3D Printing of Capacitive Pressure Sensors with Tuned Wide Detection Range and High Sensitivity Inspired by Bio-Inspired Kapok Structures.

Flexible pressure sensors have drawn considerable attention for their potential applications as electronic skins with both sensitivity and pressure response range. Although the introduction of surface microstructures effectively enhances sensitivity, the confined volume of their compressible structures results in a limited pressure response range. To address this issue, a biomimetic kapok structure is proposed and implemented for constructing the dielectric layer of flexible capacitive pressure sensors employing 3D printing technology. The structure is designed with easily deformable concave and rotational structures, enabling continuous deformation under pressure. This design results in a significant expansion of the pressure response range and improvement in sensitivity. Further, the study purposively analyses crucial parameters of the devised structure that affect its compressibility and stability. These include the concave angle θ, height ratio d1/d2, rotation angle α, and width k. As a result, the ultimate pressure sensors demonstrate remarkable features such as high sensitivity (≈2.38 kPa-1 in the range of 0-10 kPa), broad detection range (734 kPa), fast response time (23 ms), and outstanding pressure resolution (0.4% at 500 kPa). This study confirms the viability of bionic structures for flexible sensors, and their potential to expand the scope of wearable electronic devices.

Discovery of Potent SOS1 PROTACs with Effective Antitumor Activities against NCI-H358 Tumor Cells In Vitro/In Vivo.

Directly targeted KRAS inhibitors are now facing resistance problems, which might be partially solved by the combination of SOS1 inhibitors with KRAS inhibitors. However, this combination may still have some resistance mitigation potential. Comparatively, SOS1 PROTAC may have promising applications in addressing the drug resistance problem by degrading the SOS1 protein. Herein, we report the discovery of novel SOS1 PROTACs and their antitumor activity both in vitro and in vivo. In vitro studies demonstrated that degrader 4 had strong inhibitory effects on the proliferation of NCI-H358 cells with IC50 of 5 nM, together with significant degradation of SOS1 protein with DC50 of 13 nM. In the NCI-H358 xenograft model, degrader 4 exhibited significant antitumor activities with TGITV values of 58.8% at 30 mg/kg bid. The PK and safety profiles also supported degrader 4 for further studies as an effective tool compound.

Construction Strategy of Functionalized Liposomes and Multidimensional Application.

Liposomes are widely used in the biological field due to their good biocompatibility and surface modification properties. With the development of biochemistry and material science, many liposome structures and their surface functional components have been modified and optimized one by one, pushing the liposome platform from traditional to functionalized and intelligent, which will better satisfy and expand the needs of scientific research. However, a main limiting factor effecting the efficiency of liposomes is the complicated environmental conditions in the living body. Currently, in order to overcome the above problem, functionalized liposomes have become a very promising strategy. In this paper, binding strategies of liposomes with four main functional elements, namely nucleic acids, antibodies, peptides, and stimuli-responsive motif have been summarized for the first time. In addition, based on the construction characteristics of functionalized liposomes, such as drug-carrying, targeting, long-circulating, and stimulus-responsive properties, a comprehensive overview of their features and respective research progress are presented. Finally, the paper critically presents the limitations of these functionalized liposomes in the current applications and also prospectively suggests the future development directions, aiming to accelerate realization of their industrialization.

Efficient Visible-Light-Activated Ultra-Long Room-Temperature Phosphorescence Triggered by Multi-Esterification.

The development of ultra-long room-temperature phosphorescence (UL-RTP) in processable amorphous organic materials is highly desirable for applications in flexible displays, anti-counterfeiting, and bio-imaging. However, achieving efficient UL-RTP from amorphous materials remains a challenging task, especially with activation by visible light and a bright afterglow. Here we report a general and rational molecular-design strategy to enable efficient visible-light-excited UL-RTP by multi-esterification of a rigid large-plane phosphorescence core. Notably, multi-esterification minimizes the aggregation-induced quenching and accomplishes a 'four birds with one stone' possibility in the generation and radiation process of UL-RTP: i) shifting the excitation from ultraviolet light to blue-light through enhancing the transition dipole moment of low-lying singlet-states, ii) facilitating the intersystem crossing process through the incorporation of lone-pair electrons, iii) boosting the decay process of long-lived triplet excitons resulting from a significantly increased transition dipole moment, and iv) reducing the intrinsic triplet nonradiative decay by substitution of high-frequency vibrating hydrogen atoms. All these factors synergistically contribute to the most efficient and stable visible-light-stimulated UL-RTP (lifetime up to 2.01 s and efficiency up to 35.4 % upon excitation at 450 nm) in flexible films using multi-esterified coronene, which allows high-tech applications in single-component time-delayed white light-emitting diodes and information technology based on flashlight-activated afterglow encryption.

