Proteoform-Resolved Profiling of Plasminogen Activation Reveals Novel Abundant Phosphorylation Site and Primary N-Terminal Cleavage Site.

Plasminogen (Plg), the zymogen of plasmin (Plm), is a glycoprotein involved in fibrinolysis and a wide variety of other physiological processes. Plg dysregulation has been implicated in a range of diseases. Classically, human Plg is categorized into two types, supposedly having different functional features, based on the presence (type I) or absence (type II) of a single N-linked glycan. Using high-resolution native mass spectrometry, we uncovered that the proteoform profiles of human Plg (and Plm) are substantially more extensive than this simple binary classification. In samples derived from human plasma, we identified up to 14 distinct proteoforms of Plg, including a novel highly stoichiometric phosphorylation site at Ser339. To elucidate the potential functional effects of these post-translational modifications, we performed proteoform-resolved kinetic analyses of the Plg-to-Plm conversion using several canonical activators. This conversion is thought to involve at least two independent cleavage events: one to remove the N-terminal peptide and another to release the active catalytic site. Our analyses reveal that these processes are not independent but are instead tightly regulated and occur in a step-wise manner. Notably, N-terminal cleavage at the canonical site (Lys77) does not occur directly from intact Plg. Instead, an activation intermediate corresponding to cleavage at Arg68 is initially produced, which only then is further processed to the canonical Lys77 product. Based on our results, we propose a refined categorization for human Plg proteoforms. In addition, we reveal that the proteoform profile of human Plg is more extensive than that of rat Plg, which lacks, for instance, the here-described phosphorylation at Ser339.

Optimizing the extraction of active components from Salvia miltiorrhiza by combination of machine learning models and intelligent optimization algorithms and its correlation analysis of antioxidant activity.

We extracted Sal B and TIIA from Salvia miltiorrhiza using enzymatic-assisted ethanol extraction. ACONN predicted optimal process conditions. Enzymolysis and alcohol extraction were used, optimizing conditions and evaluating antioxidant activity. ACONN analyzed data and ACO optimized conditions. Lab verification comprehensively evaluated the conditions. The correlation between Sal B, TIIA, and their antioxidant activities was examined. Weights of 0.5739 and 0.4260 evaluated Sal B and TIIA. ACONN had a 97.46% fitting degree. Optimized extraction conditions improved yield and quality, yielding a comprehensive evaluation value of 27.69 with 4.46% average errors. This approach enhances extraction and compound quality. Antioxidant activity strongly correlated with component yield, influenced by extraction conditions. ACONN-optimized extraction improved Sal B and TIIA yield and quality, with potential as natural antioxidants. Integrating machine learning and optimization algorithms in industrial extraction enhances efficiency and environmental preservation.

Determination and Characterization of Gold Nanoparticles in Liquor Using Asymmetric Flow Field-Flow Fractionation Hyphenated with Inductively Coupled Plasma Mass Spectrometry.

The EU has approved the usage of gold as a food additive (E175) and it has been applied in numerous foods for coloring and decoration purposes. Different from the general assumption that edible gold is mainly present in the form of flakes or external coating in foods, this work demonstrated that gold nanoparticles (Au NPs) can be released from gold flakes and extracted under optimized conditions. To support future risk assessment associated with the exposure of Au NPs to human health, an effective approach was established in this study for both size characterization and mass determination of Au NPs released in a commercial gold-containing liquor using Asymmetric Flow Field-flow Fractionation (AF4) hyphenated with Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Our results showed that no Au NPs were detected in the original liquor product and only after ultrasonication for several minutes did Au NPs occur in the ultrasound-treated liquor. Particularly, Au NPs released in the liquor can be well extracted after 100-fold enrichment of gold flakes and the subsequent ultrasonication for 25 min. Size characterization of Au NPs was conducted by AF4-ICP-MS under calibration with Au NP standards. The gold particle sizes detected ranged from 8.3-398.0 nm and the dominant size of the released Au NPs was around 123.7 nm in the processed liquor. The mass concentration of gold particles determined in the liquor sample with gold flakes concentrated and subsequently sonicated was 48.1 µg L-1 by pre-channel calibration and the overall detection recoveries ranged over 82-95%. For the comparison control samples without ultrasonication, there was no detection of Au NPs. The established method was demonstrated to be useful for monitoring Au NPs in liquor and is possibly applied to other similar foodstuffs.

