Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion.

Immune exclusion predicts poor patient outcomes in multiple malignancies, including triple-negative breast cancer (TNBC)1. The extracellular matrix (ECM) contributes to immune exclusion2. However, strategies to reduce ECM abundance are largely ineffective or generate undesired outcomes3,4. Here we show that discoidin domain receptor 1 (DDR1), a collagen receptor with tyrosine kinase activity5, instigates immune exclusion by promoting collagen fibre alignment. Ablation of Ddr1 in tumours promotes the intratumoral penetration of T cells and obliterates tumour growth in mouse models of TNBC. Supporting this finding, in human TNBC the expression of DDR1 negatively correlates with the intratumoral abundance of anti-tumour T cells. The DDR1 extracellular domain (DDR1-ECD), but not its intracellular kinase domain, is required for immune exclusion. Membrane-untethered DDR1-ECD is sufficient to rescue the growth of Ddr1-knockout tumours in immunocompetent hosts. Mechanistically, the binding of DDR1-ECD to collagen enforces aligned collagen fibres and obstructs immune infiltration. ECD-neutralizing antibodies disrupt collagen fibre alignment, mitigate immune exclusion and inhibit tumour growth in immunocompetent hosts. Together, our findings identify a mechanism for immune exclusion and suggest an immunotherapeutic target for increasing immune accessibility through reconfiguration of the tumour ECM.

Cytochrome P450 2B6 and UDP-Glucuronosyltransferase Enzyme-Mediated Clearance of Ciprofol (HSK3486) in Humans: The Role of Hepatic and Extrahepatic Metabolism.

Ciprofol (HSK3486) is a novel intravenous agent for general anesthesia. In humans, HSK3486 mainly undergoes glucuronidation to form M4 [fraction of clearance (fCL): 62.6%], followed by the formation of monohydroxylated metabolites that further undergo glucuronidation and sulfation to produce M5-1, M5-2, M5-3, and M3 (summed fCL: 35.2%). However, the complete metabolic pathways of HSK3486 in humans remain unclear. In this study, by comparison with chemically synthesized reference standards, three monohydroxylated metabolites [M7-1, 4-hydroxylation with an unbound intrinsic clearance (CLint,u) of 2211 µl/min/mg; M7-2, ω-hydroxylation with a CLint,u of 600 µl/min/mg; and M7-3, (ω-1)-hydroxylation with a CLint,u of 78.4 µl/min/mg] were identified in human liver microsomes, and CYP2B6 primarily catalyzed their formation. In humans, M7-1 was shown to undergo glucuronidation at the 4-position and 1-position by multiple UDP-glucuronosyltransferases (UGTs) to produce M5-1 and M5-3, respectively, or was metabolized to M3 by cytosolic sulfotransferases. M7-2 was glucuronidated at the ω position by UGT1A9, 2B4, and 2B7 to form M5-2. UGT1A9 predominantly catalyzed the glucuronidation of HSK3486 (M4). The CLint,u values for M4 formation in human liver and kidney microsomes were 1028 and 3407 µl/min/mg, respectively. In vitro to in vivo extrapolation analysis suggested that renal glucuronidation contributed approximately 31.4% of the combined clearance. In addition to HSK3486 glucuronidation (M4), 4-hydroxylation (M7-1) was identified as another crucial oxidative metabolic pathway (fCL: 34.5%). Further attention should be paid to the impact of CYP2B6- and UGT1A9-mediated drug interactions and gene polymorphisms on the exposure and efficacy of HSK3486. SIGNIFICANCE STATEMENT: This research elucidates the major oxidative metabolic pathways of HSK3486 (the formation of three monohydroxylated metabolites: M7-1, M7-2, M7-3) as well as definitive structures and formation pathways of these monohydroxylated metabolites and their glucuronides or sulfate in humans. This research also identifies major metabolizing enzymes responsible for the glucuronidation (UGT1A9) and oxidation (CYP2B6) of HSK3486 and characterizes the mechanism of extrahepatic metabolism. The above information is helpful in guiding the safe use of HSK3486 in the clinic.

Cas13d knockdown of lung protease Ctsl prevents and treats SARS-CoV-2 infection.