Value of growth arrest lines for predicting treatment effect on children with distal tibial epiphysis fractures.

Objective: This study aims to explore whether growth arrest lines can predict epiphyseal fracture healing. Method: The data of 234 children with distal tibial epiphysis fractures treated in our hospital from February 2014 to February 2022 were retrospectively analyzed. Imaging data were examined to record epiphyseal grade, fracture type, and the time to appearance of growth arrest lines. Follow-up data were retrieved to record treatment results (i.e., malunion, premature closure, or bone bridge formation). Results: There was a significant difference in the time to appearance of growth arrest lines between patients with epiphyseal grade 0-1 and grade 2-3 (P < 0.05) and between patients with normal healing and patients with a bone bridge (P < 0.05). Among patients with normal healing, there were no significant differences in the time to appearance of growth arrest lines between men and women and between patients with and without surgery (P > 0.05). There was a significant difference in the time to appearance of growth arrest lines between patients with different Salter-Harris fracture types (P < 0.05). Conclusion: For patients with epiphyseal grade 0-1, the time to appearance of growth arrest lines could be useful for predicting the treatment result of a distal tibial epiphyseal fracture.

Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy.

Luminogens characteristic of aggregation-induced emission (AIEgens) have been extensively exploited for the development of imaging-guided photodynamic therapeutic (PDT) agents. However, intramolecular rotation of donor-acceptor (D-A) type AIEgens favors non-radiative decay of photonic energy which results in unsatisfactory fluorescence quantum and singlet oxygen yields. To address this issue, we developed several molecularly engineered AIEgens with partially "locked" molecular structures enhancing both fluorescence emission and the production of triplet excitons. A triphenylphosphine group was introduced to form a D-A conjugate, improving water solubility and the capacity for mitochondrial localization of the resulting probes. Experimental and theoretical analyses suggest that the much higher quantum and singlet oxygen yield of a structurally "significantly-locked" probe (LOCK-2) than its "partially locked" (LOCK-1) and "unlocked" equivalent (LOCK-0) is a result of suppressed AIE and twisted intramolecular charge transfer. LOCK-2 was also used for the mitochondrial-targeting, fluorescence image-guided PDT of liver cancer cells.

Deep-reinforcement-learning-based self-organization of freely undulatory swimmers.

It is fascinating that fish groups spontaneously form different formations. The collective locomotions of two and multiple undulatory self-propelled foils swimming in a fluid are numerically studied and the deep reinforcement learning (DRL) is applied to control the locomotion. We explored whether typical patterns emerge spontaneously under the driven two DRL strategies. One strategy is that only the following fish gets hydrodynamic advantages. The other is that all individuals in the group take advantage of the interaction. In the DRL strategy, we use swimming efficiency as the reward function, and the visual information is included. We also investigated the effect of involving hydrodynamic force information, which is an analogy to that detected by the lateral line of fish. Each fish can adjust its undulatory phase to achieve the goal. Under the two strategies, collective patterns with different characteristics, i.e., the staggered-following, tandem-following phalanx and compact modes emerge. They are consistent with the results in the literature. The hydrodynamic mechanism of the above high-efficiency collective traveling modes is analyzed by the vortex-body interaction and thrust. We also found that the time sequence feature and hydrodynamic information in the DRL are essential to improve the performance of collective swimming. Our research can reasonably explain the controversial issue observed in the relevant experiments. The paper may be helpful for the design of bionic fish.

Water-soluble bright NIR AIEgens with hybrid ROS for wash-free mitochondrial "off-on" imaging and photodynamic therapy.

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission (φF = 17.8%) and high hybrid ROS productivity (including OH˙ and 1O2).

Pixelated Vacuum Flat Panel Detector Using ZnS Photoconductor and ZnO Nanowires Cold Cathode.

Vacuum flat panel detectors (VFPDs) using cold cathode have important applications in large-area photoelectric detection. Based on the electron-bombardment-induced photoconductivity (EBIPC) mechanism, the photoconductor-type VFPDs achieved high detection sensitivity. However, pixelated imaging devices have not yet been developed. In this paper, we fabricate a 4 × 7 pixel vacuum flat panel detector array made of ZnS photoconductor and ZnO nanowires cold cathode for an imaging application. The responsivity of the device and the pixel current uniformity are studied, and imaging of the patterned objects is achieved. Our results verify the feasibility of VFPDs for imaging.

