Response To Selection Research Articles

Targeting CD36-Mediated Lipid Metabolism by Selective Inhibitor-Augmented Antitumor Immune Responses in Oral Cancer.

The fatty acid receptor CD36 is expressed on various malignant cells and is suggested to contribute to tumor progression. CD36 is also expressed by several immune cells and involved in immune responses and may be a potential target in cancer immunotherapy. In this study, we investigated whether the selective inhibition of CD36 can inhibit tumor progression and facilitate an antitumor immune response in oral squamous carcinoma cells (OSCCs). We assessed the effects of sulfosuccinimidyl oleate sodium (SSO), a CD36 inhibitor, on the proliferation apoptosis and alteration in tumor cell surface expression levels of immune accessory molecules in vitro. We also assessed whether SSO-treated OSCCs could promote a T cell response via a Mixed Lymphocyte Reaction (MLR) assay. We also investigated the direct antitumor effects and immunomodulatory effects of SSO using a mouse oral cancer OSCC model. SSO treatment significantly inhibited OSCC proliferation, increased apoptotic cell death, and upregulated the cell surface expression of several immune accessory molecules, including CD83, MHC-Class II, and PD-L1. SSO-treated OSCCs augmented T cell proliferation following MLR. In vivo SSO administration significantly attenuated mouse tumor growth with an increased proportion of immune cells, including CD4+ T, CD8+ T, and dendritic cells; it also decreased the proportion of immune suppressive cells, such as myeloid-derived suppressor and regulatory T cells. These results suggest that the selective inhibition of CD36 can induce direct and indirect antitumor effects by facilitating host antitumor immune responses in OSCCs.

Thiol-chromene click reaction-triggered mitochondria-targeted ratiometric fluorescent probe for intracellular biothiol imaging.

Chromene as the efficient biothiol recognition site was widely used to develop fluorescent probes based on thiol-chromene click reaction. However, chromene-based fluorescent probes with the both properties of ratiometric measurement and mitochondria-targeted function have not been reported and remain challenging. In this paper, we skillfully designed and synthesized the first mitochondria-targeted ratiometric fluorescent probe (Probe 1) for biothiols based on chromene. Upon addition of biothiols (Cys, Hcy, and GSH), the absorption and fluorescence spectra of Probe 1 changed from 490 to 426nm and from 567 to 498nm respectively, accompanied by color changes from orange to pale yellow under natural light and from orange to blue under a 365-nm UV lamp, which can be attributed to the click reaction of biothiols with α,β-unsaturated ketone of chromene moiety, subsequent pyran ring-opening, and phenol formation as well as 1,6-elimination of p-hydroxybenzyl moiety. Probe 1 not only exhibited high sensitivity (LODs of 149nM, 133nM, and 116nM for Cys, GSH, and Hcy respectively), rapid response, and excellent selectivity for biothiols (Cys, Hcy, and GSH), but also could target in mitochondria and ratiometrically image the fluctuation of intracellular biothiols. Moreover, the novel design strategy of modifying chromene to the N atom of pyridine was proposed for the first time.

Construction of a sequence activated fluorescence probe for simultaneous detection of γ-glutamyl transpeptidase and peroxynitrite in acute kidney injury

Acute kidney injury (AKI) can result in a sudden decline in kidney function and, if not promptly diagnosed and treated, can lead to a high mortality rate. Therefore, there is a critical need for the development of a non-invasive and dependable early diagnostic method for AKI to prevent its progression and deterioration. To address the risk of misdiagnosis or overlooked diagnosis due to reliance on a single biomarker, we developed a novel molecular fluorescent probe (HX-GP) to simultaneously detect and image two biomarkers, γ-Glutamyl transpeptidase (γ-GGT) and Peroxynitrite (ONOO−), in the AKI process. HX-GP can specifically detect γ-GGT in the red fluorescence channel (λem = 613 nm) and ONOO− in the green fluorescence channel (λem = 518 nm). HX-GP demonstrated high sensitivity, selectivity, and rapid response, showing excellent biocompatibility and detection performance. In addition, HX-GP was successful in imaging experiments in a cell model of cisplatin-induced AKI, a result that highlights its potential application value in early diagnosis of AKI.

