Search

All-solid-state lithium batteries (ASSBs) are considered the most promising next-generation lithium-ion batteries attributed to their flame-resistant safety and high energy density. However, the rigidity and brittleness of inorganic solid-state electrolytes pose as key hurdles for the scale-up of production of ASSBs. In this research, an innovative one-step solvent method is proposed to fabricate a flexible Li3InCl6/poly(tetrafluoroethylene) (PTFE) electrolyte and composite cathode. The water/ethanol solvent serves as not only an emulsion breaker to form a fiber framework from PTFE dispersion but also a medium for the synthesis of Li3InCl6electrolytes. This unique solvent synthetic method promotes infiltration and distribution of the electrolyte in the fiber framework while maintaining clay-like flexibility. The co-sintered electrolyte achieves high-temperature resistance (>200 °C) as well as high ionic conductivity at room temperature (0.38 mS cm–1). On this basis, a composite cathode with high mass loading (11.4 mg cm–2) is achieved by a similar synthetic process. The ASSB assembled with the electrolyte and cathode membrane cycles for 40 times at room temperature with a residual capacity of 61.7%. Both designs exhibit stretchable and environmentally friendly properties, which show great promise for the mass roll-to-roll production of ASSBs.

Tumors have considerable cellular heterogeneity that is impossible to explore with simple cell cultures. Spheroid cultures contain pathophysiological and chemical gradients similar to in vivo tumors and show complex responses to therapeutics, similar to a tumor. Using pulsed isotopic labels, we demonstrate the pronounced differential response of the proteome to the drug Regorafenib, a multikinase inhibitor, in HCT 116 spheroids. Regorafenib treatment of outer spheroids inhibits proteins involved in critical pathways such as mTOR signaling, extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling, and colorectal cancer metastasis signaling, resulting in decreased proliferation and cellular apoptosis. By contrast, analysis of the treated core cells shows upregulation of MAPK1 and KRAS, possibly implicating drug resistance within these late apoptotic cells. Thus, pulsed isotopic labeling enables evaluation of the distinct proteomic responses for cells residing in the different chemical microenvironments of the spheroid. This platform promises great utility in assisting researchers’ predictions of pharmacodynamic therapeutic responses within complex tumors.

AbstractThe environmental and physicochemical characteristics and fungal communities of two batches of Chinese Luzhou-flavored Daqu were investigated during the fermentation stage and storage period. The Daqu was processed on July 1, 2018 and August 1, 2018, and was identified as middle-temperature and middle and high-temperature Daqu, respectively. At the genus level, the dominant fungi were Aspergillus during the fermentation stage and Candida after three months of storage. Principal component analysis (PCA) and the unweighted pair group method with arithmetic mean (UPGMA) analysis revealed that the fungal community could be divided into two primary groups based on the fermentation and storage stages. Each large fungal population could then be divided into two smaller groups according to the batch. Notably, LEfSe [line discriminant analysis (LDA) effect size] analysis did not find any significantly different fungal populations between the two batches. Redundancy analysis showed that during the entire culture stage of two batches of Daqu, water content and fermenting power were positively correlated with Aspergillusand Wickerhamomyces, while water content correlated negatively with Rhizopus. During fermentation, environmental humidity correlated negatively with Wickerhamomycesin the two batches of Daqu. This study increases the theoretical understanding of Daqu preparation, especially function of the storage period and the fungal differences between batches of Daqu. Such information potentially enables the quality control of Daqu in order to improve quality by controlling the fungal community via the processing conditions and the addition of Candida.

Around the world, there is a critical need for sustainable energy storage systems for grid-level stationary energy storage. In the search for such systems, aluminum (Al)-ion batteries have recently attracted considerable attention due to their positive attributes including low cost, high abundance of raw materials, and long cycling life. Among all, chloroaluminate ionic liquid (IL) composed of aluminum chloride (AlCl3) and a Lewis basic organic chloride (XCl) is the most widely employed electrolyte system in Al-ion batteries. In many existing Al-ion battery chemistries, chloroaluminate IL simultaneously functions as a medium for ion transportation and as an electroactive anode material. To provide fundamental insights into designing better performing Al-ion batteries, herein, we performed a systematic investigation of the electrochemical and transport properties of four AlCl3-XCl ILs, where X is EMIM (1-ethyl-3-methylimidazolium), BMIM (1-butyl-3-methylimidazolium), TMAH (trimethylammonium), or TEAH (triethylammonium), using a combination of density functional theory calculations and experimentation. Results show that the electrochemical stability window, ion transference number, conductivity, and ionicity of Lewis acidic chloroaluminate ILs are fundamentally governed by the (i) AlCl3/XCl molar ratio (r), which dictates the concentration of ionic species, and (ii) XCl type, which affects the overall degree of interactions among ionic species.

