveries of spiked tap water were achieved. The determination system was feasible for tracing the NRT-related insecticide with high accuracy and good repeatability and reproducibility. Graphical abstract .

A comparison between triplet and doublet chemotherapy in improving the survival of patients with advanced gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Chemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer. METHODS: RCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity. RESULTS: Our analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69-0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86-0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12-1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66-0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57-0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69-0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42-1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47-1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81-1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82-1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81-0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86-1.07; P = 0.47) that among Asian patients. CONCLUSIONS: Compared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.

One-pot isothermal amplification permits recycled activation of CRISPR/Cas12a for sensing terminal deoxynucleotidyl transferase activity.

This study introduces a one-pot isothermal amplification assay for ultrasensitive analysis of terminal deoxynucleotidyl transferase (TdT) activity. The system realizes recycled activation of CRISPR/Cas12a, enabling exceptional signal amplification. This approach maximizes the simplicity of the detection method, offering a promising avenue for molecular disease diagnosis.

An allosteric palindromic hairpin probe based dual-mode interactive strand displacement amplification enables robust miRNA biosensing.

This study introduces an allosteric palindromic hairpin probe (APHP)-based dual-mode interactive strand displacement amplification (DMI-SDA) system for ultrasensitive detection of microRNA-155. The system achieves exceptional signal amplification and improved signal preservation using dimeric G-triplexes as signal reporters, enabling robust detection of miRNA-155, representing a promising avenue in molecular diagnosis.

Ultrasimple size encoded microfluidic chip for rapid simultaneous multiplex detection of DNA sequences.

Simultaneous multiplexed analysis can provide comprehensive information for disease diagnosis. However, the current multiplex methods rely on sophisticated barcode technology, which hinders its wider application. In this study, an ultrasimple size encoding method is proposed for multiplex detection using a wedge-shaped microfluidic chip. Driving by negative pressure, microparticles are naturally arranged in distinct stripes based on their sizes within the chip. This size encoding method demonstrates a high level of precision, allowing for accuracy in distinguishing 3-5 sizes of microparticles with a remarkable accuracy rate of up to 99%, even the microparticles with a size difference as small as 0.5 µm. The entire size encoding process is completed in less than 5 min, making it ultrasimple, reliable, and easy to operate. To evaluate the function of this size encoding microfluidic chip, three commonly co-infectious viruses' nucleic acid sequences (including complementary DNA sequences of HIV and HCV, and DNA sequence of HBV) are employed for multiplex detection. Results indicate that all three DNA sequences can be sensitively detected without any cross-interference. This size-encoding microfluidic chip-based multiplex detection method is simple, rapid, and high-resolution, its successful application in serum samples renders it highly promising for potential clinical promotion.

Integrating recombinase polymerase amplification with CRISPR/Cas9-initiated nicking-rolling circle amplification in Staphylococcus aureus assay.

We integrate recombinase polymerase amplification (RPA) with CRISPR/Cas9-initiated nicking rolling circle amplification (CRISPR/Cas9-nRCA) for detecting Staphylococcus aureus. This approach utilizes a unique dimeric G-triplex structure, demonstrating firstly enhanced ThT fluorescence for target detection. The proof-of-concept study introduces a new avenue for integrating isothermal amplifications with CRISPR/Cas9 in the fields of pathogen detection and disease diagnosis.

Magnetically driven nanorobots based on peptides nanodots with tunable photoluminescence for rapid scavenging reactive α-dicarbonyl species and effective blocking of advanced glycation end products.

The present work constructed magnetically driven nanorobots by conjugating the photoluminescent ß-alanine-histidine (ß-AH) nanodots to superparamagnetic nanoparticles (SPNPs) for simultaneously sensitive determination and fast trapping RDS in food processing, achieving efficient regulation of advanced glycation end products (AGEs) risk. Bio-derivative ß-AH nanodots with orderly self-assembly nanostructure and tunable photoluminescent properties served as both biorecognition elements to effectively bind and scavenge the reactive α-dicarbonyl species (RDS), as well as the indicator with sensitive fluorescence response in the food matrix. The magnetically driven nanorobots with excellent biosafety of endogenous dipeptides displayed a high binding capacity of 80.12 mg g-1 with ultrafast equilibrium time. Furthermore, the magnetically driven nanorobots achieved rapid removal of the RDS with the manipulation of the external magnetic field, which enabled intercepting AGEs generation without byproducts residual as well as ease-of-operation. This work provided a promising strategy with biosafety and versatility for both accurate determination and efficient removal of hazards.

Dandelion-like covalent organic frameworks with high-efficiency fluorescence for ratiometric sensing and visual tracking-by-detection of Fe3.

Iron ions, one of the most common heavy metal pollutants in industrial waste materials, are continuously actively or passively delivered to the environment. Meanwhile, the importance of Fe3+ in biological processes in vivo can not be neglected due to its crucial role in maintaining normal physiological function. Therefore, a ratiometric fluorescence covalent organic framework (TD-COF) was constructed for tracking-by-detection of Fe3+. Alkynes-extended 1,3,6,8-tetrakis(4-ethynyl benzaldehyde)-pyrene (TEBPY) with complete planar structure and 2,5-dihydroxyterephthalohydrazide (DHTH) with functional group -OH were selected as the building blocks. The ratiometric fluorescence TD-COF with a dandelion-like structure exhibited its dual emission peaked at 510 nm and 630 nm. It displayed an obvious fluorescence color variation of yellow-red-black in the presence of Fe3+. Benefiting from the high luminescent efficiency (QY of 36.4%) and multiple identical binding sites, TD-COF exhibited a wide linear range to Fe3+ (0.005-50 µM) with a detection limit of 10.9 nM. Additionally, a smartphone visual sensing platform integrated with TD-COF was developed based on the color transformation and successfully applied to visual smart real-time monitoring Fe3+. More surprisingly, the maximum adsorption capacity of TD-COF towards Fe3+ was 833.3 mg/g due to the coordination interaction and cationic π-effect. The practicability of the smartphone-integrated ratiometric sensing platform for visual tracking-by-detection of Fe3+ was verified by choosing tap water as the actual sample, and the recoveries were calculated to be 98.71-100.88%. This work thus developed COF-based ratiometric sensing of Fe3+, which is an attractive candidate for further application in fluorescent sensing and visual monitoring.