Fabrication of chitosan-encapsulated microcapsules containing wood wax oil for antibacterial self-healing wood coatings

Wood multifunctional smart coating is a new functional coating that combines smart material technology with traditional wood. In this study, wood wax oil based on thistle oil and flaxseed oil was used as the core material, and chitosan was used as the wall material to prepare self-repairing antibacterial microcapsules. The optimal preparation conditions were found to be an oil-water ratio (OWR) of 2:1, a core-to-wall ratio of 3:1, using OP-10 as the emulsifier at a concentration of 10.0 %, and a crosslinker concentration of 0.18 g/mL. The encapsulation efficiency of microcapsules was 73.7 % by spray drying, and the thermal stability was improved. The chitosan microcapsules exhibit the characteristics of water sensitivity and acid selective response, with rapid release at pH 7.0. Blending microcapsules at concentrations of 2.0 %, 5.0 %, and 8.0 % with UV topcoat and applying them to walnut plywood resulted in a multifunctional wood coating. Artificially simulated daily scratch damage was effectively repaired within 7 d. Furthermore, the 10.0 % microcapsules demonstrated antibacterial properties against Escherichia coli (E. coli) and Escherichia coli (E. coli), with an antibacterial E. coli and S. aureus rate of up to 75.82 % and 42.96 %. The IC50 of the wood coatings against E. coli was 5.667, while against S. aureus it was 15.45. The minimum inhibitory concentration (MIC) of the microcapsules against both E. coli and S. aureus was 10.0 %. The coating film containing 2.0 % microcapsules demonstrated superior overall performance. This research established a foundation for the development of self-healing antibacterial coatings for wood and addressed the gap in dual-functional self-healing antibacterial paint films for wood.

H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition.

Radiotherapy (RT) is the primary treatment for diffuse midline glioma (DMG), a lethal pediatric malignancy defined by histone H3 lysine 27-to-methionine (H3K27M) mutation. Based on the loss of H3K27 trimethylation producing broad epigenomic alterations, we hypothesized that H3K27M causes a functional double-strand break (DSB) repair defect that could be leveraged therapeutically with PARP inhibitor and RT for selective radiosensitization and antitumor immune responses. H3K27M isogenic DMG cells and orthotopic brainstem DMG tumors in immune deficient and syngeneic, immune competent mice were used to evaluate the efficacy and mechanisms of PARP1/2 inhibition by olaparib or PARP1 inhibition by AZD9574 with concurrent RT. H3K27M mutation caused an HRR defect characterized by impaired RT-induced K63-linked polyubiquitination of histone H1 and inhibition of HRR protein recruitment. H3K27M DMG cells were selectively radiosensitized by olaparib in comparison to isogenic controls, and this effect translated to efficacy in H3K27M orthotopic brainstem tumors. Olaparib and RT induced an innate immune response and induction of NK cell (NKG2D) activating ligands leading to increased NK cell-mediated lysis of DMG tumor cells. In immunocompetent syngeneic orthotopic DMG tumors, either olaparib or AZD9574 in combination with RT enhanced intratumoral NK cell infiltration and activity in association with NK cell-mediated therapeutic responses and favorable activity of AZD9574. The HRR deficiency in H3K27M DMG can be therapeutically leveraged with PARP inhibitors to radiosensitize and induce an NK cell-mediated antitumor immune response selectively in H3K27M DMG, supporting the clinical investigation of best-in-class PARP inhibitors with RT in DMG patients. H3K27M DMG are HRR defective and selectively radiosensitized by PARP inhibitor.PARP inhibitor with RT enhances NKG2D ligand expression and NK cell-mediated lysis.NK cells are required for the therapeutic efficacy of PARP inhibitor and RT. Radiotherapy is the cornerstone of H3K27M-mutant diffuse midline glioma treatment, but almost all patients succumb to tumor recurrence with poor overall survival, underscoring the need for RT-based precision combination therapy. Here, we reveal HRR deficiency as an H3K27M-mediated vulnerability and identify a novel mechanism linking impaired RT-induced histone H1 polyubiquitination and the subsequent RNF168/BRCA1/RAD51 recruitment in H3K27M DMG. This model is supported by selective radiosensitization of H3K27M DMG by PARP inhibitor. Notably, the combination treatment results in NKG2D ligand expression that confers susceptibility to NK cell killing in H3K27M DMG. We also show that the novel brain penetrant, PARP1-selective inhibitor AZD9574 compares favorably to olaparib when combined with RT, prolonging survival in a syngeneic orthotopic model of H3K27M DMG. This study highlights the ability of PARP1 inhibition to radiosensitize and induce an NK cell-mediated antitumor immunity in H3K27M DMG and supports future clinical investigation.