Single-cell RNA sequencing reveals enhanced antitumor immunity after combined application of PD-1 inhibitor and Shenmai injection in non-small cell lung cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have altered the clinical management of non-small cell lung cancer (NSCLC). However, the low response rate, severe immune-related adverse events (irAEs), and hyperprogressive disease following ICIs monotherapy require attention. Combination therapy may overcome these limitations and traditional Chinese medicine with immunomodulatory effects provides a promising approach. Shenmai injection (SMI) is a clinically effective adjuvant treatment for cancer with chemotherapy and radiotherapy. Therefore, the combined effects and mechanisms of SMI and programmed death-1 (PD-1) inhibitor against NSCLC was focused on this study. METHODS: A Lewis lung carcinoma mouse model and a lung squamous cell carcinoma humanized mouse model were used to investigate the combined efficacy and safety of SMI and PD-1 inhibitor. The synergistic mechanisms of the combination therapy against NSCLC were explored using single-cell RNA sequencing. Validation experiments were performed using immunofluorescence analysis, in vitro experiment, and bulk transcriptomic datasets. RESULTS: In both models, combination therapy alleviated tumor growth and prolonged survival without increasing irAEs. The GZMAhigh and XCL1high natural killer (NK) cell subclusters with cytotoxic and chemokine signatures increased in the combination therapy, while malignant cells from combination therapy were mainly in the apoptotic state, suggesting that mediating tumor cell apoptosis through NK cells is the main synergistic mechanisms of combination therapy. In vitro experiment confirmed that combination therapy increased secretion of Granzyme A by NK cells. Moreover, we discovered that PD-1 inhibitor and SMI combination blocked inhibitory receptors on NK and T cells and restores their antitumoral activity in NSCLC better than PD-1 inhibitor monotherapy, and immune and stromal cells exhibited a decrease of angiogenic features and attenuated cancer metabolism reprogramming in microenvironment of combination therapy. CONCLUSIONS: This study demonstrated that SMI reprograms tumor immune microenvironment mainly by inducing NK cells infiltration and synergizes with PD-1 inhibitor against NSCLC, suggested that targeting NK cells may be an important strategy for combining with ICIs. Video Abstract.

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator.

The AMP-activated protein kinase (AMPK) αßγ heterotrimer is a primary cellular energy sensor and central regulator of energy homeostasis. Activating skeletal muscle AMPK with small molecule drugs improves glucose uptake and provides an opportunity for new strategies to treat type 2 diabetes and insulin resistance, with recent genetic and pharmacological studies indicating the α2ß2γ1 isoform combination as the heterotrimer complex primarily responsible. With the goal of developing α2ß2-specific activators, here we perform structure/function analysis of the 2-hydroxybiphenyl group of SC4, an activator with tendency for α2-selectivity that is also capable of potently activating ß2 complexes. Substitution of the LHS 2-hydroxyphenyl group with polar-substituted cyclohexene-based probes resulted in two AMPK agonists, MSG010 and MSG011, which did not display α2-selectivity when screened against a panel of AMPK complexes. By radiolabel kinase assay, MSG010 and MSG011 activated α2ß2γ1 AMPK with one order of magnitude greater potency than the pan AMPK activator MK-8722. A crystal structure of MSG011 complexed to AMPK α2ß1γ1 revealed a similar binding mode to SC4 and the potential importance of an interaction between the SC4 2-hydroxyl group and α2-Lys31 for directing α2-selectivity. MSG011 induced robust AMPK signalling in mouse primary hepatocytes and commonly used cell lines, and in most cases this occurred in the absence of changes in phosphorylation of the kinase activation loop residue α-Thr172, a classical marker of AMP-induced AMPK activity. These findings will guide future design of α2ß2-selective AMPK activators, that we hypothesise may avoid off-target complications associated with indiscriminate activation of AMPK throughout the body.