Programmed cell death protein 1 (PD-1) is one of the coinhibitory checkpoints upon T cell activation, the abnormal expression of which severely threatens host immune modulatation for chronic infection. Thus, fast and sensitive monitoring of PD-1 is of vital importance for early diagnosis and cancer treatment. The current detection methods largely based on enzyme-linked immunosorbent assay (ELISA) require time-consuming incubation and complicated washing steps. Herein, we designed a simple and portable nanofiber paper (NFP)-based fluorescence “off-on” immunosensor for PD-1 rapid determination. Molybdenum disulfide (MoS2) nanosheets modified NFP (MoS2–NFP) was employed for adsorbing and immobilizing CdSe/ZnS quantum dots-antibody (QDs-Ab) complex to construct a ready-to-use fluorescent immunosensor. The fluorescent signal of QDs-Ab was initially quenched by MoS2under the Förster resonance energy transfer (FRET) effect. When the PD-1 target was specifically captured onto NFP by immunization, the QDs-Ab-PD-1 complex was promptly desorbed from the MoS2–NFP surface, resulting in FRET impediment and fluorescence recovery. As an alternative quenching agent, graphene oxide (GO) served as a contrast to investigate NFP-based sensing performance. Owing to superior quenching and desorption efficiency, the MoS2–NFP-based fluorescence immunosensor exhibited nearly 2-fold lower detection limit (85.5 pg/mL) than GO–NFP-based sensor (151 pg/mL) for PD-1 monitoring. Excellent selectivity and satisfactory recovery in PD-1 mouse cell culture supernatant samples were confirmed as well. In addition, the comparable detectability of the MoS2–NFP-based immunosensor was accurately evaluated by a standard PD-1 mouse ELISA kit. This study displayed a simple, rapid, low-cost, and portable point-of-care PD-1 assay, indicating its broad application prospect toward clinical diagnoses.

ABSTRACTThe adaptive capacity of psammophytes to sand burial is crucial for the ecological restoration of coastal dune systems. The responses of Spinifex littoreusto different sand burial depths and levels were examined on the coast of Pingtan Island, Fujian Province, South China. The results indicated that, compared with the control group (CG), sand burial on the S. littoreusstolons had no significant impact on the vertical growth of its conjoint ramets. However, the horizontal growth of S. littoreusstolons was stimulated and significantly increased in half-intense (HI) and complete-intense (CI) sand burial treatments by 24.56% and 40.79%, respectively. Throughout the experiment, about 96% of adventitious roots were observed on the base section of stolons, while no roots in the control group (CG). After 20-day artificial sand burial treatments, the dry weight ratio between stem and leaf of S. littoreuswas decreased in all three sections of stolons, especially for the top sections. Overall, S. littoreuscan adapt to the complete and intense sand burial in growing season by rapid growth of stolons, abundant production of adventitious roots on the stolon base, and more germination of leaves on the stolon top.

Non-invasive imaging of living cells is an advanced technique that is widely used in the life sciences and medical research. We demonstrate a refractive index quantification microscopy (RIQM) that enables label-free studies of glioma cell-substrate contacts involving cell adhesion molecules and the extracellular matrix. This microscopy takes advantage of the smallest available spot created when an azimuthally polarized perfect optical vortex beam (POV) is tightly focused with a first-order spiral phase, which results in a relatively high imaging resolution among biosensors. A high refractive index (RI) resolution enables the RI distribution within neuronal cells to be monitored. The microscopy shows excellent capability for recognizing cellular structures and activities, demonstrating great potential in biological sensing and live-cell kinetic imaging.