Botulinum toxin A improves psychological distress in patients with hemifacial spasm.

OBJECTIVE: This study aimed at assessing mental health in patients with hemifacial spasm (HFS) and determined the effect of botulinum toxin type A (BTX-A) on psychological distress in patients with HFS. METHODS: Ninety-five HFS patients and 95 age- and sex-matched healthy controls were enrolled. Symptom checklist-90 (SCL-90) scores were used to measure psychological distress in HFS patients and healthy controls. The mental health status of HFS patients was also evaluated by SCL-90, before and after the injection of BTX-A. Moreover, for those patients with abnormal mental health, efficacy outcomes after treatment with BTX-A were compared with a propensity score-matched historical cohort without BTX-A treatment. RESULTS: The mean scores for interpersonal sensitivity, phobia, anxiety, depression, and somatization were significantly higher among HFS patients than healthy people (P < 0.05). There was no significant difference between female patients and male patients in HFS group (P > 0.05). There were significant improvements in somatization, interpersonal sensitivity, depression, anxiety, and phobia scores before and after treatment (P < 0.05). At 2 months, more patients experienced an improvement in psychological distress in the BTX-A group (61.29% versus 38.71%; P = 0.03). CONCLUSION: Patients with HFS are often accompanied by somatization, interpersonal sensitivity, depression, anxiety, and phobia. Our findings suggest that BTX-A can improve these symptoms. However, further well-designed prospective studies are warranted to validate our findings.

Fully Vacuum-Sealed Diode-Structure Addressable ZnO Nanowire Cold Cathode Flat-Panel X-ray Source: Fabrication and Imaging Application.

A fully vacuum-sealed addressable flat-panel X-ray source based on ZnO nanowire field emitter arrays (FEAs) was fabricated. The device has a diode structure composed of cathode panel and anode panel. ZnO nanowire cold cathodes were prepared on strip electrodes on a cathode panel and Mo thin film strips were prepared on an anode panel acting as the target. Localized X-ray emission was realized by cross-addressing of cathode and anode electrodes. A radiation dose rate of 10.8 µGy/s was recorded at the anode voltage of 32 kV. The X-ray imaging of objects using different addressing scheme was obtained and the imaging results were analyzed. The results demonstrated the feasibility of achieving addressable flat-panel X-ray source using diode-structure for advanced X-ray imaging.

A long-wavelength fluorescent probe with a large Stokes shift for lysosome-targeted imaging of Cys and GSH.

Biothiols including cysteine (Cys) and glutathione (GSH) are biological signaling molecules responsible for cell detoxification, cell metabolism and neutralization of reactive oxygen species. Here, we synthesized a long-wavelength fluorescent probe, DCIMA, for lysosome-targeted imaging of Cys and GSH in living cells. DCIMA is consisted of a dicyanoisophorone core modified with an acrylate group for biothiol detection through the Michael addition reaction and a morpholine group as the lysosome-targeting agent. The presence of the electron-donating morpholine group also enhances the intramolecular charge transfer mechanism of the probe, thereby enabling its long-wavelength fluorescence emission (670 nm) and large Stokes shift (180 nm). In concentration range of 0-30 µM, the probe was determined to react quickly with both Cys and GSH with low detection limits (<5 min, 35.2 nM for GSH and 34.8 nM for Cys) and achieve the sensitive fluorescence imaging of the biothiols located in the lysosomes of living cells.

The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value.

BACKGROUND: Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt-related transcription factor 2 (RUNX2) and OA risk. METHODS: The expression profile of RUNX2-derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA-miRNAs network. And then, the diagnostic value of RUNX2-derived circRNAs in OA was evaluated. RESULTS: RUNX2-derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR-498, miR-924, miR-361-3p, and miR-665). Bioinformatics analysis showed ECM-receptor interaction pathway ranked the most significant pathway of circ_RUNX2-miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. CONCLUSION: RUNX2-derived circ_RUNX2 may be involved in OA development via ECM-receptor interaction pathways and may be used as potential clinical indicator of OA.

Real-time detection and imaging of exogenous and endogenous Zn2+ in the PC12 cell model of depression with a NIR fluorescent probe.