Double Network Physical Crosslinked Hydrogel for Healing Skin Wounds: New Formulation Based on Polysaccharides and Zn2.

Developing convenient, efficient, and natural wound dressings remain the foremost strategy for treating skin wounds. Thus, we innovatively combined the semi-dissolved acidified sol-gel conversion method with the internal gelation method to fabricate SA (sodium alginate)/CS (chitosan)/Zn2+ physically cross-linked double network hydrogel and named it SA/CS/Zn2+ PDH. The characterization results demonstrated that increased Zn2+ content led to hydrogels with improved physical and chemical properties, such as rheology, water retention, and swelling capacity. Moreover, the hydrogels exhibited favorable antibacterial properties and biocompatibility. Notably, the establishment of an in vitro pro-healing wound model further confirmed that the hydrogel had a superior ability to repair wounds and promote skin regeneration. In future, as a natural biomaterial with antimicrobial properties, it has the potential to promote wound healing.

Identification and quantification of common microplastics in table salts by a multi-technique-based analytical method.

Microplastics (MPs) are considered as contaminants of emerging concern to the environment and our food chains in recent years. In this study, we presented a multi-technique-based analytical method for detection of MPs through a combination of microscope-FTIR (µ-FTIR) with pyrolysis-GC/MS (Py-GC/MS) to achieve 3-dimensional (3D) information for the identification of polymer type, characterization of particle size and morphology, and quantification of MPs based on both particle number and mass of plastics. Plastics that are commonly used and disposed of, including polyethylene (PE), polypropylene (PP), polystyrene (PS), polyethylene terephthalate (PET), poly vinyl chloride (PVC), polyamide (PA), and poly(methyl methacrylate) (PMMA), were covered in this study. Sample extraction and separation procedures were optimized for these microplastics in table salts where good recoveries (> 75%) were achieved. To further enhance the detection sensitivity in simultaneous quantification of multiple polymers in a sample, a serial dissolution approach with different solvents was developed for the detection of all 7 types of plastics. The established sample preparation process and multi-technique-based analytical method were validated with polymer standards in table salts, resulting in satisfactory qualification and quantification for all samples tested. A retail survey of MPs in table salts was conducted with the developed analytical method, revealing that MPs were present in all commercially available table salts. The total number of MP particles varied from 20 to 125 particles/kg and the total mass contents of seven types of plastics ranged from 30 to 530 µg/kg in table salts.

Detection, Identification and Size Distribution of Silver Nanoparticles (AgNPs) in Milk and Migration Study for Breast Milk Storage Bags.

The engineered silver nanoparticles (AgNPs) have been widely used in various food contact materials (FCMs) based on their antibacterial properties. This widespread use of nanosilver has, however, increased the risk of exposure of AgNPs to human due to their migration from FCMs causing a potential hazard present in foods. Therefore, it is important to establish a reliable and practical method for the detection of AgNPs in food matrices to support risk assessment on AgNPs exposure. Taking the examples of milk and AgNPs-containing breast milk storage bags, this study established an approach for size characterization and quantification of AgNPs in milk and evaluated the relevant silver migration, based on enzymatic digestion and the analysis by asymmetric flow field-flow fractionation (AF4) hyphenated with inductively coupled plasma mass spectrometry (ICP-MS) and single particle inductively coupled plasma mass spectrometry (SP-ICP-MS). No migration of AgNPs was found from breast milk storage bags under various simulated storage conditions as well as extreme scenarios. The suitability and reliability of this method were also validated by the determination of multiple parameters, including accuracy, repeatability, limit of detection (LOD), limit of quantification (LOQ), and recovery, for AF4-ICP-MS and SP-ICP-MS, respectively, with good and overall acceptable evaluation results obtained for all. The established and validated approach was demonstrated to be suitable for the characterization and quantitation of AgNPs in milk as well as the analysis of their migration from breast milk storage bags.

Chemodiversity of Dissolved Organic Matter and Its Molecular Changes Driven by Rhizosphere Activities in Fe Ore Tailings Undergoing Eco-Engineered Pedogenesis.

