In Vivo Exposure Pathways of Ambient Magnetite Nanoparticles Revealed by Machine Learning-Aided Single-Particle Mass Spectrometry.

Nanosized ultrafine particles (UFPs) from natural and anthropogenic sources are widespread and pose serious health risks when inhaled by humans. However, tracing the inhaled UFPs in vivo is extremely difficult, and the distribution, translocation, and metabolism of UFPs remain unclear. Here, we report a label-free, machine learning-aided single-particle inductively coupled plasma mass spectrometry (spICP-MS) approach for tracing the exposure pathways of airborne magnetite nanoparticles (MNPs), including external emission sources, and distribution and translocation in vivo using a mouse model. Our results provide quantitative analysis of different metabolic pathways in mice exposed to MNPs, revealing that the spleen serves as the primary site for MNP metabolism (84.4%), followed by the liver (11.4%). The translocation of inhaled UFPs across different organs alters their particle size. This work provides novel insights into the in vivo fate of UFPs as well as a versatile and powerful platform for nanotoxicology and risk assessment.

Dose-Dependent Effect on Plant Growth of Exposure to Metal-Organic Framework MIL-101(Cr).

With the increasing use of metal-organic frameworks (MOFs), they will inevitably enter the environment intentionally or unintentionally. However, the effects of MOFs on plant growth are poorly understood. Here, we investigated the effects of exposure of the rhizosphere to MOFs on plant growth. MIL-101(Cr) was selected as a research model due to its commercial availability and wide use. Soybean plants at the two-leaf stage were subjected to various durations (1-7 days) and concentrations (0-1000 mg/L) of exposure in hydroculture with a control group treated with ultrapure water. We found that MIL-101(Cr) had a positive effect on soybean growth at a lower dose (i.e., 200 mg/L); however, at higher doses (i.e., 500 and 1000 mg/L), it exhibited significant toxicity to plant growth, which is evidenced by leaf damage. To investigate the mechanism of this effect, we used Cr as an indicator to quantify, track, and image MIL-101(Cr) in the plant with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Results indicated that MIL-101(Cr) primarily accumulated in the cortex of roots (up to 40 times higher than that in stems), with limited translocation to stems and negligible presence in leaves and cotyledons. In addition, metabolomic analysis of soybeans indicated that low-dose MIL-101(Cr) could increase the sucrose content of soybean roots to promote plant growth, while a high dose could induce lipid oxidation in roots. This study provides valuable insights into the ecological toxicology of MOFs and underscores the importance of assessing their environmental impact for sustainable agricultural practices.

Particle Size Determines the Phytotoxicity of ZnO Nanoparticles in Rice (Oryza sativa L.) Revealed by Spatial Imaging Techniques.

To understand the nanotoxicity effects on plants, it is necessary to systematically study the distribution of NPs in vivo. Herein, elemental and particle-imaging techniques were used to unravel the size effects of ZnO NPs on phytotoxicity. Small-sized ZnO NPs (5, 20, and 50 nm) showed an inhibitory effect on the length and biomass of rice (Oryza sativa L.) used as a model plant. ZnO NP nanotoxicity caused rice root cell membrane damage, increased the malondialdehyde content, and activated antioxidant enzymes. As a control, the same dose of Zn2+ salt did not affect the physiological and biochemical indices of rice, suggesting that the toxicity is caused by the entry of the ZnO NPs and not the dissolved Zn2+. Laser ablation inductively coupled plasma optical emission spectroscopy analysis revealed that ZnO NPs accumulated in the rice root vascular tissues of the rhizodermis and procambium. Furthermore, transmission electron microscopy confirmed that the NPs were internalized to the root tissues. These results suggest that ZnO NPs may exist in the rice root system and that their particle size could be a crucial factor in determining toxicity. This study provides evidence of the size-dependent phytotoxicity of ZnO NPs.

Mass Spectrometry Imaging Strategy for In Situ Quantification of Soot in Size-Segregated Air Samples.