Dopaminergic neurons lacking Caspase-3 avoid apoptosis but undergo necrosis after MPTP treatment inducing a Galectin-3-dependent selective microglial phagocytic response

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression.

Exploring Novel Approaches: Surface Functionalization of Metal Organic Semiconductor as Sensing Material for Volatile Organic Compounds Detection

Detecting volatile organic compounds (VOCs) is imperative in healthcare, industrial safety, and environmental monitoring due to their potential harm to human health and the environment. Addressing the challenges in VOC detection, research has focused on creating sensors with rapid response and high selectivity, notably through surface functionalization of metal organic semiconductors. Metal organic semiconductors offer advantages over standard metal oxide semiconductors (MOS), demonstrating superior sensitivity and selectivity even at low temperatures and concentrations. Notably, conductive particle-polymer hybrids and conjugated polymers as metal organic semiconductors show promise for VOCs detection. This review comprehensively explores surface functionalization in metal organic semiconductors, covering principles, mechanisms governing gas sensing behavior and the pivotal role of surface functionalization in enhancing selectivity and performance. Additionally, various surface functionalization options, such as nanoparticles, nanostructures, and organic ligands, are discussed.

The Genetic Architecture of Recombination Rates is Polygenic and Differs Between the Sexes in Wild House Sparrows (Passer domesticus).

Meiotic recombination through chromosomal crossing-over is a fundamental feature of sex and an important driver of genomic diversity. It ensures proper disjunction, allows increased selection responses, and prevents mutation accumulation; however, it is also mutagenic and can break up favorable haplotypes. This cost-benefit dynamic is likely to vary depending on mechanistic and evolutionary contexts, and indeed, recombination rates show huge variation in nature. Identifying the genetic architecture of this variation is key to understanding its causes and consequences. Here, we investigate individual recombination rate variation in wild house sparrows (Passer domesticus). We integrate genomic and pedigree data to identify autosomal crossover counts (ACCs) and intrachromosomal allelic shuffling (r¯intra) in 13,056 gametes transmitted from 2,653 individuals to their offspring. Females had 1.37 times higher ACC, and 1.55 times higher r¯intra than males. ACC and r¯intra were heritable in females and males (ACC h2 = 0.23 and 0.11; r¯intra h2 = 0.12 and 0.14), but cross-sex additive genetic correlations were low (rA = 0.29 and 0.32 for ACC and r¯intra). Conditional bivariate analyses showed that all measures remained heritable after accounting for genetic values in the opposite sex, indicating that sex-specific ACC and r¯intra can evolve somewhat independently. Genome-wide models showed that ACC and r¯intra are polygenic and driven by many small-effect loci, many of which are likely to act in trans as global recombination modifiers. Our findings show that recombination rates of females and males can have different evolutionary potential in wild birds, providing a compelling mechanism for the evolution of sexual dimorphism in recombination.