SARS-CoV-2 entry into cells requires specific host proteases; however, no successful in vivo applications of host protease inhibitors have yet been reported for treatment of SARS-CoV-2 pathogenesis. Here we describe a chemically engineered nanosystem encapsulating CRISPR-Cas13d, developed to specifically target lung protease cathepsin L (Ctsl) messenger RNA to block SARS-CoV-2 infection in mice. We show that this nanosystem decreases lung Ctsl expression in normal mice efficiently, specifically and safely. We further show that this approach extends survival of mice lethally infected with SARS-CoV-2, correlating with decreased lung virus burden, reduced expression of proinflammatory cytokines/chemokines and diminished severity of pulmonary interstitial inflammation. Postinfection treatment by this nanosystem dramatically lowers the lung virus burden and alleviates virus-induced pathological changes. Our results indicate that targeting lung protease mRNA by Cas13d nanosystem represents a unique strategy for controlling SARS-CoV-2 infection and demonstrate that CRISPR can be used as a potential treatment for SARS-CoV-2 infection.

Cooperative Characterization of In Situ TEM and Cantilever-TGA to Optimize Calcination Conditions of MnO2 Nanowire Precursors.

Calcination plays a vital role during material preparation. However, the calcination conditions have often been determined empirically or have been based on trial and error. Herein we present a cooperative characterization approach to optimize calcination conditions by gas-cell in situ TEM in collaboration with microcantilever-based thermogravimetric analysis (cantilever-TGA) techniques. The morphological evolution of precursors under atmospheric conditions is observed with in situ TEM, and the right calcination temperature is provided by cantilever-TGA. The proposed approach successfully optimizes the calcination conditions of fragile MnO2 nanowire precursors with multiple valence products. The cantilever-TGA shows that a calcination temperature above 560 °C is required to transform the MnO2 precursor to Mn3O4 under an N2 atmosphere, but the in situ TEM indicates that the nanowire structure is destroyed within only 30 min under calcination conditions. Our method further suggests that heating the precursor at 400 °C using an H2-containing atmosphere can produce Mn3O4 nanowires with good electrical properties.

The immune imbalance between follicular regulatory and helper T cells in myelin oligodendrocyte glycoprotein IgG-associated disease.

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a newly defined inflammatory demyelinating disease of the central nervous system. Currently, no immuno-modulatory treatment has been approved for MOGAD. We explored the function of follicular regularoty T (Tfr) and follicular helper T (Tfh) cells in patients with MOGAD. The number of circulating Tfr and Tfh cells and their expression of functional markers were accessed by flow cytometry. Circulating Tfr, Tfh, and B cells were further sorted and co-cultured in vitro to examine the influence of Tfr on Tfh-mediated B cell differentiation. In patients with MOGAD, the percentage of circulating PD-1hi Tfh cells elevated while the frequency of circulating activated Tfr cells decreased significantly. The Tfh/Tfr ratios positively correlated with the percentage of plasmblasts. In vitro, Tfh cells from patients with MOGAD exhibited a stronger capacity to promote the differentiation of plasmablasts through producing interleukin (IL)-21 than non-Tfh cells from patients, whereas Tfr cells suppressed this Tfh-mediated plasmablasts expansion, to a similar extent of IL-1 receptor antagonist (IL-1Ra). In conclusion, we revealed an immune imbalance of Tfr and Tfh cells in MOGAD. Tfr and IL-1Ra could be potential therapeutic targets in MOGAD.

Advanced In Situ TEM Microchip with Excellent Temperature Uniformity and High Spatial Resolution.

Transmission electron microscopy (TEM) is a highly effective method for scientific research, providing comprehensive analysis and characterization. However, traditional TEM is limited to observing static material structures at room temperature within a high-vacuum environment. To address this limitation, a microchip was developed for in situ TEM characterization, enabling the real-time study of material structure evolution and chemical process mechanisms. This microchip, based on microelectromechanical System (MEMS) technology, is capable of introducing multi-physics stimulation and can be used in conjunction with TEM to investigate the dynamic changes of matter in gas and high-temperature environments. The microchip design ensures a high-temperature uniformity in the sample observation area, and a system of tests was established to verify its performance. Results show that the temperature uniformity of 10 real-time observation windows with a total area of up to 1130 µm2 exceeded 95%, and the spatial resolution reached the lattice level, even in a flowing atmosphere of 1 bar.