Dissolved organic matter (DOM) plays an important role in soil structure and biogeochemical function development, which are fundamental for the eco-engineering of tailings-soil formation to underpin sustainable tailings rehabilitation. In the present study, we have characterized the DOM composition and its molecular changes in an alkaline Fe ore tailing primed with organic matter (OM) amendment and plant colonization. The results demonstrated that microbial OM decomposition dramatically increased DOM richness and average molecular weight, as well as its degree of unsaturation, aromaticity, and oxidation in the tailings. Plant colonization drove molecular shifts of DOM by depleting the unsaturated compounds with a high value of nominal oxidation state of carbon (NOSC), such as tannin-like and carboxyl-rich polycyclic-like compounds. This may be partially related to their sequestration by secondary Fe-Si minerals formed from rhizosphere-driven mineral weathering. Furthermore, the molecular shifts of DOM may have also resulted from plant-regulated microbial community changes, which further influenced DOM molecules through microbial-DOM interactions. These findings contribute to the understanding of DOM biogeochemistry and ecofunctionality in the tailings during early pedogenesis driven by OM input and pioneer plant/microbial colonization, providing an important basis for the development of strategies and technologies toward the eco-engineering of tailings-soil formation.

An effective approach for size characterization and mass quantification of silica nanoparticles in coffee creamer by AF4-ICP-MS.

Silicon dioxide (SiO2) has been used as a food additive (E551) for decades. However, some safety concerns have been raised recently due to the detection of silica nanoparticles (SiO2 NPs) in a variety of foodstuffs and their unknown long-term health risk to humans. In order for risk assessment to be conducted, it is essential to establish a reliable, valid, and pragmatic method for analysis of SiO2 NPs in foods for estimation of exposure. This paper presents an effective approach for both size characterization and mass quantification of SiO2 NPs in commercial high-fat coffee creamer using asymmetric flow field-flow fractionation (AF4) coupled to inductively coupled plasma mass spectrometry (ICP-MS). SiO2 NPs from coffee creamer were well extracted after cleanup with hexane in a two-phase (hexane vs. water) aqueous environment. Size determination of SiO2 NPs was performed by on-line AF4-ICP-MS based on calibration with monodispersed standards. The dominant primary size of SiO2 NPs in the studied sample was 36.5 nm. The mass percentages of SiO2 NPs (vs. total SiO2) were 18.6% for the dominant primary nano-silica particles by prechannel calibration and 35.7% for total SiO2 NPs (≤ 100 nm) by postchannel calibration, with recoveries of 89-96% for the former and 75% for the latter. The established approach was demonstrated to be efficient and practical for routine analysis of polydispersed SiO2 NPs with wide nano-size distribution in coffee creamer. This method may be extended to monitor the presence of SiO2 NPs in other similar complex food matrices. Graphical abstract.

Discovery of Novel Angiotensin-Converting Enzyme Inhibitory Peptides from Todarodes pacificus and Their Inhibitory Mechanism: In Silico and In Vitro Studies.

In order to rapidly and efficiently excavate antihypertensive ingredients in Todarodes pacificus, its myosin heavy chain was hydrolyzed in silico and the angiotensin-converting enzyme (ACE) inhibitory peptides were predicted using integrated bioinformatics tools. The results showed the degree of hydrolysis (DH) theoretically achieved 56.8% when digested with papain, ficin, and prolyl endopeptidase (PREP), producing 126 ACE inhibitory peptides. By predicting the toxicity, allergenicity, gastrointestinal stability, and intestinal epithelial permeability, 30 peptides were finally screened, of which 21 had been reported and 9 were new. Moreover, the newly discovered peptides were synthesized to evaluate their in vitro ACE inhibition, showing Ile-Ile-Tyr and Asn-Pro-Pro-Lys had strong effects with a pIC50 of 4.58 and 4.41, respectively. Further, their interaction mechanisms and bonding configurations with ACE were explored by molecular simulation. The preferred conformation of Ile-Ile-Tyr and Asn-Pro-Pro-Lys located in ACE were successfully predicted using the appropriate docking parameters. The molecular dynamics (MD) result indicated that they bound tightly to the active site of ACE by means of coordination with Zn(II) and hydrogen bonding and hydrophobic interaction with the residues in the pockets of S1 and S2, resulting in stable complexes. In summary, this work proposed a strategy for screening and identifying antihypertensive peptides from Todarodes pacificus.

