A Wireless, CRISPR-Polymer Dot Electrochemical Sensor for the Diagnosis of Bacterial Pneumonia and Multi-Drug Resistance.

Rapid and accurate diagnosis is crucial for managing the global health threat posed by multidrug-resistant bacterial infections; however, current methods have limitations in either being time-consuming, labor-intensive, or requiring instruments with high costs. Addressing these challenges, we introduce a wireless electrochemical sensor integrating the CRISPR/Cas system with electroconductive polymer dot (PD) nanoparticles to rapidly detect bacterial pathogens from human sputum. To enhance the electroconductive properties, we synthesized copper-ion-immobilized PD (PD-Cu), followed by conjugation of the deactivated Cas9 protein (dCas9) onto PD-Cu-coated Si electrodes to generate the dCas9-PD-Cu sensor. The dCas9-PD-Cu sensor integrated with isothermal amplification can specifically detect target nucleic acids of multidrug-resistant bacteria, such as the antibiotic resistance genes kpc-2 and mecA. The dCas9-PD-Cu sensor exhibits high sensitivity, allowing for the detection of ∼54 femtograms of target nucleic acids, based on measuring the changes in resistivity of the Si electrodes through target capture by dCas9. Furthermore, a wireless sensing platform of the dCas9-PD-Cu sensor was established using a Bluetooth module and a microcontroller unit for detection using a smartphone. We demonstrate the feasibility of the platform in diagnosing multidrug-resistant bacterial pneumonia in patients' sputum samples, achieving 92% accuracy. The current study presents a versatile biosensor platform that can overcome the limitations of conventional diagnostics in the clinic.

The Impact of Head Elevation on Prevalence and Severity of Emergence Cough in Male Patients during Endotracheal Extubation.

BACKGROUND Emergence cough during endotracheal extubation can lead to complications. This cough is triggered by the deviation of the endotracheal tube from the airway anatomy, causing pressure on the airway mucosal wall. Head elevation has the potential to align the airway passage with the tube's configuration. In this study, we aimed to investigate the impact of head elevation using a pillow on the prevalence and severity of emergence cough in male patients. MATERIAL AND METHODS A total of 71 male patients undergoing laparoscopic cholecystectomy were randomly assigned to either the head elevation group (n=35) or the control group (n=36). The head elevation group maintained a position with a neck flexion angle of 35º using a pillow, while the control group remained in a neutral position after anesthetic induction. The severity of cough was assessed before, during, and after extubation using a 4-point scale, with grades 2 and 3 indicating cough and grade 3 indicating severe cough. RESULTS The characteristics and intraoperative data of the patients were similar between the two groups. There was no significant difference in the incidence of cough and severe cough between the groups. However, the severity of cough was significantly lower in the head elevation group compared to the control group before extubation (cough scale: 0/5/8/23 vs 1/2/17/15 in the control group vs the head elevation group, P=0.039). The time to extubation, respiratory complications, nausea, pain, and the number of patients receiving fentanyl were comparable between the groups. CONCLUSIONS Head elevation using a pillow effectively reduced the severity of cough before endotracheal extubation during anesthesia emergence in male patients. However, it did not significantly reduce the incidence of cough. These findings highlight the potential benefits of head elevation in minimizing the discomfort associated with emergence cough.

Upregulated FOXM1 stimulates chondrocyte senescence in Acot12-/-Nudt7-/- double knockout mice.