MEMS Resonant Cantilevers for High-Performance Thermogravimetric Analysis of Chemical Decomposition.

We investigate the MEMS resonant cantilevers for high-performance thermogravimetric analysis (TGA) of chemical decomposition, featuring high accuracy and minimized thermal lag. Each resonant cantilever is integrated with a microheater for sample heating near the free end, which is thermally isolated from the resonance excitation and readout elements at the fixed end. Combining finite element modeling and experiments, we demonstrate that the sample loading region can stabilize within ~11.2 milliseconds in response to a step heating of 500 °C, suggesting a very fast thermal response of the MEMS resonant cantilevers of more than 104 °C/s. Benefiting from such a fast thermal response, we perform high-performance TG measurements on basic copper carbonate (Cu2(OH)2CO3) and calcium oxalate monohydrate (CaC2O4·H2O). The measured weight losses better agree with the theoretical values with 5-10 times smaller thermal lags at the same heating rate, compared with those measured by using conventional TGA. The MEMS resonant cantilevers hold promise for highly accurate and efficient TG characterization of materials in various fields.

DNA Deamination Is Required for Human APOBEC3A-Driven Hepatocellular Carcinoma In Vivo.

Although the APOBEC3 family of single-stranded DNA cytosine deaminases is well-known for its antiviral factors, these enzymes are rapidly gaining attention as prominent sources of mutation in cancer. APOBEC3's signature single-base substitutions, C-to-T and C-to-G in TCA and TCT motifs, are evident in over 70% of human malignancies and dominate the mutational landscape of numerous individual tumors. Recent murine studies have established cause-and-effect relationships, with both human APOBEC3A and APOBEC3B proving capable of promoting tumor formation in vivo. Here, we investigate the molecular mechanism of APOBEC3A-driven tumor development using the murine Fah liver complementation and regeneration system. First, we show that APOBEC3A alone is capable of driving tumor development (without Tp53 knockdown as utilized in prior studies). Second, we show that the catalytic glutamic acid residue of APOBEC3A (E72) is required for tumor formation. Third, we show that an APOBEC3A separation-of-function mutant with compromised DNA deamination activity and wildtype RNA-editing activity is defective in promoting tumor formation. Collectively, these results demonstrate that APOBEC3A is a "master driver" that fuels tumor formation through a DNA deamination-dependent mechanism.

Probucol attenuates high glucose-induced Müller cell damage through enhancing the Nrf2/p62 signaling pathway.

PURPOSE: This study investigated the protective effect of probucol on Müller cells exposed to high glucose conditions and examined potential mechanisms of action. METHODS: Primary human retinal Müller cells were incubated with high glucose (HG, 35 mM) in the present or absence of different concentrations of probucol for 24 h. Cell viability was determined using the CCK-8 method. Mitochondrial membrane potential (MMP) was measured using JC-1 staining and cell cycle by flow cytometry. The expression of nuclear factor E2-related factor 2 (Nrf2), glutamate-cysteine ligase catalytic subunit, and p62 was quantified using quantitative polymerase chain reaction and western blot. RESULTS: We found that HG inhibited cell proliferation, arrested cell cycle, and increased MMP in human Müller cells. Probucol activated the Nrf2/p62 pathway and upregulated the anti-apoptotic protein, Bcl2, and attenuated HG-mediated damage in Müller cells. CONCLUSIONS: Our results suggest that probucol may protect Müller cells from HG-induced damage through enhancing the Nrf2/p62 signaling pathway.

In Situ Hydrogen Temperature-Programmed Reduction Technology Based on the Integrated Microcantilever for Metal Oxide Catalyst Analysis.