Stereoselective metabolism, distribution, and bioaccumulation brof triadimefon and triadimenol in lizards.

In this research, Chinese lizards (Eremias argus) were chosen as laboratory animal to evaluate the stereoselectivity in the processes of metabolism, distribution, and bioaccumulation of triadimefon. A validated chiral high-performance liquid chromatography coupled with triple quadruple mass spectrometry (HPLC-MS/MS) method was developed for determining enantiomers' residues of parent compound triadimefon and its metabolite triadimenol in lizard blood and tissues. Pharmacokinetic results of single-does exposure suggested that S-(+)-triadimefon was metabolized easier than R-(-)-triadimefon, and RR-(+)-triadimenol was the main metabolic product of triadimefon. During the continuous exposure of two dose (40mg/kg(bw)·d and 200mg/kg(bw)·d), enantiomers of triadimefon and triadimenol were detected in all body compartments, with the highest triadimefon concentrations in brain. However, the triadimenol concentrations were not significantly different among the compartments. The concentrations of RS-(+)-triadimenol were negative correlated with concentrations of RR-(+)-triadimenol both in blood (r=-0.775, p=0.024) and liver (r=-0.834, p=0.02) in 200mg/kg(bw)·d group, which indicates that chiral conversion between enantiomers of triadimenol might exist in the metabolic process of triadimefon. In all the processes, the enantiomer fractions (EFs) of R-(-)-triadimefon and RR-(+)-triadimenol were significantly different from their natural ratios, 0.5 and 0.1, respectively, which proved that metabolism, bioaccumulation, and distribution of triadimefon and triadimenol in lizards were enantioselective. These results help enrich and supplement the knowledge of the stereoselective behaviour of triadimefon and triadimenol in reptile.

Chasing the heat: Unraveling urban hyperlocal air temperature mapping with mobile sensing and machine learning.

Many cities face unprecedented high temperatures with increasing extreme events. Heatwaves pose significant health risks, including cardiovascular diseases, heatstroke, and dehydration. Mapping urban near-surface air temperature (Tair) is crucial for understanding thermal exposure and addressing climate change. Previous studies relied on satellite-derived land surface temperature (LST) and stationary monitoring, but high spaio-temporal Tair mapping is still a challenge. This study optimized a mobile sensing scheme using an electric bicycle platform with environmental and image sensors, and deep learning captured local-scale urban factors. A spatio-temporal data fusion model that consisted of three parts, temporal trend extraction, locality analysis, and neighborhood effect analysis, generated hyperlocal Tair maps. The Results from Beijing demonstrated the effectiveness of the framework, achieving the lowest MAE of 0.02 °C. Optimized data collection and the new model achieved accurate temperature predictions and thermal exposure assessment. Efficiency enhanced sensing strategy was also proposed. The study highlights local-scale factors and spatio-temporal dependencies in addressing heatwaves and climate change impacts in urban areas.

An optimized multi-technique based analytical platform for identification, characterization and quantification of nanoplastics in water.

Nanoplastics (NPs) have been identified as an emerging concern for the environment and our food chains in recent years. Monitoring the concentration and size of nanoplastics is essential to assess the potential risks that nanoplastic particles may pose. In this study, we presented a multi-technique based analytical platform to identify, characterize and quantify nanoplastics in water samples through a combination of sample pre-concentration, asymmetric flow field-flow fractionation coupled with multi-angle light scattering (AF4-MALS) and pyrolysis-GC/MS (Py-GC/MS). Models for predicting NPs concentration and particle number in unknown samples were established and validated using NPs standards of known size and AF4-MALS response. Py-GC/MS was applied for further identification of polymer type and quantification of mass concentration. Filtration conditions for pre-concentration were optimized to ensure a high recovery rate with minimal effect on original particle size. The addition of 0.05% SDS prior to filtration, using controlled filtration procedures, effectively improved the recovery. Furthermore, this study demonstrates the application of the analytical platform for the characterization and quantification of different nanoparticles (e.g. spiked PMMA and PS NPs) in the size range 60 nm-350 nm with detection limits down to 0.01 ppm in water samples. The established analytical platform can fill an analytical gap by offering a solution for quantifying size-resolved mass concentrations of nanoplastics and providing comprehensive data on size distribution, particle number and mass quantification with high sensitivity for detection.