Rationale: One of the hallmarks of osteoarthritis (OA), the most common degenerative joint disease, is increased numbers of senescent chondrocytes. Targeting senescent chondrocytes or signaling mechanisms leading to senescence could be a promising new therapeutic approach for OA treatment. However, understanding the key targets and links between chondrocyte senescence and OA remains unclear. Methods: Senescent chondrocytes were identified from Nudt7-/-, Acot12-/-, double-knockout mice lacking Acot12 and Nudt7 (dKO) and applied to microarray. The presence of forkhead transcription factor M1 (FOXM1) was detected in aged, dKO, and destabilization of the medial meniscus (DMM) cartilages and articular chondrocytes, and the effect of FoxM1 overexpression and acetyl-CoA treatment on cartilage homeostasis was examined using immunohistochemistry, quantitative real-time PCR (qRT-PCR), cell apoptosis and proliferation assay, and safranin O staining. Delivery of Rho@PAA-MnO2 (MnO2 nanosheet) or heparin-ACBP/COS-GA-siFoxM1 (ACBP-siFoxM1) nanoparticles into DMM cartilage was performed. Results: Here, we propose the specific capture of acetyl-CoA with the delivery of (FoxM1 siRNA (siFoxM1) to prevent cartilage degradation by inhibiting the axis of chondrocyte senescence. dKO stimulate chondrocyte senescence via the upregulation of FoxM1 and contribute to severe cartilage breakdown. We found that the accumulation of acetyl-CoA in the dKO mice may be responsible for the upregulation of FoxM1 during OA pathogenesis. Moreover, scavenging reactive oxygen species (ROS) induced by chondrocyte senescence via the implantation of MnO2 nanosheets or delivery of siFoxM1 functionalized with acetyl-CoA binding protein (ACBP) to capture acetyl-CoA using an injectable bioactive nanoparticle (siFoxM1-ACBP-NP) significantly suppressed DMM-induced cartilage destruction. Conclusion: We found that the loss of Acot12 and Nudt7 stimulates chondrocyte senescence via the upregulation of FoxM1 and accumulation of acetyl-CoA, and the application of siFoxM1-ACBP-NP is a potential therapeutic strategy for OA treatment.

Multicolor Hair Dyeing with Biocompatible Dark Polyphenol Complex-Integrated Shampoo with Reactive Oxygen Species Scavenging Activity.

Hair dyeing has become a prevalent lifestyle trend, especially within the fashion industry. However, it possesses disadvantages, such as containing carcinogenic and toxic materials. In this study, we developed a biocompatible hair-dyeing technology using a shampoo with a dark polyphenol complex (DPC), referred to as S-DPC. The DPC was formed from a mixture of gallic acid and [1,1'-biphenyl]-2,2',4,4',5,5'-hexol and used to enhance both the stability of the hair coating and its ability to scavenge reactive oxygen species (ROS). Colloidal DPC particles play a pivotal role in the coating process of various hair dyes, ensuring the uniform coloring of human hair through intermolecular interactions such as hydrogen bonding. Owing to the effect of a polyphenol complex on hair coating, we observed improved antistatic performance and enhanced mechanical strength, resulting in a substantial increase in elongation at the breaking point from 33.74% to 48.85%. The multicolor S-DPC exhibited antioxidant properties, as indicated by its ROS-scavenging ability, including 2,2-diphenyl-1-picrylhydrazyl inhibition (87-89%), superoxide radical scavenging (84-87%), and hydroxyl radical scavenging (95-98%). Moreover, the in vitro analysis of the DPC revealed nearly 100% cell viability in live and dead assays, highlighting the remarkable biocompatibility of the DPC. Therefore, considering its effectiveness and safety, this biomaterial has considerable potential for applications in hair dyeing.

Stimuli-responsive pressure-strain sensor-based conductive hydrogel for alleviated non-alcoholic fatty liver disease by scavenging reactive oxygen species in adipose tissue.