Hydrogen temperature-programmed reduction (H2-TPR) technique is significant for catalyst characterization. The available instruments typically measure the H2 consumption using a thermal conductivity detector (TCD), which is strongly affected by the produced H2O molecules. Herein, we demonstrate an in situ TPR technology based on a silicon microcantilever, in which resonance exciting/detecting components and heating electrodes for catalyst samples are integrated. The microcantilever-based H2-TPR technology requires only 20 ng of the sample and eliminates the requirements of TCD and cold trap. During the self-heating up to 1000 °C, reduction-induced mass change of the sample can be in situ measured with picogram-level resolution. Compared with the available instruments, the microcantilever-based H2-TPR technology directly and in situ measures the mass change of the sample, without using H2 consumption to indirectly represent the reduction process, thus significantly improving the characterization accuracy. The microcantilever-based TPR technology has been successfully used to characterize various metal oxide catalysts with satisfactory accuracy. The in situ TPR results of the three CuO samples with different grain sizes clearly distinguish their different maximum temperatures, revealing the size effect of the catalyst. The microcantilever can also be placed in a low-temperature test chamber, enabling successful frozen H2-TPR analysis of catalysts with low reduction temperatures, such as PdO. Featuring simplified operation but high detecting accuracy, the microcantilever-based in situ H2-TPR technology is promising in the analytic applications of advanced catalysts.

Short-term effect of low-dose rituximab on myasthenia gravis with muscle-specific tyrosine kinase antibody.

INTRODUCTION/AIMS: The study aims to investigate the short-term efficacy of low-dose rituximab and its effect on immunological biomarker levels in myasthenia gravis (MG) patients with antibodies against muscle-specific tyrosine kinase (MuSK-MG). METHODS: Twelve MuSK-MG patients were enrolled in this prospective, open-label, self-controlled pilot study. Clinical severity was evaluated at baseline and 6 mo after a single rituximab treatment (600 mg). B lymphocyte subtypes, MuSK antibody titers, together with levels of immunoglobulins, serum B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), soluble CD40L, and four exosomal microRNAs were evaluated. A correlation matrix to reveal pairwise relationships among above variables was also generated. RESULTS: The single rituximab treatment significantly lowered the clinical severity scores and reduced daily dosage of prednisone (P = .032) at 6 mo. MuSK antibody titers decreased (P = .035) without significant changes in immunoglobulin levels. Serum BAFF level increased (P = .010), which negatively correlated with the percentages of B cells in lymphocytes as well as clinical severity. Additionally, serum exosomal miR-151a-3p showed a reduction of 28.1% (P = .031). DISCUSSION: We confirmed the clinical efficacy of low-dose rituximab in MuSK-MG, accompanied by a decrease in MuSK antibody titers and an increase in serum BAFF. Serum BAFF levels negatively correlated with B-cell counts as well as clinical severity.

Phenacyl Phenothiazinium Salt as a New Broad-Wavelength-Absorbing Photoinitiator for Cationic and Free Radical Polymerizations.

A novel broad-wavelength-absorbing photoinitiator based on phenacyl phenothiazinium hexafluroantimonate (P-PTh) possessing both phenacyl and phenothiazine chromophoric groups was reported. P-PTh absorbs light at UV, Visible and Near-IR region. Photophysical, photochemical, and computational investigations revealed that P-PTh in solution decomposes at all wavelengths by homolytic and heterolytic cleavages and generates cationic and radical species, which could efficiently initiate cationic and free radical polymerizations. It is anticipated that the photoinitiator with such wavelength flexibility may open up new pathways in curing applications of formulations of pigment systems.

Perineural invasion as a prognostic factor for intrahepatic cholangiocarcinoma after curative resection and a potential indication for postoperative chemotherapy: a retrospective cohort study.

BACKGROUND: In the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial. METHODS: ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated. RESULTS: There was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19-9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS and P = 0.8004 in OS). CONCLUSION: PNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.

Epigenomics-based identification of oestrogen-regulated long noncoding RNAs in ER+ breast cancer.

Breast cancer is one of the most prevalent cancers in women worldwide. Through the regulation of many coding and non-coding target genes, oestrogen (E2 or 17ß-oestradiol) and its nuclear receptor ERα play important roles in breast cancer development and progression. Despite the astounding advances in our understanding of oestrogen-regulated coding genes over the past decades, our knowledge on oestrogen-regulated non-coding targets has just begun to expand. Here we leverage epigenomic approaches to systematically analyse oestrogen-regulated long non-coding RNAs (lncRNAs). Similar to the coding targets of ERα, the transcription of oestrogen-regulated lncRNAs correlates with the activation status of ERα enhancers, measured by eRNA production, chromatin accessibility, and the occupancy of the enhancer regulatory components including P300, MED1, and ARID1B. Our 3D chromatin architecture analyses suggest that lncRNAs and their neighbouring E2-resonsive coding genes, exemplified by LINC00160 and RUNX1, might be regulated as a 3D structural unit resulted from enhancer-promoter interactions. Finally, we evaluated the expression levels of LINC00160 and RUNX1 in various types of breast cancer and found that their expression positively correlated with the survival rate in ER+ breast cancer patients, implying that the oestrogen-regulated LINC00160 and its neighbouring RUNX1 might represent potential biomarkers for ER+ breast cancers.