Coumarin-aurone based fluorescence probes for cysteine sensitive in-situ identification in living cells

The quantification of cysteine (Cys) levels in the organisms holds paramount significance in biological research and disease diagnosis, which can give the correlation between abnormal Cys levels and diseases. In this study, two fluorescent probes, designated as DEA-OH and DEA-AC, featuring a coumarin-aurone backbone specifically engineered for Cys detection, were meticulously designed and synthesized. The diethylamino coumarin-aurone probe DEA-OH and the acrylate-substituted probe DEA-AC demonstrated remarkable sensitivity in detecting cysteine by means of copper displacement (DEA-OH) and acrylate hydrolysis mechanisms (DEA-AC) with fluorescence detection limits of 7.25 μM and 1.65 μM, respectively. Moreover, the fluorescence peak wavelength of the two probes displayed a linear relationship with solvent polarity in the ET (30) range of 30–65 kcal•mol−1, indicating the potential for monitoring changes in environmental polarity within this ET (30) range. The outstanding attributes exhibited by DEA-AC including superior photostability, remarkable selectivity, and swift response (kinetic rate constant: 0.00747 s−1), coupled with the exceptional anti-interference ability, have significantly broadened its scope of applications, for example detecting alterations in Cys within biological systems.

Construction of a dual “off-on” near-infrared fluorescent probe for bioimaging of HClO in rheumatoid arthritis

Hypochlorous acid (HClO) serves as a critical biomarker in inflammatory diseases such as rheumatoid arthritis (RA), and its real-time imaging is essential for understanding its biological functions. In this study, we designed and synthesized a novel probe, RHMB, which ingeniously integrates rhodamine B and methylene blue fluorophores with HClO-specific responsive moieties into a single molecular framework. Upon exposure to HClO, RHMB exhibited significant dual-channel fluorescence enhancement characterized by high sensitivity (LODs of 2.55 nM and 14.08 nM), excellent selectivity, and rapid response time (within 5 s). Notably, RHMB enabled reliable imaging of both exogenous and endogenous HClO in living cells and in zebrafish, employing a unique duplex-imaging turn-on approach that highlighted its adaptability across various biological contexts. Furthermore, RHMB effectively monitored HClO fluctuations in an RA mouse model and assessed the therapeutic efficacy of diclofenac (Dic) in alleviating RA symptoms. These findings underscore the potential of RHMB as an invaluable tool for elucidating the biological roles of HClO in various diseases.

Thermal decomposition-assisted, aspect ratio controlled ZnO nanorods towards highly selective H2 gas detection

ZnO nanostructures with various aspect ratios have been synthesized for H2 gas detection applications. The thermal-decomposition method was employed at different annealing temperatures (350, 450, and 550 °C) and its impact on various shapes/sizes of ZnO nanostructures is demonstrated. Thermal decomposition performed at 350 °C exhibited a maximum (∼6.25) aspect ratio among them. Its capability of H2 sensing was also observed to be maximum by realizing ∼483% of sensor response at 180 °C under H2 gas concentration of 80 ppm. The sensor response is ∼3 times (∼177%) and ∼9 times (∼53%) higher at ZnO nanostructure synthesized at 350 °C than at 450 °C, and 550 °C, respectively. The higher sensor response has been attributed to the increased availability of active surface area for adsorption/desorption of gas molecules. ZnO@350 nanostructure showed significantly higher selectivity towards H2 gas than other target chemical inputs. We have also studied H2-induced metallization on the surface of ZnO nanostructures which plays an important role for improving the selectivity and sensor response. This study provides insight into the role of aspect-ratio-controlled shape/sized ZnO in improving H2 gas sensing.