A visible light- and reactive oxygen species (ROS)-responsive pressure/strain sensor based on carbon dot (CD)-loaded conductive hydrogel was developed for detecting high-fat diet (HFD) and preventing the risk of non-alcoholic fatty liver disease. The designed nanoparticle consisted of a diselenide polymer dot (dsPD) loaded with a visible light-responsive CD to form dsPD@CD (DSCD). The influence of visible light irradiation and ROS on DSCD facilitated the electron transport, enhancing the conductivity of DSCD-embedded hydrogel (DSCD hydrogel) from 1.3 to 35.9 mS/m. Alternatively, the tensile modulus of the DSCD hydrogel enhanced to 223 % after light-induced ROS treatment, which simultaneously impacted the capacitive response (120 %). The hydrogel implantation into inguinal white adipose tissue of HFD mice showed 82 % higher conductivity and 83 % enhanced pressure sensing response to HFD-generated high ROS levels compared with the normal diet-fed mice. Additionally, the ROS scavenging activity of DSCD hydrogel was confirmed by the downregulation of ROS-responsive genes, such as Sod2, Nrf2, and catalase (Cat) in murine primary hepatocytes isolated from fatty liver-induced mice. In addition, in vivo animal studies also confirmed the suppression of hepatic lipogenesis, as shown by decreased Pparγ and Fasn expression and hypertrophy of adipocytes in HFD mice. The distinguishable real-time wireless resistance response observed with pressure sensing indicates the potential application of the device for monitoring the risk of non-alcoholic fatty liver disease. STATEMENT OF SIGNIFICANCE: A visible-light-induced ROS-responsive carbon dot-loaded conductive hydrogel was developed for the detection of HFD-induced alterations in ROS levels by evaluating the conductivity and electrochemical responses with applied pressure/strain. The implanted hydrogel facilitates the recovery of the inflated adipocytes induced by NAFLD, which reduces fat accumulation in the liver, preventing the risk of NAFLD. Real-time detection based on the resistance response during local compression of the hydrogel is possibly performed utilizing a wireless sensing device, demonstrating the ease of NAFLD monitoring.

In Situ Cancer-Cell-Triggered Visible Changes in Mechanical Properties, Electroconductivity, and Adhesiveness of a MnO2@PD-Based Mineralized Hydrogel.

Herein, a cancer-specific dopamine-conjugated sp2-rich carbonized polymer dot (PD)-encapsulated mesoporous MnO2 (MnO2@PD)-mineralized hydrogel biosensor was developed that offers cancer-induced observable in situ alterations in fluorescence (FL), electrochemical, and mechanophysical properties. Cancer-triggered MnO2 degradation in the hydrogel, prompted by increased levels of glutathione (GSH) and reactive oxygen species (ROS) such as H2O2, leads to PD release and FL restoration, thereby controlling changes in the pore structure and increasing hydrogen bonding, resulting in physiologically visible alterations in mechanical stretchability, viscosity, swelling behavior, and adhesiveness. The pore size of the matrix increased from 21.83 to 36.81 m2/g upon GSH treatment, affecting the viscosity and swellability of the system. The resistance increased from 21.96 ± 1.16 to 30.69 ± 2.01 and 32.21 ± 2.54 kΩ, respectively, confirming the dependence of conductivity changes on H2O2 and GSH treatments. The in vitro treatment with cancer cells (HeLa, PC-3, and B16F10) facilitated a tunable electrochemical sensing performance via redox-mediated MnO2 breakdown by intracellular ROS and GSH, whereas hydrogels treated with normal cells (CHO-K1) showed minimal changes. Cancer-microenvironment-derived water-drop sensing showed three times higher response as compared to the normal cell-treated hydrogel. The sensing capability of the fabricated sensor was validated based on bending-induced relative resistance changes under dry and wet conditions. Moreover, the integration of the developed sensor with a wireless sensor enabled real-time monitoring with a smartphone.

Protection and Restoration of Damaged Hair via a Polyphenol Complex by Promoting Mechanical Strength, Antistatic, and Ultraviolet Protection Properties.

In this study, we developed a hair-coating polyphenol complex (PPC) that showed ultraviolet (UV) protection properties, antistatic features, and the capability to enhance the mechanical strength of damaged hair. PPCs prepared with different ratios of tannic acid (TA), gallic acid (GA), and caffeic acid (CA) simultaneously increased the self-recovery of damaged hair by protecting the cuticle. PPC prevented light from passing through the damaged hair during exposure to UV radiation. Moreover, surfaces coated with PPC1 (TA:GA:CA, 100:20:0.5) exhibited a higher conductivity than surfaces coated with PPCs with other ratios of TA, GA, and CA, with a resistance of 0.72 MΩ. This influenced the antistatic performance of the surface, which exhibited no electrical attraction after being subjected to an electrostatic force. Additionally, damaged hair exhibited a significant increase in durability and elasticity after coating with a PPC1-containing shampoo, with a tensile strain of up to 2.06× post-treatment, indicating the recovery of the damaged cuticle by the PPC complex. Furthermore, PPC1-containing shampoo prevented damage by scavenging excess reactive oxygen species in the hair. The combination effect promoted by the natural PPC offers new insights into hair treatment and paves the way for further exploration of hair restoration technology.