Using the unique properties of ultra-high temperature ceramic material, a new kind W-ZrB2alloy was prepared. Compared with pure tungsten (PW), the mechanical properties of W-ZrB2alloy were obviously improved. In particular, the sintered alloy showed complete transgranular fracture morphology, and the originally weak grain boundaries of tungsten were greatly strengthened. From macroscopic fracture to microscopic crystal structure, the strengthening mechanism of ZrB2in tungsten matrix was studied by means of transmission electron microscope and energy spectrum analysis. The decomposition of ZrB2and the structure of its decomposition products had been confirmed. The formation of the second phases of various crystal structures and the distribution of B element on the grain boundaries were the key factors to strengthening mechanism.

Emerging nanomaterials such as nanozymes have recently been applied for the immunoassay-based detection of biomarkers. However, the inferior catalytic activity and low water solubility of nanozymes remain as the major limitations compared to natural enzymes. To overcome these limitations, we successfully synthesized a superior nanozyme with a structure of enriched 2D catalytic interface, namely Nanozyme Nest, which was composed of Fe-based metal–organic frameworks (Fe-MOF) and graphene oxide (GO). Then, we applied it in an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for the detection of benzo[a]pyrene-7,8-diol 9,10-epoxide–DNA adduct (BPDE–DNA), which is a metabolite of benzo[a]pyrene (BP) and used as a typical biomarker of woodsmoke exposure in human blood. The Nanozyme Nest features amplified peroxidase-like catalytic ability from graphene and Fe-MOF due to their large surface area and abundant active sites. By using the proposed Nanozyme Nest-based ultrasensitive ELISA, the BPDE–DNA could be detected at a level as low as 0.268 ng/mL, and the obtained sensitivity was much higher than most of the widely used methods. Our work provides a novel strategy to design ultrasensitive immunosensors with advantages of amplified catalytic activity and improved water solubility compared to classic nanozymes. This illustrates the promising applications of the Nanozyme Nest-based immunosensors in point-of-care settings to conveniently detect exposures and diagnose diseases.

The utilization of hydrogels for DNA/cationic polymer polyplex nanoparticle (polyplex) delivery has significantly advanced gene therapy in tissue regeneration and cancer treatment. However, persistent challenges related to the efficacy and safety of encapsulated polyplexes, stemming from issues such as aggregation, degradation, or difficulties in controlled release during or postintegration with hydrogel scaffolds, necessitate further exploration. Here, we introduce an injectable gene therapy gel achieved by incorporating concentrated polyplexes onto densely packed hydrogel microparticles (HMPs). Polyplexes, when uniformly adhered to the gene therapy gel through reversible electrostatic interactions, can detach from the HMP surface in a controlled manner, contrasting with free polyplexes, and thereby reducing dose-dependent toxicity during transfection. Additionally, the integration of RGD cell adhesion peptides enhances the scaffolding characteristics of the gel, facilitating cell adhesion, migration, and further minimizing toxicity during gene drug administration. Notably, despite the overall transfection efficiency showing average performance, utilizing confocal microscopy to meticulously observe and analyze the cellular states infiltrating into various depths of the gene therapy gel resulted in the groundbreaking discovery of significantly enhanced local transfection efficiency, with primary cell transfection approaching 80%. This phenomenon could be potentially attributed to the granular hydrogel-mediated delivery of polyplex nanoparticles, which revolutionizes the spatial and temporal distribution and thus the “encounter” mode between polyplexes and cells. Moreover, the gene therapy gel’s intrinsic injectability and self-healing properties offer ease of administration, making it a highly promising candidate as a novel gene transfection gel dressing with significant potential across various fields, including regenerative medicine and innovative living materials.

Self-assembly of platinum(II) complex foldamers is an essential approach to fabricate advanced luminescent materials. However, a comprehensive understanding of folding kinetics and their absorption spectra remains elusive. By constructing Markov state models (MSMs) from large-scale molecular dynamics simulations, we reveal that two largely similar dinuclear alknylplatinum(II) terpyridine foldamers, Pt-PEG and Pt-PE with slightly different bridges, exhibit distinctive folding kinetics. Particularly, Pt-PEG bears bridge-dominant, plane-dominant, and cooperative pathways, while Pt-PE only prefers the plane-dominant pathway. Such preference originates from their difference in intrabridge electrostatic interactions, leading to contrastive distributions of metastable states. We also found that the bridge-dominant pathway for Pt-PEG becomes more favorable when lowering the temperature. Interestingly, based on the comprehensive conformation ensembles from our MSMs, we reveal the conformation-dependent absorption spectra of Pt-PEG and Pt-PE. Our theoretical spectra not only align with experimental results but also reveal the contributions of diverse conformations to the overall absorption bands explicitly, facilitating the rational design of stimuli-responsive smart luminescent molecules.