Soot, mainly derived from incomplete combustion of fossil fuel and biomass, exists ubiquitously in different environmental matrixes. To study the detrimental effects of soot on climate, air quality, and human health, accurate quantification of soot is an important prerequisite. However, until now, quantification of soot in environmental media, especially in carbonaceous media, is still very challenging. Here, we report a matrix-free laser desorption/ionization mass spectrometry (LDI-MS) method for in situ imaging of soot particles in size-segregated aerosol samples collected on filter membranes. A series of round-shaped sample spots in filter membranes were selected and subjected to MS imaging analysis, enabling direct in situ quantification of soot without solvent extraction or separation. Especially, the MS imaging with serial sample spots can overcome the problems of sweet-spot in LDI-MS and inhomogeneous distribution of soot in the filter membrane, thus greatly improving the precision of quantification. The limit of detection of soot was 4 ng/m2 and the recovery was 84.4-126%. By using this method, we found that a higher soot content was present in larger-sized particulate matter than smaller-sized particles, suggesting that aerosol soot was mainly derived from primary emission sources. Furthermore, this method also shows the potential to analyze nitrate and sulfate species in PM2.5. To the best of our knowledge, it is the first method capable of simultaneous analysis of inorganic salts and soot in air samples. It represents a novel strategy for in situ quantification of aerosol soot with the advantages of high specificity, high sensitivity, separation-, solvent- and matrix-free.

Semiquantitative Screening of THC Analogues by Silica Gel TLC with an Ag(I) Retention Zone and Chromogenic Smartphone Detection.

With the ever-evolving cannabis industry, low-cost and high-throughput analytical methods for cannabinoids are urgently needed. Normally, (potentially) psychoactive cannabinoids, typically represented by Δ9-tetrahydrocannabinol (Δ9-THC), and nonpsychoactive cannabinoids with therapeutic benefits, typically represented by cannabidiol (CBD), are the target analytes. Structurally, the former (tetrahydrocannabinolic acid (THCA), cannabinol (CBN), and THC) have one olefinic double bond and the latter (cannabidiolic acid (CBDA), cannabigerol (CBG), and CBD) have two, which results in different affinities toward Ag(I) ions. Thus, a silica gel thin-layer chromatography (TLC) plate with the lower third impregnated with Ag(I) ions enabled within minutes a digital chromatographic separation of strongly retained CBD analogues and poorly retained THC analogues. The resolution (Rs) between the closest two spots from the two groups was 4.7, which is almost 8 times higher than the resolution on unmodified TLC. After applying Fast Blue BB as a chromogenic reagent, smartphone-based color analysis enabled semiquantification of the total percentage of THC analogues (with a limit of detection (LOD) of 11 ng for THC, 54 ng for CBN, and 50 ng for THCA when the loaded volume is 1.0 µL). The method was validated by analyzing mixed cannabis extracts and cannabis extracts. The results correlated with those of high-performance liquid chromatography with ultraviolet detection (HPLC-UV) (R2 = 0.97), but the TLC approach had the advantages of multi-minute analysis time, high throughput, low solvent consumption, portability, and ease of interpretation. In a desiccator, Ag(I)-TLC plates can be stored for at least 3 months. Therefore, this method would allow rapid distinction between high and low THC varieties of cannabis, with the potential for on-site applicability.

pH as a Key Factor for the Quality Assurance of the Preparation of Gastrodiae Rhizoma Formula Granules.

Gastrodiae rhizoma (GR) formula granules and preparations have been used as a popular traditional Chinese medicine for clinical treatment since they have good pharmacological activity to treat nervous system diseases. Gastrodin and parishins have been the main active components in aqueous extracts for GR formula granules, but their pharmacological activities and metabolism are different. For quality control of the extracts, the extraction conditions should be investigated to accurately control the contents of two kinds of components. In this paper, the transfer rate of six index components (including gastrodin, p-hydroxybenzyl alcohol, parishin A, parishin B, parishin C, and parishin E) obtained by HPLC were used as indicators to investigate the effect of pH on the GR extraction process. The results demonstrated that pH is a key factor for preventing transforming parishins into gastrodin and maintaining high content of parishins in the extracts. It can be concluded that the weak acid environment could improve the transfer rate of parishins, thus ensuring the gastrodin and parishins consistency between GR raw materials and its aqueous extracts. Therefore, pH is an essential condition for accurate quality control of the extracts.

Comparison of HBV reactivation between patients with high HBV-DNA and low HBV-DNA loads undergoing PD-1 inhibitor and concurrent antiviral prophylaxis.