Electrochemical and fluorescent dual-mode sensor of acetylcholinesterase activity and inhibition based on MnO2@PD-coated surface.

We developed an electrochemical and fluorescent dual-mode sensor for assessing acetylcholinesterase (AChE) activity and inhibition by taking advantage of the high redox sensitivity of surface-coated mesoporous MnO2@polymer dot (MnO2@PD) towards AChE. The following phenomena constitute the basis of the detection mechanism: fluorescence resonance energy transfer (FRET) effect between MnO2 and PD; catalytic hydrolysis of acetylthiocholine (ATCh) to thiocholine (TCh) by AChE expressed by PC-12 cells, inducing fluorescence restoration and change in the conductivity of the system due to MnO2 decomposition; the presence of the inhibitor neostigmine preventing the conversion of ATCh to TCh. The surface-coated biosensor presents both fluorescence-based and electrochemical approaches for effectively monitoring AChE activity and inhibition. The fluorescence approach is based on the fluorescent "on/off" property of the system caused by MnO2 breakdown after interaction with TCh and the subsequent release of PDs. The conductivity of the coated electrode decreased dramatically as AChE concentration increased, resulting in electrochemical sensing of AChE activity and inhibition screening. Real-time wireless sensing can be conducted using a smartphone to monitor the resistance change, investigating the potential use of MnO2@PD nanocomposites in biological studies, and offering a real-time redox-fluorescent test for AChE activity monitoring and inhibitor screening.

Area light source-triggered latent angiogenic molecular mechanisms intensify therapeutic efficacy of adult stem cells.

Light-based therapy such as photobiomodulation (PBM) reportedly produces beneficial physiological effects in cells and tissues. However, most reports have focused on the immediate and instant effects of light. Considering the physiological effects of natural light exposure in living organisms, the latent reaction period after irradiation should be deliberated. In contrast to previous reports, we examined the latent reaction period after light exposure with optimized irradiating parameters and validated novel therapeutic molecular mechanisms for the first time. we demonstrated an organic light-emitting diode (OLED)-based PBM (OPBM) strategy that enhances the angiogenic efficacy of human adipose-derived stem cells (hADSCs) via direct irradiation with red OLEDs of optimized wavelength, voltage, current, luminance, and duration, and investigated the underlying molecular mechanisms. Our results revealed that the angiogenic paracrine effect, viability, and adhesion of hADSCs were significantly intensified by our OPBM strategy. Following OPBM treatment, significant changes were observed in HIF-1α expression, intracellular reactive oxygen species levels, activation of the receptor tyrosine kinase, and glycolytic pathways in hADSCs. In addition, transplantation of OLED-irradiated hADSCs resulted in significantly enhanced limb salvage ratio in a mouse model of hindlimb ischemia. Our OPBM might serve as a new paradigm for stem cell culture systems to develop cell-based therapies in the future.

Enhancing Light Absorption and Prolonging Charge Separation in Carbon Quantum Dots via Cl-Doping for Visible-Light-Driven Photocharge-Transfer Reactions.