Low-Volume Electrochemical Sensor Platform for Direct Detection of Paraquat in Drinking Water

Direct testing of pesticide contaminants in drinking water is a challenge. Portable and sensitive sensor platforms are desirable to test water contaminants directly at farm and consumer levels. In this study, we have demonstrated the feasibility of an electrochemical sensor for the direct detection of paraquat (PQ) in drinking water samples. An immunoassay-based sensing platform was fabricated using PQ-specific antibody immobilized on the surface of the electrochemically reduced graphene oxide (rGO) modified screen-printed carbon electrode (rGO-SPCE). Using non-faradaic electrochemical impedance spectroscopy (EIS) as a detection tool, the sensor platform demonstrated a dynamic response for PQ concentration in drinking water ranging from 0.05 ng/mL to 72.9 ng/mL (0.19 to 243.8 nM), with a coefficient of determination (r2) of 0.997 and a limit of detection of 0.05 ng/mL (0.19 nM). Percentage recovery within ±20% error was obtained, and the sensor cross-reactivity test showed a selective response against glyphosate antigen. With the flexibility to use single-frequency EIS and low sample volume, the developed sensor demonstrated testing in water samples directly without any sample pre-processing. This low-volume electroanalytical sensor platforms can be translated into portable testing tools for the detection of various water contaminants.

MOF-derived Mo-doped Co3O4: A hierarchical yeast-like structure for superior carbon monoxide sensing

Carbon monoxide (CO) is one of the most dangerous gases owing to its dual threat, role in global warming, and severe impact on human health. Metal-organic framework (MOF) gas-sensing materials have drawn the interest of many different sectors due to their unique structural characteristics. This study used a solvothermal technique and subsequent annealing to create a hierarchical, yeast-shaped Mo-Co3O4 material from a Co-MOF precursor. The prepared materials have been employed in the development of a CO-detection gas sensor. Gas-sensing experiments revealed that Mo-Co3O4 exhibited significantly improved sensing capabilities compared to pure Co3O4. Notably, at 200 °C, 2 mol% Mo-Co3O4 showed high response levels of about 136 at 100 ppm CO concentrations, approximately 50.4 times higher than pure Co3O4. Furthermore, the Mo-doped material exhibited a low detection threshold, excellent reproducibility, long-term stability, good selectivity, and rapid response and recovery times (78.5/55.3 s). Introducing Mo dopants into the Co3O4 material and the hierarchical yeast-like nanostructure are responsible for these improvements in gas-sensing capability.

Bioelectronic sensing platform emulating the human endocannabinoid system for assessing and modulating of cannabinoid activity

Cannabinoids are involved in physiological and neuromodulatory processes through their interactions with the human cannabinoid receptor-based endocannabinoid system. Their association with neurodegenerative diseases and brain reward pathways underscores the importance of evaluating and modulating cannabinoid activity for both understanding physiological mechanisms and developing therapeutic drugs. The use of agonists and antagonists could be strategic approaches for modulation. In this study, we introduce a bioelectronic sensor designed to monitor cannabinoid binding to receptors and assess their agonistic and antagonistic properties. We produced human cannabinoid receptor 1 (hCB1R) via an Escherichia coli expression system and incorporated it into nanodiscs (NDs). These hCB1R-NDs were then immobilized on a single-walled carbon nanotube field-effect transistor (swCNT-FET) to construct a bioelectronic sensing platform. This novel system can sensitively detect the cannabinoid ligand anandamide (AEA) at concentrations as low as 1 fM, demonstrating high selectivity and real-time response. It also successfully identified the hCB1R agonist Δ9-tetrahydrocannabinol and observed that the hCB1R antagonist rimonabant diminished the sensor signal upon AEA binding, indicating the antagonism-based modulation of ligand interaction. Consequently, our bioelectronic sensing platform holds potential for ligand detection and analysis of agonism and antagonism.