Cancerous cells synthesize most of their lipids de novoto keep up with their rapid growth and proliferation. Fatty acid synthase (FAS) is a key enzyme in the lipogenesis pathway that is upregulated in many cancers and has gained popularity as a druggable target of interest for cancer treatment. The first FAS inhibitor discovered, cerulenin, initially showed promise for chemotherapeutic purposes until it was observed that it had adverse side effects in mice. TVB-2640 (Denifanstat) is part of the newer generation of inhibitors. With multiple generations of FAS inhibitors being developed, it is vital to understand their distinct molecular downstream effects to elucidate potential interactions in the clinic. Here, we profile the lipidome of two different colorectal cancer (CRC) spheroids treated with a generation 1 inhibitor (cerulenin) or a generation 2 inhibitor (TVB-2640). We observe that the cerulenin causes drastic changes to the spheroid morphology as well as alterations to the lipid droplets found within CRC spheroids. TVB-2640 causes higher abundances of polyunsaturated fatty acids (PUFAs) whereas cerulenin causes a decreased abundance of PUFAs. The increase in PUFAs in TVB-2640 exposed spheroids indicates it is causing cells to die via a ferroptotic mechanism rather than a conventional apoptotic or necrotic mechanism.

Here, stretchable hierarchical porous polyurethane fibers were designed, fabricated, and employed as a three-dimensional hierarchical interconnected framework for conductive networks interwoven with silver nanoparticles and carbon nanotubes. The fiber possessed favorable thermal insulation, strain sensing, and electric heating properties. The core–shell layered porous structure of fiber made the fiber have high heat insulation performance (the difference value of temperature |ΔT| = 3.54, 8.9, and 12.7 °C at heating stage temperatures of 35, 50, and 65 °C) and ultrahigh elongation at break (813%). Importantly, after conductive filler decoration, the fiber could exhibit real-time strain-sensing capacities with a high gauge factor. In addition, the fibers could be heated at low voltage, like an electrical heater. The development of flexible, stretchable, and multifunctional porous fibers had great potential applications in intelligent wearable devices for integrated thermal management, strain sensing, and intrinsic self-warming capability.

Molecularly imprinted polymers (MIPs), which are synthesized in the presence of a template, have been widely used as antibody mimics for important applications. Through the combination with a highly sensitive detection scheme such as chemiluminescence and surface-enhanced Raman scattering (SERS), MIP-based sandwich assays have emerged as promising analytical tools for the detection of disease biomarkers. However, so far, MIPs have been used only as target-capturing probes, whereas labeling by other means was needed, which limits the application range. Herein, we present a new approach, called a dual MIP-based plasmonic immunosandwich assay (duMIP-PISA), for the specific and sensitive detection of protein biomarkers in complex biological samples. A C-terminal epitope-imprinted self-assembled gold nanoparticle monolayer-coated glass slide was prepared as a plasmonic substrate for the specific extraction of target protein, while N-terminal epitope-imprinted Raman-responsive Ag@SiO2nanoparticles were prepared as nanotags for the specific labeling of captured protein. The formed MIP–protein–MIP sandwich-like complexes could produce a significantly enhanced SERS signal. The dual MIP-based recognitions ensured high specificity of the assay, while SERS detection provided ultrahigh sensitivity. The duMIP-PISA of neuron-specific enolase (NSE) in human serums was demonstrated, which permitted the differentiation of small cell lung cancer patients from healthy individuals. As compared to regular ELISA, the duMIP-PISA exhibited multiple merits including a simpler procedure, faster speed, lower sample volume requirement, and wider linear range. The approach well demonstrated the great potentials of MIPs and can be easily modified and extended to other protein biomarkers. Therefore, the duMIP-PISA approach holds great promise in many important applications such as disease diagnosis.