BACKGROUND: Programmed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor in patients with high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and PD-1 inhibitor. METHODS: This was a retrospective study including consecutive hepatitis B surface antigen-positive HCC patients who received PD-1 inhibitor and concurrent antiviral prophylaxis for prevention of clinical hepatitis. Patients were divided into low HBV-DNA group (low group, ≤ 500 IU/ml) and high HBV-DNA group (high group, > 500 IU/ml) according to the baseline HBV-DNA level. The incidences of HBV reactivation, HBV-associated hepatitis, and PD-1 inhibitor disruption were compared between the two groups. RESULTS: Two hundred two eligible patients were included: 94 in the low group and 108 in the high group. Seven patients (5 in the low group and 2 in the high group) developed HBV reactivation, and all recovered from HBV reactivation and HBV-associated hepatitis. The incidence of HBV reactivation in the two groups was low (5.3% vs 1.9%, P = 0.34). There was also no difference in the incidence of HBV-associated hepatitis (P = 0.56), or PD-1 inhibitor disruption (P = 0.82). The multivariable analysis showed PD-1 inhibitor with hepatic arterial infusion chemotherapy was the only significant risk factor for HBV reactivation (P = 0.04) and hepatitis (P = 0.002). CONCLUSION: With concurrent antiviral prophylaxis, HBV-DNA load higher than 500 IU/ml should not be a contraindication for PD-1 inhibitor.

Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro.

BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. METHODS: The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. RESULTS: IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC. CONCLUSIONS: This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy.

Rapid microwave-assisted Porter method for determination of proanthocyanidins.

INTRODUCTION: Proanthocyanidins have been widely developed and utilised in food, medicine, health care products and cosmetics. Porter-high-performance liquid chromatography (HPLC) is a quantitative method often utilised in many fields. This method uses a water bath to reflux the proanthocyanidins, but the process is cumbersome, the reagent consumption is large, and multiple batches of simultaneous treatments cannot be evaluated. OBJECTIVE: To establish a more convenient, rapid and high-batch processing method for determining the content of proanthocyanidins in functional food by HPLC. METHODS: N-Butanol-hydrochloric acid and iron salt are used as the reaction medium in the Porter method. After investigating the optimal conditions, the hydrolysis of proanthocyanidins can be performed in a microwave reactor at a power of 640 W for 75 s in the Porter reaction system. The content of proanthocyanidins was determined by HPLC with external standards. RESULTS: After the rapid pretreatment of samples, proanthocyanidins were determined by HPLC with a diode array detector at a detection wavelength of 525 nm with 0.53 µg/mL and 1.61 µg/mL limits of detection and quantification, respectively, for proanthocyanidin ions, and the linearity was 0.9999. Intra- and inter-day relative standard deviation values were between 1.5% and 3.1%, and the recovery was between 91.40% and 107.43% for the determination of different products, such as capsules, tablets and tea, which were similar to the values obtained with the conventional Porter method. CONCLUSION: This method is a time-saving and low cost approach for quantitative analysis of various proanthocyanidin health products that offers the advantages of high-batch processing and environmental friendliness.

NAP1L1 is a prognostic biomarker and contribute to doxorubicin chemotherapy resistance in human hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most fatal cancers, and its molecular basis needs to be delineated to identify biomarkers for its potential treatment. The purpose of this study was to identify a novel gene, nucleosome assembly proteins 1-like 1 protein (NAP1L1), associated with aggressive phenotypes of HCC. METHODS: Immunohistochemical staining was used to detect NAP1L1 protein expression in HCC tissues. The prognostic value of NAP1L1 expression was determined using Kaplan-Meier analysis and the Cox proportional hazards model. CCK-8 and apoptosis assays were used to detect the chemosensitivity in vitro. Xenograft tumor models were used to evaluate tumor cell proliferation and chemosensitivity in vivo. RESULTS: NAP1L1 expression was significantly upregulated in tumor tissues as compared to adjacent non-tumor tissues. High NAP1L1 expression in HCC tissues was associated with aggressive clinicopathologic features, such as serum AFP levels, tumor size and tumor number. Patients with high NAP1L1 expression had poor overall survival in our cohort and in the extra-validation cohort analyzed by TCGA microarray dataset and was further identified as an independent prognostic factor in HCC patients treated with radical resection. Both in vitro and in vivo assays showed that NAP1L1 promoted HCC cell proliferation and contribute to chemotherapy resistance. Further analyses found that some certain stemness associated genes were decreased concurrently with NAP1L1 down-regulation in HCC cell lines. CONCLUSIONS: Our findings support that NAP1L1 is a prognostic biomarker and may contribute to chemotherapy resistance in human hepatocellular carcinoma.