A versatile fluorescent probe for the ratiometric detection of hydrazine (N2H4) in water, soil, plant, and food samples

Hydrazine (N2H4) is a crucial chemical raw material extensively utilized in chemical production. However, due to its volatility, water solubility, and high toxicity, both the gaseous form and aqueous solution of N2H4 pose significant environmental risks by causing severe pollution that can adversely impact plants, microorganisms, and human health. Therefore, accurate detection of N2H4 in the environment is imperative for safeguarding public health. In this study, we synthesized a ratiometric fluorescent probe (BCaz-Cy2) based on Carbazole and Hemicyanine groups. This probe exhibits simple synthesis procedure, rapid response time, high sensitivity and selectivity as well as remarkable detection signals. It enables effective detection of N2H4 in various matrices such as water, food, soil and plant samples thereby significantly expanding the scope of applications for N2H4 probes.

Nanocomposite-modified nanopores: A promising platform for selective detection of copper ions

This research introduces an innovative platform designed for the selective detection of copper (II) (Cu2+) ions, employing a singular nanopore embedded within a 12 μ m-thick polyethylene terephthalate (PET) membrane. The track-etched nanopore was subsequently modified with nanomaterials in an allylamine hydrochloride (PAH)-modified asymmetric nanopore through electrostatic interactions. The nanomaterials included copper oxide (CuO), graphene oxide (GO), and their composite (GO/CuO), were synthesized using wet chemistry, and their structures and optical properties were thoroughly investigated using x-ray diffraction and diffuse reflectance spectroscopy. In the distinctive feature of the platform, Cu2+ ions gain access to coordination sites across a broad surface covered by the immobilized nanomaterials, facilitating effective binding. The selective response of GO/CuO modified pores towards Cu2+ ions was notably observed through ion transportation (I –V) studies, surpassing the response of unmodified nanopores and those modified with CuO alone. This selective behavior was demonstrated in the presence of various monovalent and divalent competing ions. Quantitative assessment of I –V studies was conducted by evaluating the intrinsic rectification ratio of asymmetric nanopores, providing a robust measure of platform's efficacy. Furthermore, we identified the optimal pH for detecting Cu2+ ions as 7, enhancing the specificity and accuracy of our method.

Synthesis of porous SnO2@Fe2O3 core-shell triple-shelled boxes with selective and rapid response towards HCHO

Heterogenous SnO2@Fe2O3 core-shell triple-layer boxes (TBs) are successfully prepared through using a combination of room-temperature hydrolyzation and annealing treatment on SnO2 double-layer boxes (DBs). The crystallinity, morphology, and microstructure of as-prepared SnO2@Fe2O3 TBs are detailedly characterized. Compared with those of referenced pristine SnO2 or Fe2O3 nanostructures, the overall cubic configuration of heterogeneous SnO2@Fe2O3 with hollow interiors retains largely unaltered. Meanwhile, sensor based on SnO2@Fe2O3 samples synthesized with Fe2O3/SnO2 mole ratio of 1 exhibit superior response, excellent selectivity, shortened response-recovery time, and good long-time stability for formaldehyde (HCHO). It has the highest response (11.72) with the response/recovery time of 4 s/19 s to 50 ppm HCHO, respectively, and a low detection limit (1.07 to 200 ppb) for targeted HCHO under the optimal operating temperature (220 °C). The high absorption ability based on unique structural merits of hierarchically SnO2/Fe2O3 subunit-assembled porous multilayers and synergistic effect of SnO2/Fe2O3 heterojunction may contribute to their excellent HCHO sensing performance.