Depression is closely related to overactivation of N-methyl-d-aspartic acid (NMDA) receptors, and Zn2+ is a vital NMDA receptor modulator involved in the pathophysiological and physiological processes of depression. Therefore, quantitative and real-time detection of Zn2+ is very important for understanding the pathogenesis of depression. In this work, a near-infrared (NIR) fluorescent probe ISO-DPA was designed and synthesized for Zn2+ detection with a large Stokes shift (185 nm), high quantum yield (up to 44%), high sensitivity (LOD = 0.106 µM) and good pH stability. The probe showed rapid response within 10 s, accompanied by a distinct fluorescence change from faint to bright pink with the fluorescence intensity increasing 4.5-fold. Moreover, the sensing mechanism of ISO-DPA towards Zn2+ was supported by MALDI-TOF-MS and Job's plot. The probe ISO-DPA could detect instantaneous variation of exogenous and endogenous Zn2+ in PC12 cells. The bioimaging results reveal the increase of the endogenous Zn2+ concentration in PC12 cells under the oxidative stress induced by glutamate and confirm that overactivation of NMDA receptors results in an increase of the Zn2+ level. All the results proved that ISO-DPA is an excellent probe for detecting Zn2+ in solution and living cells and could help us better understand Zn2+ associated pathogenesis of depression.

The Application of and Factors Influencing, the NB5 Assay in Neuroblastomas.

PURPOSE: The NB5 assay was performed in bone marrow (BM) and peripheral blood (PB) to detect neuroblastomas (NBs) with micrometastases. The sensitivity and factors influencing the NB5 assay were preliminarily evaluated. METHODS: The NB5 assay uses RT-PCR to detect the co-expression of five mRNAs from the neuroblastoma-associated genes, CHGA, DCX, DDC, PHOX2B, and TH. We enrolled 180 cases of neuroblastoma and 65 cases of non-neuroblastoma. Bone marrow and peripheral blood were collected from every patient. The gold standard for the diagnosis of NB was pathological evaluation of solid tumor specimens or bone marrow biopsies (BMBs) from hematological tumors. STATA version 15 and SPSS version 17 software were used for analysis. RESULTS: We found that 17 patients were BMB (+), and they were diagnosed as the International Neuroblastoma Staging System (INSS) stage IV and the high-risk group. All 17 patients were BM (+), while 15 patients were PB (+) (15/17, 88.2%). Among the 163 children who were BMB (-), 56 were BM (+), 40 were PB (+), and 36 were BM (+) and PB (+). The sensitivity of the NB5 assay in BM (40.5%) and PB (30.5%) was significantly higher than the sensitivity of BMB (9.4%, P = 0.000). In the non-NB group, four cases were BM (+) and one case was PB (+). The specificity of the NB5 assay in BM and PB was 93.8% and 98.5%, respectively. The sensitivity of the NB5 assay in both BM and PB in INSS stage IV patients was significantly higher than that in INSS stage I-II patients (P <0.05). The sensitivity of the NB5 assay in both BM and PB in the high-risk group was significantly higher than that in the middle-low-risk groups (P = 0.0001). Logistic regression analyses indicated that liver metastases and bone metastases were the primary factors influencing the sensitivity of the NB5 assay in BM and PB (P <0.05). CONCLUSIONS: The NB5 assay had significantly higher sensitivity than the pathological analysis of BMB in detecting NB with micrometastases. The NB5 assay had higher sensitivity in INSS stage IV or the high-risk group. Liver metastases and bone metastases were the primary factors that affected the sensitivity of the NB5 assay.

Long-Wavelength AIE-Based Fluorescent Probes for Mitochondria-Targeted Imaging and Photodynamic Therapy of Hepatoma Cells.

With this research, we have developed two long-wavelength theranostic probes (DCMT and DCMC) with aggregation-induced emission (AIE)-based properties for image-guided photodynamic therapy (PDT) of hepatoma cells. Introduction of a triphenylamine or carbazole group to a dicyanomethylene-4H-pyran dye with long-wavelength fluorescence emission produces the AIE-based probes, which were subsequently modified with triphenyl-phosphonium cation for actively targeting the mitochondria of hepatoma cells. Solution-based experiments show that the probes exhibit a mixed photophysical mechanism of twisted-intramolecular charge transfer and AIE at different aggregation states. The molecular aggregation of the probes also leads to an enhanced ability for oxygen photosensitization, suggesting their potential for PDT of cancer cells. Our subsequent cell-based assays show that the probes localize in the mitochondria of hepatoma cells and the use of light leads to cell death through the intracellular production of reactive oxygen species.