We report a new thin film encapsulation structure composited of atomic layer deposition layer and organic wrinkles, which show a 13% improvement in color‐viewing‐angle with no decrease in storage lifetime. We also made a demo with the new TFE film, and shows an excellent flexibility performance, which indicates a great potential in wide viewing‐angle flexible display applications.

After the surface of tungsten (W) alloys were roughened by laser, chemical vapor deposition (CVD) of diamond coatings were deposited on three tungsten substrates of pure W, W-1 wt.% La2O3and W-0.5 wt.% TiC. Under the same growth parameters, the presence of the second phase in the tungsten matrix impeded the growth rate of diamonds, so a completed diamond coating with the thickness of 45 μm and a grain diamond size of 10 μm was obtained only on pure tungsten substrate after running for 10 h. Scanning electron microscopy, X-ray diffraction and Raman spectroscopy tests proved that the obtained diamond coating was compact with a high purity and regular morphology. To verify the chemical and structural stability, the as-obtained diamond-coated tungsten materials were exposed to an ion flux of 1.4 × 1021ions m−2s−1in D plasma for 30 min. After irradiation, neither delamination, dramatic coating failure nor entire erosion of the coating (graphitization) was observed. The diamond coating can be an effective protective layer to stop tungsten atoms from splashing into the plasma.

Molecularly imprinted polymers (MIPs) and aptamers, as effective mimics of antibodies, can overcome only some drawbacks of antibodies. Since they have their own advantages and disadvantages, the combination of MIPs with aptamers could be an ideal solution to produce hybrid alternatives with improved properties and desirable features. Although quite a few attempts have been made in this direction, a facile and controllable approach for the preparation of aptamer–MIP hybrids still remains lacking. Herein, we present a new approach for facile and controllable preparation of aptamer–MIP hybrids for high-specificity and high-affinity recognition toward proteins. An aptamer that can bind the glycoprotein alkaline phosphatase (ALP) with relative weak affinity and specificity was used as a ligand, and controllable oriented surface imprinting was carried out with an in-water self-polymerization system of dopamine. A thin layer of polydopamine was formed to cover the template to an appropriate thickness. After removing the template from the polymer, an aptamer–MIP hybrid with apparently improved affinity and specificity toward ALP was obtained, giving cross-reactivity of 3.2–5.6% and a dissociation constant of 1.5 nM. With this aptamer–MIP hybrid, a plasmonic immunosandwich assay (PISA) was developed. Reliable detection of ALP in human serum by the PISA was demonstrated.

Evidently enhanced red emission efficiency from the solid state of tetraphenylporphyrin derivative was achieved by modification with tetraphenylethene units.

A hybrid non-enzymatic glucose sensor made by incorporating boron doped diamond (BDD) film electrode with nickel (Ni)- encapsulated carbon nanotubes (CNTs) were facilely fabricated. The CNTs were grown directly on BDD films in the presence of pre-sputtered Ni layer as a catalyst by hot-filament chemical vapor deposition. The morphology and composition of the hybrid structure were assessed by scanning electron microscopy and Raman spectroscopy. As Ni layer thickness increased, the CNTs were less covered on the surface and the length of CNTs increased. The Ni particles were encapsulated into a large number of CNTs. Electrochemical results indicated that this hybrid structure significantly improved the electrochemical performance of BDD due to the increased specific surface area and synergistic effect of Ni and CNTs. The optimized glucose sensor revealed two broad linear range of 1.25 uM - 0.49 mM and 0.49 mM- 6.79 mM, with a high sensitivity of 1642.20 uA mM[?]1 cm[?]2 (R2 = 0.9988) and 1374.4 uA mM[?]1 cm[?]2 (R2 = 0.9969) respectively. In addition, the hybrid electrode exhibited a low limit of detection which was 1.0 uM (S/N = 3), and good selectivity and stability.