Comparison of Stable and Unstable Ethiodized Oil Emulsions for Transarterial Chemoembolization of Hepatocellular Carcinoma: Results of a Single-Center Double-Blind Prospective Randomized Controlled Trial.

PURPOSE: To compare the stability of stable and unstable water-in-oil emulsions and the efficacy and safety of these emulsions in a single-center, prospective double-blind trial of transarterial chemoembolization for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 812 patients with inoperable HCC were randomized (stable emulsion, n = 402; unstable emulsion, n = 410). The 2 emulsions were prepared by using the same protocol except that different solvents were used for chemotherapy agents, including epirubicin, lobaplatin, and mitomycin C. The solvent in the stable emulsion arm was contrast medium and distilled water, and the solvent in the unstable emulsion arm was distilled water. The primary endpoint was overall survival (OS), and secondary endpoints were time to progression (TTP), tumor response, adverse events (AEs), and plasma epirubicin concentrations. RESULTS: In vitro, stable emulsions did not occur until 1 day, and unstable emulsions, with a lower peak plasma concentration (P = .001) in vivo, exhibited rapid separation of the oil and aqueous phases after 10 minutes. Median OS times in the stable and unstable emulsion arms were 17.7 and 19.2 months, respectively (P = .81). No differences were found in TTP, tumor response, and AEs except for myelosuppression (anemia, 3.5% vs 7.6%; thrombocytopenia, 11.5% vs 17.7%), which was significantly more severe and frequent in the unstable emulsion arm (P = .013). CONCLUSIONS: Chemoembolization is equally effective with the use of stable and unstable emulsions, but the use of a stable emulsion has the advantage of less myelosuppression and a favorable pharmacokinetic profile.

Spectroscopic and molecular docking study on the structure-affinity relationship and mechanism in the interaction of genistein and its derivatives with bovine serum albumin.

In this paper, the interaction of genistein (GEN) and its four derivatives (GEN1-4) with bovine serum albumin (BSA) were investigated by ultraviolet-visible absorption spectra, fluorescence, synchronous fluorescence, three-dimensional fluorescence spectroscopy, circular dichroism and molecular docking techniques. The experimental results showed that the intrinsic fluorescence of BSA was quenched by genisteins and was due to the formation of a genisteins-BSA complex. The quenching constant, binding constants, binding sites, intermolecular distances and thermodynamic properties were calculated at 298 K, 306 K and 310 K. Site marker competitive experiments indicated that the binding site of genisteins to BSA was mainly located in subdomain IIA. The conformational investigation showed that the presence of 0020 genisteins led to changes in the secondary structure of BSA and induced the slight unfolding of protein polypeptides, which confirmed some micro-environmental and conformational changes of BSA molecules. Furthermore, the binding affinity decreased in the order GEN1 > GEN > GEN4 > GEN3 > GEN2, which revealed that different type and position of substituents of genistein significantly influenced the affinity of compounds to BSA. The number of hydroxyl groups on the ring A was the most important factor because increasing the hydroxyl groups on ring A clearly enhanced the binding affinity. However, trifluoromethylation did not much affect the affinity, alkylation, esterification and difluoromethylation slightly enhanced the binding affinity. The results obtained herein will provide valuable information about the pharmacokinetics at a molecular level and be a useful guideline for the further design of much more suitable genistein derivatives.

The perivascular phenotype and behaviors of dedifferentiated cells derived from human mature adipocytes.