A subcellular level study of copper speciation reveals the synergistic mechanism of microbial cells and EPS involved in copper binding in bacterial biofilms.

The synergistic cooperation of microbial cells and their extracellular polymeric substances (EPS) in biofilms is critical for the biofilm's resistance to heavy metals and the migration and transformation of heavy metals. However, the effects of different components of biofilms have not been fully understood. In this study, the spatial distribution and speciation of copper in the colloidal EPS, capsular EPS, cell walls and membranes, and intracellular fraction of unsaturated Pseudomonas putida (P. putida) CZ1 biofilms were fully determined at the subcellular level. It was found that 60-67% of copper was located in the extracellular fraction of biofilms, with 44.7-42.3% in the capsular EPS. In addition, there was 15.5-20.1% and 17.2-21.2% of copper found in the cell walls and membranes or the intracellular fraction, respectively. Moreover, an X-ray absorption fine structure spectra analysis revealed that copper was primarily bound by carboxyl-, phosphate-, and hydrosulfide-like ligands within the extracellular polymeric matrix, cell walls and membranes, and intracellular fraction, respectively. In addition, macromolecule quantification, fourier-transform infrared spectroscopy spectra and sulfur K-edge x-ray absorption near edge structure analysis further showed the carboxyl-rich acidic polysaccharides in EPS, phospholipids in cell walls and cell membranes, and thiol-rich intracellular proteins were involved in binding of copper in the different components of biofilm. The full understanding of the distribution and chemical species of heavy metals in biofilms not only promotes a deep understanding of the interaction mechanisms between biofilms and heavy metals, but also contributes to the development of effective biofilm-based heavy metal pollution remediation technologies.

AND-Logic Based Fluorescent Probe for Selective Detection of Lysosomal Bisulfite in Living Cells.

Sulfur dioxide (SO2) plays significant roles in regulating cell apotosis and inflammation. However, there are complex interactions between small biomolecules in cells, and the identification of these coexisting biomarkers remains a challenge. Herein, we report an AND logic gate based fluorescent probe (NY-Lyso), operating by responding to pH differences between organelles in cell and selectively reacting with bisulfite (HSO3-). This approach allows the fluorescence of the probe to remain silent under neutral or alkaline conditions, notably, is activated by costimulation of lower pH and bisulfite. Furthermore, it was confirmed to be biocompatible and could be employed to monitor HSO3- in lysosomes of living cells. The proposed method demonstrated more practical and outstanding capabilities in targeted and real-time monitoring, providing an effective optical tool for biomarker sensing.

A near-infrared xanthene-based fluorescent probe for selective detection of hydrazine and its application in living cells.

Developing fluorescent probes for selective determination of the toxic and carcinogenic hydrazine are pretty significant. Herein, a rhodamine dye coupled to naphthalene was selected as a near-infrared fluorophore and acetyl group as a trigger unit for hydrazine sensing with a Stokes shifts of 62 nm. The probe showed about 77-fold NIR fluorescence enhancement in the presence of hydrazine. In addition, the detection limit was as low as 3.4 ppb, and the fluorescence intensity at 654 nm showed a satisfactory linearity with the concentration range of hydrazine from 0 to 120 µM. More importantly, the practical utility of probe has been successfully proved through the fluorescence bioimaging of hydrazine in living cells with low cytotoxicity and quantitative N2H4 detection in environmental water samples.

Mitochondria-Targeted Ratiometric Fluorescent Probe Based on Diketopyrrolopyrrole for Detecting and Imaging of Endogenous Superoxide Anion in Vitro and in Vivo.

Intracellular reactive oxygen species is involved in a wide variety of physiological and pathological processes. In this work, we have developed a new mitochondria-targeting probe (DPP-S) for superoxide anion detection with ratiometric fluorescence response. DPP-S exhibited an obvious color change from violet to orange along with a distinct fluorescence change with maximum emission peak from 652 to 545 nm in response to superoxide anion. The limit of detection of DPP-S for superoxide anion was calculated to be 20.5 nM. Imaging studies taken in MCF-7 and RAW264.7 cells showed that DPP-S could be employed as a ratiometric fluorescent probe for endogenous superoxide anion detection and imaging in living cells with a large emission shift. Furthermore, the colocalization study indicated that DPP-S can localize in mitochondria specifically. Finally, the fluorescent probe was successfully applied for superoxide anion imaging in mice.