This study aimed to explore the mechanisms of bridging integrator-3dysregulation, its prognostic value, and related signaling pathways in colorectal cancer . Bioinformatic analysis was performed based on the data from The Cancer Genome Atlas–colorectal cancer and Human Protein Atlas. Colorectal cancer cell lines, LoVo and HT29 cells, were used as in vitrocell model to assess the effect of demethylation on bridging integrator-3expression. Results showed that bridging integrator-3was downregulated in colorectal cancer tissues compared to normal colon and rectum tissues. Heatmap of bridging integrator-3messenger RNA expression, exon expression, and DNA methylation indicated a negative correlation between bridging integrator-3expression and methylation of some CpG sites within the coding sequence. Demethylation treatment significantly increased bridging integrator-3expression in LoVo and HT29 cells. Low bridging integrator-3messenger RNA and exon expression were associated with significantly worse overall survival (P= .015 and .013, respectively). Multivariate analysis confirmed that low bridging integrator-3messenger RNA expression was an independent prognostic factor of unfavorable overall survival (Hazard Ratio (HR) = 1.596, 95% confidence interval: 1.024-2.486; P =.039). High bridging integrator-3DNA methylation was also associated with significantly worse overall survival (P= .013). Kyoto Encyclopedia of Genes and Genomes analysis indicated that the genes correlated with bridging integrator-3(absolute Pearson r≥ 0.3, n = 121) were enriched in sphingolipid signaling pathway, natural killer cell-mediated cytotoxicity, p53 signaling pathway, and apoptosis. Based on these findings, we infer that DNA hypermethylation might be an important mechanism of suppressed bridging integrator-3expression in colorectal cancer . Its low expression is an independent predictor of unfavorable survival in patients with primary colorectal cancer . Bridging integrator-3might act as a tumor suppressor via modulating natural killer cell-mediated cytotoxicity, p53 signaling pathway, and apoptosis.

Assays of glycoproteins hold significant biological importance and clinical values, for which immunoassay has been the workhorse tool. As immunoassays are associated with disadvantages such as poor availability of high-specificity antibodies, limited stability of biological reagents, and tedious procedure, innovative alternatives that can overcome these drawbacks are highly desirable. Plasmonic immunosandwich assay (PISA) has emerged as an appealing alternative to immunoassay for fast and sensitive determination of trace glycoproteins in biosamples. Plasmonic substrates play key roles in PISA, not only in determining the specificity but also in greatly influencing the detection sensitivity. Herein, we report a new type of molecularly imprinted plasmonic substrates for rapid and ultrasensitive PISA assay of trace glycoproteins in complex real samples. The substrates were fabricated from glass slides, first coated with self-assembled monolayer (SAM) of gold nanoparticles (AuNPs) and then molecularly imprinted with organo-siloxane polymer in the presence of template glycoproteins. The prepared molecularly imprinted substrates exhibited not only a significant plasmonic effect but also excellent binding properties, ensuring the sensitivity as well as the specificity of the assay. Alkaline phosphatase (ALP) and α-fetoprotein (AFP), glycoproteins that are routinely used as disease markers in clinical diagnosis, were used as representative targets. The limit of detection (LOD) was 3.1 × 10–12M for ALP and 1.5 × 10–14M for AFP, which is the best among the PISA approaches reported. The sample volume required was only 5 μL, and the total time required was within 30 min for each assay. Specific and ultrasensitive determination of ALP and AFP in human serum was demonstrated. Because many disease biomarkers are glycoproteins, the developed PISA approach holds great promise in disease diagnostics.

The application of X-ray imaging in military, industrial flaw detection, and medical examination is inseparable from the wide application of scintillator materials. In order to substitute for lead, lower costs, and reduce self-absorption, organic–inorganic hybrid lead-free perovskite scintillators are emerging as a new option. In this work, novel (TEA)2Zr1–xTexCl6perovskite microcrystals (MCs) were successfully synthesized by a hydrothermal method, with Te4+doping, which leads to yellow triplet-state self-trapped excitons emission. The emission peak of (TEA)2Zr1–xTexCl6located at 605 nm under X-ray excitation, which was applied to X-ray imaging, shows a clear wiring structure inside the USB connector. The detection limit (DL) of 820 nGyair/s for (TEA)2Zr0.9Te0.1Cl6is well below the dose rate corresponding to a standard medical X-ray diagnosis is 5.5 μGyair/s. This work opens up a new path for organic–inorganic hybrid lead-free scintillators.