Investigating effects of preoperative inflammatory biomarkers on predicting survival outcomes of intrahepatic cholangiocarcinoma after curative resection.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) stands as the second most common malignant tumor in the liver with poor patient prognosis. Increasing evidences have shown that inflammation plays a significant role in tumor progression, angiogenesis, and metastasis. However, the prognosis significance of inflammatory biomarkers on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is poorly recognized. METHODS: ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were investigated. RESULTS: Receiver operating characteristic (ROC) curves showed no significance in NLR, PLR, and LMR in RFS and OS, while significant results were shown on SII in both RFS (P = 0.035) and OS (P = 0.034) with areas under ROC curve as 0.63 (95%CI 0.52-0.74) and 0.62 (95%CI 0.51-0.72), respectively. Kaplan-Meier curves revealed a statistically significant better survival data in SII-low groups on both RFS (P < 0.001) and OS (P < 0.001). The univariate and multivariate analyses revealed that higher level of SII was independently associated with both poorer RFS time and OS time. However, no significant result was shown on NLR, PLR, or LMR. CONCLUSION: SII is an effective prognostic factor for predicting the prognosis of ICC patient undergone curative hepatectomy, while NLR, PLR, and LMR are not associated with clinical outcomes of these patients.

Involvement of PpiD in Sec-dependent protein translocation.

The periplasmic space in between the inner and outer membrane of Gram-negative bacteria contains numerous chaperones that are involved in the biogenesis and rescue of extra-cytosolic proteins. In contrast to most of those periplasmic chaperones, PpiD is anchored by an N-terminal transmembrane domain within the inner membrane of Escherichia coli. There it is located in close proximity to the SecY subunit of the SecYEG translocon, which is the primary transporter for secretory and membrane proteins. By site-specific cross-linking we now found the periplasmic domain of PpiD also in close vicinity to the SecG subunit of the Sec translocon and we provide the first direct evidence for a functional cooperation between PpiD and the Sec translocon. Thus we demonstrate that PpiD stimulates in a concentration-dependent manner the translocation of two different secretory proteins into proteoliposomes that had been reconstituted with sub-saturating amounts of SecYEG. In addition we found ribosome-associated nascent chains of a secretory protein stalled at SecY also being in close contact to PpiD. Collectively these results suggest that PpiD plays a role in clearing the Sec translocon of newly translocated secretory proteins thereby improving the overall translocation efficiency. Consistent with this conclusion we demonstrate that PpiD contributes to the efficient detachment of newly secreted OmpA from the inner membrane and in doing so, seems to cooperate in a hierarchical manner with other periplasmic chaperones such as SurA, DegP, and Skp.

Three-dimensional analysis reveals altered chromatin interaction by enhancer inhibitors harbors TCF7L2-regulated cancer gene signature.

Distal regulatory elements influence the activity of gene promoters through chromatin looping. Chromosome conformation capture (3C) methods permit identification of chromatin contacts across different regions of the genome. However, due to limitations in the resolution of these methods, the detection of functional chromatin interactions remains a challenge. In the current study, we employ an integrated approach to define and characterize the functional chromatin contacts of human pancreatic cancer cells. We applied tethered chromatin capture to define classes of chromatin domains on a genome-wide scale. We identified three types of structural domains (topologically associated, boundary, and gap) and investigated the functional relationships of these domains with respect to chromatin state and gene expression. We uncovered six distinct sub-domains associated with epigenetic states. Interestingly, specific epigenetically active domains are sensitive to treatment with histone acetyltransferase (HAT) inhibitors and decrease in H3K27 acetylation levels. To examine whether the subdomains that change upon drug treatment are functionally linked to transcription factor regulation, we compared TCF7L2 chromatin binding and gene regulation to HAT inhibition. We identified a subset of coding RNA genes that together can stratify pancreatic cancer patients into distinct survival groups. Overall, this study describes a process to evaluate the functional features of chromosome architecture and reveals the impact of epigenetic inhibitors on chromosome architecture and identifies genes that may provide insight into disease outcome.