Asymmetric chitosan-derivative/carboxymethylcellulose layer-by-layer film combining antimicrobial and vascular regeneration for the repair of infected wounds.

Bacterially infected wounds are a serious threat to patients' lives and health, and multifunctional dressings with antimicrobial properties and healing promotion are urgently needed. Thus, we used the cationic and anionic properties of chitosan (CS)-nerol (N) derivative (CSN) and carboxymethylcellulose (CMC) to prepare asymmetric layer-by-layer self-assembled (LBL) composite films (CSN-CMC LBL films) with antibacterial and healing properties using a spin-coating method. SEM images showed that the CSN-CMC LBL films had completely different degrees of roughness at the bottom (hydrophilic layer) and at the top (hydrophobic layer), with the roughness at the top increasing as the number of layers increased. The CSN and CMC were used to prepare asymmetric LBL films via the electrostatic attraction of -COO- and NH3+. In addition, adhesion and water contact angle tests showed that the CSN-CMC LBL films had enhanced tissue adhesion and good hydrophobicity. These materials had excellent antimicrobial activity and good biocompatibility. Importantly, the animal infection model results showed that CSN-CMC-8 LBL films effectively eliminated the infection in vivo, inhibited inflammation, promoted vascular regeneration, accelerated the epithelialization process, and achieved high quality healing. Overall, the CSN-CMC LBL films in this study showed considerable potential for application in infected wound healing.

The detection, characterization, and quantification of dominant degradation products of nisin A and Z in selected dairy products by liquid chromatography-high-resolution mass spectrometry technique.

Nisin, a bacteriocin produced through fermentation using bacterium Lactococcus lactis, has several commercial variants such as nisin A and nisin Z. Nisin serves as a natural preservative with antimicrobial properties in various food products, including dairy and beverages, for extending product shelf life. The efficacy and safety of nisin A as a bacteriocin has been well characterized. However, there is limited evidence regarding the efficacy, stability, and safety of nisin Z as a food preservative, as it has not undergone comprehensive regulatory reviews. In this work, we studied the stability of nisin A and Z in a selection of yogurt drinks and found nisin to be unstable, particularly in fruit-flavored yogurt drinks. Both nisin A and Z could experience significant degradation leading to the nisin parent ion peaks dropping below detectable level before the product's expiry date. Compared with nisin A, the formation of oxidized metabolite nisin Z+O appeared to be the predominant reaction for nisin Z. These findings highlight the need for further scientific research to understand the behavior of nisin Z under different application conditions, which is crucial for assessing the efficacy and safety of nisin Z under these conditions. One potential application of this knowledge is to optimize the formulation of yogurt-based drinks to stabilize nisin Z and sustain its biopreservative function throughout the product's shelf life. Additionally, the current study shows that for the testing of the presence of nisin A or nisin Z, it is imperative to cover both the parent and the main degradant(s) of nisin. This is especially true for nisin Z, for which the regulatory approval status may vary in different markets. As such, the confirmative identification of nisin Z and its key metabolites in commercial products would be essential.

Copper- and copper-N-heterocyclic carbene-catalyzed C-H activating carboxylation of terminal alkynes with CO2 at ambient conditions.