Metal halides have shown potential as scintillators for X-ray detection due to their high light yield and ease of synthesis. However, the poor X-ray absorption of these halides has hindered their practical application. Herein, Bi3+ions are introduced into Cs2ZrCl6(CZC) microcrystals by a simple solution method in order to improve the absorption of X-rays. The energy level transitions of Bi3+ions enhanced the photoluminescence and increased the atomic number for better X-ray absorption, with a detection limit of 469 nGyair/s. An X-ray detection system was designed based on the Cs2ZrCl6:Bi3+(CZCB) scintillator, and clear projection images were obtained with a spatial resolution of 15.9 lp/mm. Moreover, the 3D visualization computed tomography (CT) image of a ballpoint pen was successfully reconstructed. All of the results demonstrate that the CZCB microcrystals constitute a new generation of potential scintillators that can be used in X-ray CT imaging.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been used to visualize molecular distributions in various biological samples. While it has succeeded in localizing molecules ranging from metabolites to peptides, quantitative MSI (qMSI) has remained challenging, especially in small biological samples like spheroids. Spheroids are a three-dimensional cellular model system that replicate the chemical microenvironments of tumors. This cellular model has played an important role in evaluating the penetration of drugs to better understand the efficacy of clinical chemotherapy. Therefore, we aim to optimize a method to quantify the distribution of therapeutics in a single spheroid using MALDI-MSI. Studies were performed with the therapeutic irinotecan (IR). The calibration curve showed a linear relationship with a limit of detection (LOD) of 0.058 ng/mm2and R2value at 0.9643. Spheroids treated with IR for different lengths of time were imaged using the optimized method to quantify the drug concentration during the penetration process. With a dosing concentration of 20.6 μM, the concentration of IR at 48 h of treatment was 16.90 μM within a single spheroid. Furthermore, spheroids were divided into different layers by spatial segmentation to be quantified separately. This MALDI-qMSI method is amenable to a wide range of drugs as well as their metabolites. The quantification results show great potential to extend this method to other small biological samples such as organoids for patient derived therapies.

Palate development involves various events, including proliferation, osteogenic differentiation, and epithelial-mesenchymal transition. Disruption of these processes can result in the cleft palate (CP). Mouse embryonic palatal mesenchyme (MEPM) cells are commonly used to explore the mechanism of palatal development and CP. However, the role of the microenvironment in the biological properties of MEPM cells, which undergoes dynamic changes during palate development, is rarely reported. In this study, we investigated whether there were differences between the palatal shelf mesenchyme at different developmental stages. Our results found that the palatal shelves facilitate proliferation at the early palate stage at mouse embryonic day (E) 13.5 and the tendency towards osteogenesis at E15.5, the late palate development stage. And the osteogenic microenvironment, which was mimicked by osteogenic differentiation medium (OIM), affected the biological properties of MEPM cells when compared to the routine medium. Specifically, MEPM cells showed slower proliferation, shorter S phase, increased apoptosis, and less migration distance after osteogenesis. E15.5 MEPM cells were more sensitive than E13.5, showing an earlier change. Moreover, E13.5 MEPM cells had weaker osteogenic ability than E15.5, and both MEPM cells exhibited different Lactate dehydrogenase A (LDHA) and Cytochrome c (CytC) expressions in OIM compared to routine medium, suggesting that glycolysis might be associated with the influence of the osteogenic microenvironment on MEPM cells. By comparing the stemness of the two cells, we investigated that the stemness of E13.5 MEPM cells was stronger than that of E15.5 MEPM cells, and E15.5 MEPM cells were more like differentiated cells than stem cells, as their capacity to differentiate into multiple cell fates was reduced. E13.5 MEPM cells might be the precursor cells of E15.5 MEPM cells. Our results enriched the understanding of the effect of the microenvironment on the biological properties of E13.5 and E15.5 MEPM cells, which should be considered when using MEPM cells as a model for palatal studies in the future.

The detection of cellular responses to drugs is important for biomedical research, but there is a lack of convenient label-free methods to analyze responses at the single cell level. The refractive index is a typical biophysical parameter reflecting the cell status. An optical tweezer system was established to measure the trapping efficiency, which relates to the refractive index. The response of two cancer cell lines and their paclitaxel resistant counterparts were measured using optical tweezers. Cyclin B1 expression, polymerized tubulin and caspase-3 activation were measured, compared and associated with the trapping efficiency. The results show that the trapping efficiency declined sharply when caspase-3 was activated. These results suggest that optical tweezers can be used as an auxiliary method to analyze cellular responses to anti-tumor drugs.