The effectiveness of TDF versus ETV on incidence of HCC in CHB patients: a meta analysis.

BACKGROUND: It has been proved that nucleos(t) ide analogues (NAs) therapy could improve underlying liver disease and reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the difference of effectiveness in reducing HCC occurrence between tenofovir (TDF) and enticavir (ETV), two first-line NAs drugs, is still little known. This meta analysis aims to assess the efficacy in reducing incidence of HCC comparing tenofovir monotherapy with entecavir monotherapy among chronic hepatitis B (CHB) patients by analyzing their long-term clinical outcomes. METHODS: Databases including PubMed, Embase, Cochrane Central Register of Controlled Trial, and ISI Web of Science were fully investigated according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. For the included articles, two of the authors independently extracted and confirmed relevant data. Review Manager software (RevMan 5.3) was using for meta analysis. RESULTS: Seven articles with 3698 patients were finally included in this research, 1574 in tenofovir group and 2124 in entecavir group. For meta analysis, the incidence of HCC was significantly lower among the tenofovir group than entecavir group [rate ratio (95% CI) of 0.66 (0.49, 0.89), P = 0.008], while there was no statistical significance in incidence of death or transplantation [rate ratio (95% CI) of 0.78 (0.55, 1.13), P = 0.19], encephalopathy [risk ratio (95% CI) of 0.72 (0.45, 1.13), P = 0.15] or variceal bleeding [risk ratio (95% CI) of 0.71 (0.34, 1.50), P = 0.37] between the two groups. CONCLUSION: There is a better effect of tenofovir in reducing HCC incidence than entecavir, which indicates tenofovir should be used more widely while treating chronic hepatitis B patients. However before applying, randomized controlled trial and large prospective cohort study should be performed in the future.

Molecular evidence of a toxic effect on a biofilm and its matrix.

Shewanella oneidensis MR-1 wild-type and a hyper-adhesive mutant CP2-1-S1 are used as model organisms and Cr(vi) is selected as a toxic chemical to study biofilm and toxic chemical interactions. Biofilms are cultured in a microfluidic device for in situ time-of-flight secondary ion mass spectrometry imaging. This approach is viable for studying biofilms' responses to antimicrobial resistance.

Investigation of Ion-Solvent Interactions in Nonaqueous Electrolytes Using in Situ Liquid SIMS.

Ion-solvent interactions in nonaqueous electrolytes are of fundamental interest and practical importance, yet debates regarding ion preferential solvation and coordination numbers persist. In this work, in situ liquid SIMS was used to examine ion-solvent interactions in three representative electrolytes, i.e., lithium hexafluorophosphate (LiPF6) at 1.0 M in ethylene carbonate (EC)-dimethyl carbonate (DMC) and lithium bis(fluorosulfonyl)imide (LiFSI) at both low (1.0 M) and high (4.0 M) concentrations in 1,2-dimethoxyethane (DME). In the positive ion mode, solid molecular evidence strongly supports the preferential solvation of Li+ by EC. Besides, from the negative spectra, we also found that PF6- forms association with EC, which has been neglected by previous studies due to the relatively weak interaction. In both LiFSI in DME electrolytes, however, no evidence shows that FSI- is associated with DME. Furthermore, strong salt ion cluster signals were observed in the 1.0 M LiPF6 in EC-DMC electrolyte, suggesting that a significant amount of Li+ ions stay in the vicinity of anions. In sharp comparison, weak ion cluster signals were detected in dilute LiFSI in DME electrolyte, suggesting most ions are well separated, in agreement with our molecular dynamics simulation results. These findings indicate that with virtues of little bias on detecting positive and negative ions and the capability of directly analyzing concentrated electrolytes, in situ liquid SIMS is a powerful tool that can provide key evidence for improved understanding on the ion-solvent interactions in nonaqueous electrolytes. Therefore, we anticipate wide applications of in situ liquid SIMS on investigations of various ion-solvent interactions in the near future.