The use of carbon dioxide as a renewable and environmentally friendly source of carbon in organic synthesis is a highly attractive approach, but its real world applications remain a great challenge. The major obstacles for commercialization of most current protocols are their low catalytic performances, harsh reaction conditions, and limited substrate scope. It is important to develop new reactions and new protocols for CO(2) transformations at mild conditions and in cost-efficient ways. Herein, a copper-catalyzed and copper-N-heterocyclic carbene-cocatalyzed transformation of CO(2) to carboxylic acids via C─H bond activation of terminal alkynes with or without base additives is reported. Various propiolic acids were synthesized in good to excellent yields under ambient conditions without consumption of any organometallic or organic reagent additives. This system has a wide scope of substrates and functional group tolerances and provides a powerful tool for the synthesis of highly functionalized propiolic acids. This catalytic system is a simple and economically viable protocol with great potential in practical applications.

Elucidating dynamic cell lineages and gene networks in time-course single cell differentiation.

Single cell RNA sequencing (scRNA-seq) technologies provide researchers with an unprecedented opportunity to exploit cell heterogeneity. For example, the sequenced cells belong to various cell lineages, which may have different cell fates in stem and progenitor cells. Those cells may differentiate into various mature cell types in a cell differentiation process. To trace the behavior of cell differentiation, researchers reconstruct cell lineages and predict cell fates by ordering cells chronologically into a trajectory with a pseudo-time. However, in scRNA-seq experiments, there are no cell-to-cell correspondences along with the time to reconstruct the cell lineages, which creates a significant challenge for cell lineage tracing and cell fate prediction. Therefore, methods that can accurately reconstruct the dynamic cell lineages and predict cell fates are highly desirable. In this article, we develop an innovative machine-learning framework called Cell Smoothing Transformation (CellST) to elucidate the dynamic cell fate paths and construct gene networks in cell differentiation processes. Unlike the existing methods that construct one single bulk cell trajectory, CellST builds cell trajectories and tracks behaviors for each individual cell. Additionally, CellST can predict cell fates even for less frequent cell types. Based on the individual cell fate trajectories, CellST can further construct dynamic gene networks to model gene-gene relationships along the cell differentiation process and discover critical genes that potentially regulate cells into various mature cell types.

3D Printed Integrated Gradient-Conductive MXene/CNT/Polyimide Aerogel Frames for Electromagnetic Interference Shielding with Ultra-Low Reflection.

Construction of advanced electromagnetic interference (EMI) shielding materials with miniaturized, programmable structure and low reflection are promising but challenging. Herein, an integrated transition-metal carbides/carbon nanotube/polyimide (gradient-conductive MXene/CNT/PI, GCMCP) aerogel frame with hierarchical porous structure and gradient-conductivity has been constructed to achieve EMI shielding with ultra-low reflection. The gradient-conductive structures are obtained by continuous 3D printing of MXene/CNT/poly (amic acid) inks with different CNT contents, where the slightly conductive top layer serves as EM absorption layer and the highly conductive bottom layer as reflection layer. In addition, the hierarchical porous structure could extend the EM dissipation path and dissipate EM by multiple reflections. Consequently, the GCMCP aerogel frames exhibit an excellent average EMI shielding efficiency (68.2 dB) and low reflection (R = 0.23). Furthermore, the GCMCP aerogel frames with miniaturized and programmable structures can be used as EMI shielding gaskets and effectively block wireless power transmission, which shows a prosperous application prospect in defense industry and aerospace.

A novel water-soluble chitosan grafted with nerol: Synthesis, characterization and biological activity.

In order to improve the antibacterial activity of chitosan and change its solubility, a novel water-soluble chitosan (CS)-nerol (N) derivative (CS-N) was prepared via Schiff base reaction and grafting reaction. FT-IR, NMR, XRD, TGA and SEM were used to characterize the structure and physicochemical properties, and in vitro antibacterial, antioxidant, and cellular assays were used to test for bioactivity and safety. The results revealed that the C6 hydroxyl group of CS was substituted with N, with a degree of substitution of 38 % for CS-N. Furthermore, compared to CS, CS-N demonstrated superior antibacterial activity against Escherichia coli and Staphylococcus aureus, as well as significant DPPH and ABTS free radical scavenging activity. Most importantly, CS-N did not harm HaCaT cells. In conclusion, this study provides a promising strategy for the design of chitosan derivatives with significant potential for application in pharmaceutical, food and cosmetic applications.