Derived from mature adipocytes, dedifferentiated fat (DFAT) cells represent a special group of multipotent cells. However, their phenotype and cellular nature remain unclear. Our study found that human DFAT cells adopted perivascular characteristics and behaviors. Flow cytometry and immunofluorescent staining revealed that human DFAT cells positively expressed markers highly related to perivascular cell lineages, such as CD140b, NG2 and desmin, but were negative for common endothelial markers, including CD31, CD34, and CD309. Furthermore, DFAT cells displayed vascular network formation ability in Matrigel, and they noticeably promoted and stabilized the vessel structures formed by human umbilical vascular endothelial cells (HUVECs) in vitro. These results provide novel evidence on the pericyte nature of human DFAT cells, further supporting the recent model for the perivascular origin of adult stem cells, in which tissue-specific progenitor cells in mesenchymal tissues associate with blood vessels, exhibiting perivascular characteristics and functions.

New perspectives on dietary-derived treatments and food safety-antinomy in a new era.

Despite the advances in science and technology and wide use of chemical drugs, dietary intervention (or food therapy) remains useful in preventing or treating many human diseases. A huge body of evidence shows that the dietary pattern or habit is also an important contributing factor to the development of chronic diseases such as hypertension, type 2 diabetes, hyperlipidemia, and cancers. In recent years, over-the-counter health foods, nutraceuticals, and plant-derived medicinal products have been gaining popularity all over the world, particularly in developed countries. Unfortunately, owing to the contamination with various harmful substances in foods and the presence of toxic food components, food-borne diseases have also become increasingly problematic. Incidents of food poisonings or tainted food have been increasing worldwide, particularly in China and other developing countries. Therefore, the government should put in a greater effort in enforcing food safety by improving the surveillance mechanism and exerting highest standards of quality control for foods.

Effects of moderate static magnetic fields on the voltage-gated sodium and calcium channel currents in trigeminal ganglion neurons.

AIM: To study the effects of static magnetic fields (SMF) on the electrophysiological properties of voltage-gated sodium and calcium channels on trigeminal ganglion (TRG) neurons. METHODS: Acutely dissociated TRG neurons of neonatal SD rats were exposed to 125-mT and 12.5-mT SMF in exposure devices and whole-cell patch-clamp recordings were carried out to observe the changes of voltage-gated sodium channels (VGSC) and calcium channels (VGCC) currents, while laser scanning confocal microscopy was used to detect intracellular free Ca(2+) concentration in TRG neurons, respectively. RESULTS: (1) No obvious change of current-voltage (I-V) relationship and the peak current densities of VGSC and VGCC currents were found when TRG neurons were exposed to 125-mT and 12.5-mT SMF. However, the activation threshold, inactivation threshold and velocity of the channel currents above were significantly altered by 125-mT and 12.5-mT SMF. (2) The fluctuation of intracellular free Ca(2+) concentration within TRG neurons were slowed by 125-mT and 12.5-mT SMF. When SMF was removed, the Ca(2+) concentration level showed partial recovery in the TRG neurons previously exposed by 125-mT SMF, while there was a full recovery found in 12.5-mT-SMF-exposed neurons. CONCLUSIONS: Moderate-intensity SMF could affect the electrophysiological characteristics of VGCS and VGCC by altering their activation and inactivation threshold and velocity. The fluctuations of intracellular free Ca(2+) caused by SMF exposure were not permanent in TRG neurons.

Down-regulation of miR-140 induces EMT and promotes invasion by targeting Slug in esophageal cancer.

BACKGROUND/AIMS: MicroRNAs (miRNAs) are reported to regulate cell invasion and functions by interfering with the translation of target mRNAs, but the role of miRNAs in esophageal cancer (EC) remains unclear. METHODS: RT-PCR and Western blot were used to detect the expression of miRNAs and candidate genes in EC samples (n=89). miR-140 mimics and inhibitor were tansfected in human TE-1 and Eca-109 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. The markers of EMT were detected by using Western blot. RESULTS: miR-140 expression was decreased in the EC tissues compared with the corresponding adjacent tumor tissues. Low expression of miR-140 promotes cell invasion by using transwell assay, while the effect of miR-140 high expression is reverse. Slug, a target gene of miR-140, was examined by luciferase assay and Western blot. CONCLUSIONS: miR-140 may regulate the cell invasion of EC via controlling Slug expression.

The phenotype and tissue-specific nature of multipotent cells derived from human mature adipocytes.