Magnetically Controlled Nanorobots Based on Red Emissive Peptide Dots and Artificial Antibodies for Specific Recognition and Smart Scavenging of Nε-(Carboxymethyl)lysine in Dairy Products.

Food-borne advanced glycation end products (AGEs) are highly related to various irreversible diseases, and Nε-(carboxymethyl)lysine (CML) is the typical hazardous AGE. The development of feasible strategies to monitor and reduce CML exposure has become desirable to address the problems. In this work, we proposed magnetically controlled nanorobots by integrating an optosensing platform with specific recognition and binding capability, realizing specific anchoring and accurate determination as well as efficient scavenging of CML in dairy products. The artificial antibodies offered CML imprinted cavities for highly selective absorption, and the optosensing strategy was designed based on electron transfer from red emissive self-assembling peptide dots (r-SAPDs) to CML, which was responsible for the identity, response, and loading process. The r-SAPDs overcame the interference from autofluorescence, and the limit of detection was 0.29 µg L-1, which bestowed accuracy and reliability for in situ monitoring. The selective binding process was accomplished within 20 min with an adsorption capacity of 23.2 mg g-1. Through an external magnetic field, CML-loaded nanorobots were oriented, moved, and separated from the matrix, which enabled their scavenging effects and reusability. The fast stimuli-responsive performance and recyclability of the nanorobots provided a versatility strategy for effective detection and control of hazards in food.

Atomic coordination structural dynamic evolution of single-atom Mo catalyst for promoting H2 activation in slurry phase hydrocracking.

Development of efficient catalysts with high atomic utilization and turnover frequency (TOF) for H2 activation in slurry phase hydrocracking (SPHC) is crucial for the conversion of vacuum residue (VR). Herein, for the first time, we reported a robust and stable single atoms (SAs) Mo catalyst through a polymerization-pyrolysis-in situ sulfurization strategy for activating H2 in SPHC of VR. An interesting atomic coordination structural dynamic evolution of Mo active sites was discovered. During hydrocracking of VR, the O atoms that coordinated with Mo were gradually replaced by S atoms, which led to the O/S exchange process. The coordination structure of the Mo SAs changed from pre-reaction Mo-O3S1 to post-reaction Mo-O1S3 coordination configurations, promoting the efficient homolytic cleavage activation of H2 into H radical species effectively. The evolved Mo SAs catalyst exhibited robust catalytic hydrogenation activity with the per pass conversion of VR of 65 wt%, product yield of liquid oils of 93 wt%, coke content of only 0.63 wt%, TOF calculated for total metals up to 0.35 s-1, and good cyclic stability. Theoretical calculation reveals that the significant variation of occupied Mo 4d states before and after H2 interaction has a direct bearing on the dynamic evolution of Mo SAs catalyst structure. The lower d-band center of Mo-O1S3 site indicates that atomic H diffusion is easy, which is conducive to catalytic hydrogenation. The finding of this study is of great significance to the development of high atom economy catalysts for the industrial application of heavy oil upgrading technology.

An automated method for precise axon reconstruction from recordings of high-density micro-electrode arrays.

Objective:Neurons communicate with each other by sending action potentials (APs) through their axons. The velocity of axonal signal propagation describes how fast electrical APs can travel. This velocity can be affected in a human brain by several pathologies, including multiple sclerosis, traumatic brain injury and channelopathies. High-density microelectrode arrays (HD-MEAs) provide unprecedented spatio-temporal resolution to extracellularly record neural electrical activity. The high density of the recording electrodes enables to image the activity of individual neurons down to subcellular resolution, which includes the propagation of axonal signals. However, axon reconstruction, to date, mainly relies on manual approaches to select the electrodes and channels that seemingly record the signals along a specific axon, while an automated approach to track multiple axonal branches in extracellular action-potential recordings is still missing.Approach:In this article, we propose a fully automated approach to reconstruct axons from extracellular electrical-potential landscapes, so-called 'electrical footprints' of neurons. After an initial electrode and channel selection, the proposed method first constructs a graph based on the voltage signal amplitudes and latencies. Then, the graph is interrogated to extract possible axonal branches. Finally, the axonal branches are pruned, and axonal action-potential propagation velocities are computed.Main results:We first validate our method using simulated data from detailed reconstructions of neurons, showing that our approach is capable of accurately reconstructing axonal branches. We then apply the reconstruction algorithm to experimental recordings of HD-MEAs and show that it can be used to determine axonal morphologies and signal-propagation velocities at high throughput.Significance:We introduce a fully automated method to reconstruct axonal branches and estimate axonal action-potential propagation velocities using HD-MEA recordings. Our method yields highly reliable and reproducible velocity estimations, which constitute an important electrophysiological feature of neuronal preparations.