Limited light absorption beyond the UV region and rapid photocarrier recombination are critical impediments for the improved photocatalytic performance of carbon quantum dots (CQDs) under visible-light irradiation. Herein, we demonstrate single-step microwave-assisted syntheses of O-CQDs (typical CQDs terminated by carboxylic and hydroxyl functional groups) from a sucrose precursor and Cl-doped CQDs (Cl-CQDs) from a sucralose precursor in short reaction times and without using obligatory strong acids for Cl doping. The doping of Cl into the CQDs is observed to widen the absorption range and facilitate an enhanced separation of photoexcited charge carriers, which is confirmed by the results of optical absorption, photothermal response, and pump-probe ultrafast transient absorption spectroscopy measurements of the O-CQDs and Cl-CQDs. The photoexcited charge carriers with their longer lifetimes in Cl-CQDs enabled the quick degradation of methylene blue dye, rapid conversion of Ag+ ions to metallic Ag nanoparticles on the CQD surfaces, and reduction of GO to a well-dispersed rGO through the photoelectron transfer reactions under visible-light irradiation. The facile Cl doping strategy, hybridization of Ag nanoparticles or rGO to CQDs, and the elevated charge separation mechanism would open up new avenues in designing CQD-based materials for futuristic applications.

Real-Time Wireless Monitoring of Cell Proliferation and Detachment Based on pH-Responsive Conductive Polymer Dots.

In situ wireless monitoring for cell proliferation and detachment kinetics was conducted using pH-responsive zwitterionic polymer dots (Z-PDs), based on changes in electrochemical signals derived from Z-PD-coated substrates via the interaction of charges transferred between Z-PDs and cells. Z-PD-coated substrates were found to be a potent means to monitor and manipulate cell adhesion and detachment because of their high sensitivity over a wide range of pH conditions, and modification of the coated substrates was confirmed using a wireless system. At neutral pH, Z-PD-coated wireless sensors exhibited π-π stacking involving aromatic rings with hydrophobic interactions, thereby promoting cell proliferation; consequently, an increase in the measured resistance was observed. In contrast, Z-PD-coated substrates triggered by acidic and basic conditions promoted cell detachment, which induced an increase in the resistance compared with Z-PD substrates at pH 6.8, as a result of charges transferred to support Z-PD internalization through cell membranes after detachment. Therefore, as a wireless biosensor with excellent pH responsiveness that facilitates cell proliferation and detachment and whose electrochemical signals could be additionally acquired via a smartphone, Z-PD biosensors demonstrated a more favorable approach for monitoring cell-surface interactions than conventional optically based methods.

Tunable Pressure Sensor of f-Carbon Dot-Based Conductive Hydrogel with Electrical, Mechanical, and Shape Recovery for Monitoring Human Motion.

The reversible volume memories of the inner structures of soft materials with controllable hydrophilic-hydrophobic balance have been widely recognized, for example, hydrogels used in pressure sensors. Mechanical stimuli, such as pressure, vibration, and tensile, may influence the deformation of the hydrogel while simultaneously changing the electronic signal. Here, we designed a hydrophobic carbon dot nanoparticle (f-CD) mixed with polyvinyl alcohol and catechol-conjugated chitosan to obtain a hydrogel suitable for pressure and vibration sensor applications. The hydrophobicity of loaded f-CD plays an important role in mechanical performance and electronic signal acquisition. It also affects the different rheological reversibility and shape recovery as an impact on the volume transition. These characteristics are influenced by the compactness, dimensional structure, and density of the fabricated hydrogel. As a result, hydrogels with high hydrophobicity have a stiff structure (shear modulus 8123.1 N·m-2) compared to that of the hydrophilic hydrogel (ranging between 6065.7 and 7739.2 N·m-2). Moreover, the mechanically dependent volume transition hydrogel affects the electronic resistivity (up to 17.3 ± 1.3%) and capacitance change (up to 145%) when compressed with different forces. The hydrogel with a controlled hydrophobic-hydrophilic inner structure shows a unique sensitivity and great potential for various applications in wearable electronic skins, real-time clinical health-care monitoring, and human-computer interactions.

NIR-vis-Induced pH-Sensitive TiO2 Immobilized Carbon Dot for Controllable Membrane-Nuclei Targeting and Photothermal Therapy of Cancer Cells.