Dedifferentiated fat (DFAT) cells derived from mature adipocytes have been considered to be a homogeneous group of multipotent cells, which present to be an alternative source of adult stem cells for regenerative medicine. However, many aspects of the cellular nature about DFAT cells remained unclarified. This study aimed to elucidate the basic characteristics of DFAT cells underlying their functions and differentiation potentials. By modified ceiling culture technique, DFAT cells were converted from human mature adipocytes from the human buccal fat pads. Flow cytometry analysis revealed that those derived cells were a homogeneous population of CD13(+) CD29(+) CD105(+) CD44(+) CD31(-) CD34(-) CD309(-) α-SMA(-) cells. DFAT cells in this study demonstrated tissue-specific differentiation properties with strong adipogenic but much weaker osteogenic capacity. Neither did they express endothelial markers under angiogenic induction.

Developing porous honeycomb films using miktoarm star copolymers and exploring their application in particle separation.

This paper reports for the first time the synthesis and application of miktoarm star copolymers to produce highly ordered honeycomb films using the breath figure technique. Miktoarm star copolymer containing a cross-linked core and two arm species, e.g., polystyrene and poly(t-butyl acrylate), is successfully synthesized using ATRP in a one-pot arm-first method. Various experimental parameters, including polymer architectures, solvents, polymer concentrations, and substrates, are explored to investigate their effects on the structure of the honeycomb films. It is found that miktoarm star copolymers with high molecular weight and spherical shape could readily produce ordered honeycomb films in a broader range of concentrations and humidity than linear block copolymers with similar chemical compositions but lower molecular weight. Partial hydrolysis of poly(t-butyl acrylate) arm species in the honeycomb film transforms the surface property from hydrophobic to hydrophilic while maintaining the film's mechanical stability in water. This porous monolayer film with uniform pore size distribution and inter-connected pore channels is successfully applied for separation of microparticles with different sizes.

Probing the stability of metal-organic frameworks by structure-responsive mass spectrometry imaging.

The widespread application of metal-organic frameworks (MOFs) is seriously hindered by their structural instability and it is still very challenging to probe the stability of MOFs during application by current techniques. Here, we report a novel structure-responsive mass spectrometry (SRMS) imaging technique to probe the stability of MOFs. We discovered that intact CuBTC (as a model of MOFs) could generate the characteristic peaks of organic ligands and carbon cluster anions in laser desorption/ionization mass spectrometry, but these peaks were significantly changed when the structure of CuBTC was dissociated, thus enabling a label-free probing of the stability. Furthermore, SRMS can be performed in imaging mode to visualize the degradation kinetics and reveal the spatial heterogeneity of the stability of CuBTC. This technique was successfully applied in different application scenarios (in water, moist air, and CO2) and also validated with different MOFs. It thus provides a versatile new tool for better design and application of environment-sensitive materials.

Dynamic Single-Cell RNA-Seq reveals mechanism of Selinexor-Resistance in Chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a type of hematologic malignancies caused by BCR-ABL chimeric oncogene. Resistance to tyrosine kinase inhibitors (TKIs) leads to the progression of CML into advanced stages. Selinexor is a small molecule inhibitor that targets a nuclear transporter called Exportin 1. Combined with imatinib, selinexor has been shown to disrupt nuclear-cytoplasmic transport signal of leukemia stem cells, resulting in cell death. The objective of this study was to investigate the mechanism of drug resistance to selinexor in CML. We established K562 cell line resistant to selinexor and conducted single cell dynamic transcriptome sequencing to analyze the heterogeneity within the parental and selinexor resistant cell populations. We identified specific gene expression changes associated with resistance to selinexor. Our results revealed differential expression patterns in genes such as MT2A, TFPI, MTND3, and HMGCS1 in the total RNA, as well as MT-TW, DNAJB1, and HSPB1 in the newly synthesized RNA, between the parental and drug-resistant groups. By applying pseudo-time analysis, we discovered that a specific cluster of cells exhibited characteristics of tumor stem cells. Furthermore, we observed a gradual decrease in the expression of ferroptosis-related molecules as drug resistance developed. In vitro experiments confirmed that the combination of a ferroptosis inducer called RSL3 effectively overcame drug resistance. In conclusion, this study revealed the resistance mechanism of selinexor in CML. In conclusion, we identified a subgroup of CML cells with tumor stem cell properties and demonstrated that ferroptosis inducer improved the efficacy of selinexor in overcoming drug resistance.