A novel theranostic strategy for myocardial infarction through neutralization of endogenous SO2 using an endoplasmic reticulum-targeted fluorescent probe

Myocardial infarction (MI), one of the leading causes of death worldwide, urgently needs further understanding of the pathological process and effective therapies. SO2 in endoplasmic reticulum in several cardiovascular diseases has been reported to be particularly important. However, the role of endogenous SO2 in endoplasmic reticulum in treating myocardial infarction is still ambiguous and needs to be elucidated. Herein, we developed TPA-HI-SO2 as the first endoplasmic reticulum-targeting fluorescent agent for specific imaging and detection of sulfur dioxide derivatives both in vitro and in vivo. TPA-HI-SO2 shows a highly sensitive and selective response to SO2 derivatives over other anions in aqueous solution with a satisfactory response time and detection limit. Furthermore, TPA-HI-SO2 decreased the SO2 concentration in H9C2 cells treated with H2O2 and in an MI mouse model. Most importantly, TPA-HI-SO2 protects H9C2 cells from H2O2-induced apoptosis and obviously protects against myocardial infarction in vivo through neutralization of endogenous SO2. Taken together, we developed the first ER-targeting ratiometric fluorescent probe for endogenous SO2 with excellent biocompatibility, high selectivity and sensitivity in this paper. More importantly, we demonstrated an obvious increase of the endogenous SO2 concentration in a myocardial infarction mouse model for the first time, which suggests that neutralization of endogenous SO2 in endoplasmic reticulum could be a promising therapeutic strategy for myocardial infarction.

Response processes for patients providing quantitative self-report data: a qualitative study.

To identify factors that influence response processes for patients providing quantitative self-report data. Secondly, due to the lack of integrative and explanatory models in this area, to develop a model of patients' response processes that can guide what to look for when considering validity evidence and interpreting scores on individual items. Participants (n = 13) were recruited from a specialized substance use disorder treatment clinic and interviewed while responding to items from a clinical feedback system implemented for routine outcome monitoring in that setting. The interview approach was based on cognitive interviewing. Data collection and analysis were inspired by a grounded theory approach. We identified several variables that influenced the participants' response processes. The variables were organized into five categories: context-related variables; item-related variables; response base variables; reasoning strategies; and response selection strategies. We also found that the participants' responses for many items were affected by different aspects of the response process in ways that are relevant to interpretation but not necessarily discernible from the numerical scores alone, and we developed response categories to capture this. The findings suggest that patients providing quantitative self-report data encounter conditions in the response process that challenge and influence their ability to convey meaning and accuracy. This results in responses that for many of the items reflect messages important for interpretation and follow-up, even if it does not appear from the numerical scores alone. The proposed model may be a useful tool when developing items, assessing validity, and interpreting responses.

Multiplex Sensing of Biomarkers on the Cancer Cell Surface by an Epithelial-Mesenchymal Transition (EMT) Sensing Panel Enables Precise Differentiating of Cancer Cells at Various EMT Stages.

Epithelial-mesenchymal transition (EMT) is a complex process that plays a critical role in tumor progression. In this study, we present an EMT sensing panel for the classification of cancer cells at different EMT stages. This sensing panel consists of three types of fluorescent probes based on boronic acid-functionalized carbon-nitride nanosheet (BCN) derivatives. The selective response toward different EMT-associated biomarkers, namely, EpCAM, N-cadherin, and sialic acid (SA), was achieved by conjugating the corresponding antibodies to each BCN derivative, whereas the rare-earth-doping ensures simultaneous sensing of the three biomarkers with fluorescent emission of the three probes at different wavelengths. Sensitive sensing of the three biomarkers was achieved at the protein level with LODs reaching 1.35 ng mL-1 for EpCAM, 1.62 ng mL-1 for N-cadherin, and 1.54 ng mL-1 for SA. The selective response of these biomarkers on the cell surface also facilitated sensitive detection of MCF-7 cells and MDA-MB-231 cells with LODs of 2 cells/mL and 2 cells/mL, respectively. Based on the simultaneous sensing of the three biomarkers on cancer cells that underwent different extents of EMT, precise discrimination and classification of cells at various EMT stages were also achieved with an accuracy of 93.3%. This EMT sensing panel provided a versatile tool for monitoring the EMT evolution process and has the potential to be used for the evaluation of the EMT-targeting therapy and metastasis prediction.