This study investigated a selective and sensitive theragnosis system for the specific targeting of the membrane and nuclei based on visible-light and pH-responsive TiO2-integrated cross-linked carbon dot (C-CD/TiO2) for tumor detection and controllable photothermal therapy. The cross-linking system was formed by boronate ester linkages between the TiO2-immobilized Dopa-decyl (D-CD) and zwitterionic-formed CD (Z-CD) for nuclear targeting, which showed fluorescence "off" at physiological pH. The fluorescence recovered to the "on" state in acidic cancer cells owing to cleavages of the boronate ester bonds, resulting in the disruption of the Förster resonance energy transfer that generated different CDs useful for tumor-selective biosensors and therapy. D-CD, which is hydrophobic, can penetrate the hydrophobic sites of the cell membrane; it caused a loss in the hydrophobicity of these sites after visible-light irradiation. This was achieved by the photocatalytic activity of the TiO2 modulating energy bandgap, whereas the Z-CD targeted the nucleus, as confirmed by merged confocal microscopy images. D-CD augmented by photothermal heat also exhibited selective anticancer activity in the acidic tumor condition but showed only minimal effects at a normal site at pH 7.4. After C-CD/TiO2 injection to an in vivo tumor model, C-CD/TiO2 efficiently ablated tumors under NIR light irradiation. The C-CD/TiO2 group showed up-regulation of the pro-apoptotic markers such as P53 and BAX in tumor. This material exhibited its potential as a theragnostic sensor with excellent biocompatibility, high sensitivity, selective imaging, and direct anticancer activity via photothermal therapy.

Construction of FeCo2O4@N-Doped Carbon Dots Nanoflowers as Binder Free Electrode for Reduction and Oxidation of Water.

Electrochemical water splitting is known as a potential approach for sustainable energy conversion; it produces H2 fuel by utilizing transition metal-based catalysts. We report a facile synthesis of FeCo2O4@carbon dots (CDs) nanoflowers supported on nickel foam through a hydrothermal technique in the absence of organic solvents and an inert environment. The synthesized material with a judicious choice of CDs shows superior performance in hydrogen and oxygen evolution reactions (HER and OER) compared to the FeCo2O4 electrode alone in alkaline media. For HER, the overpotential of 205 mV was able to produce current densities of up to 10 mA cm-2, whereas an overpotential of 393 mV was needed to obtain a current density of up to 50 mA cm-2 for OER. The synergistic effect between CDs and FeCo2O4 accounts for the excellent electrocatalytic activity, since CDs offer exposed active sites and subsequently promote the electrochemical reaction by enhancing the electron transfer processes. Hence, this procedure offers an effective approach for constructing metal oxide-integrated CDs as a catalytic support system to improve the performance of electrochemical water splitting.

Mineralized Soft and Elastic Polymer Dot Hydrogel for a Flexible Self-Powered Electronic Skin Sensor.

We propose an integrated, self-powered, flexible electronic skin device containing an alginate-derived polymer dot (A-PD)-incorporated mineralized hydrogel-based energy storage unit and a chitosan-derived n-type carbon dot (N-CD)-based solar cell for an energy-harvesting unit. This study demonstrates a unique architecture of mineralized hydrogel comprising A-PD-incorporated poly(acrylic acid) (PAA)/CaCO3/laponite containing soft and sensitive layers, deposited with a polyaniline electrode to serve as an energy storage unit. The self-assembly was achieved through the ionic cross-linking between A-PD and PAA driven by the mineralization process, resulting in excellent dimensional stability and improved mechanical properties of the hydrogel. The sp2 carbon-rich A-PD enhances the electrochemical performance and the overall photon-to-electrical conversion and storage efficiency for self-powered devices by the formation of the bridge of electrons between the ionized polymer and metal ion. The capacitive sensor developed in this study exhibits high sensitivity in detecting small pressure changes, such as the falling of small water droplets. The self-powered sensing device can detect and monitor various human motions continuously by harvesting light energy from outdoor sunlight. Furthermore, the energy-autonomous device exhibits unique responses for handwriting characters stably and repeatedly. The proposed system may be applicable to human-machine interfaces, biomonitoring systems, secure communication, and wearable devices.

Responsive polymers for medical diagnostics.

Stimulus-responsive polymers have been used in improving the efficacy of medical diagnostics through different approaches including enhancing the contrast in imaging techniques and promoting the molecular recognition in diagnostic assays. This review overviews the mechanisms of stimulus-responsive polymers in response to external stimuli including temperature, pH, ion, light, etc. The applications of responsive polymers in magnetic resonance imaging, capture and purification of biomolecules through protein-ligand recognition and lab-on-a-chip technology are discussed.

Diselenide-Bridged Carbon-Dot-Mediated Self-Healing, Conductive, and Adhesive Wireless Hydrogel Sensors for Label-Free Breast Cancer Detection.

Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp2 carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and in vivo cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.

Developing clinical cut-off scores for the university of California San Diego performance-based skills assessment in patients with schizophrenia.

This study aimed to obtain University of California San Diego Performance-based Skill Assessment (UPSA) cut-off scores for the purpose of severity classification and to expand the clinical utility of the UPSA for the evaluation of cognitive function in patients with schizophrenia. In total, 191 patients with schizophrenia were recruited. The UPSA, Positive and Negative Symptom Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and Global Assessment Functioning Scale (GAF) were used for the evaluation. The cognitive symptoms item of the CGI-SCH was used as a reference and the subjects were divided into three groups: mild, moderate, and severe. The sensitivity and specificity of the UPSA were analyzed by receiver operating characteristic curves. There were significant differences in the UPSA, CGI-SCH, PANSS, and GAF scores among the groups. In the mild and moderate groups, a UPSA score of 59 was identified as the optimal cut-off score, and a score of 41 was identified as the optimal cut-off score in the moderate and severe groups. Severity can be classified using the UPSA score as follows: ≥ 60 for mild, 41-59 for moderate, and ≤ 40 for severe. The UPSA could be used to assess the degree of daily living dysfunction in patients with schizophrenia.

Novel luciferase-opsin combinations for improved luminopsins.

Previous work has demonstrated that fusion of a luciferase to an opsin, to create a luminescent opsin or luminopsin, provides a genetically encoded means of manipulating neuronal activity via both chemogenetic and optogenetic approaches. Here we have expanded and refined the versatility of luminopsin tools by fusing an alternative luciferase variant with high light emission, Gaussia luciferase mutant GLucM23, to depolarizing and hyperpolarizing channelrhodopsins with increased light sensitivity. The combination of GLucM23 with Volvox channelrhodopsin-1 produced LMO4, while combining GLucM23 with the anion channelrhodopsin iChloC yielded iLMO4. We found efficient activation of these channelrhodopsins in the presence of the luciferase substrate, as indicated by responses measured in both single neurons and in neuronal populations of mice and rats, as well as by changes in male rat behavior during amphetamine-induced rotations. We conclude that these new luminopsins will be useful for bimodal opto- and chemogenetic analyses of brain function.

Live-cell imaging of single mRNA dynamics using split superfolder green fluorescent proteins with minimal background.

The MS2 system, with an MS2 binding site (MBS) and an MS2 coat protein fused to a fluorescent protein (MCP-FP), has been widely used to fluorescently label mRNA in live cells. However, one of its limitations is the constant background fluorescence signal generated from free MCP-FPs. To overcome this obstacle, we used a superfolder GFP (sfGFP) split into two or three nonfluorescent fragments that reassemble and emit fluorescence only when bound to the target mRNA. Using the high-affinity interactions of bacteriophage coat proteins with their corresponding RNA binding motifs, we showed that the nonfluorescent sfGFP fragments were successfully brought close to each other to reconstitute a complete sfGFP. Furthermore, real-time mRNA dynamics inside the nucleus as well as the cytoplasm were observed by using the split sfGFPs with the MS2-PP7 hybrid system. Our results demonstrate that the split sfGFP systems are useful tools for background-free imaging of mRNA with high spatiotemporal resolution.