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.

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.

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.

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 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.

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.

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.

Reaction-based fluorescent probe for the selective and sensitive detection of thiophenols with a large Stokes shift and its application in water samples.

Although widely used in organic synthesis, pharmaceuticals and agrochemicals, thiophenol has brought about a series of ecological problems due to its high toxicity. Therefore, the development of efficient methods to discriminate thiophenols from aliphatic thiols is of great importance. In this work, a new reaction-based turn-on red fluorescence probe for the detection of thiophenols has been developed for the first time by employing dicyanomethylene-4H-pyran (DCM) as a fluorescence reporter and 2,4-dinitrobenzene-sulfonate (DNBS) as a recognition unit. The probe displayed a highly selective and sensitive (63 fold-fluorescence enhancement) response to thiophenols over aliphatic thiols. Additionally, the probe also exhibited a large Stokes shift (159 nm) and the detection limit reached as low as 8.3 nM. Moreover, this probe was also proved suitable for the quantification of thiophenol in real environmental water samples.

Urethane tetrathiafulvalene derivatives: synthesis, self-assembly and electrochemical properities.

This paper reports the self-assembly of two new tetrathiafulvalene (TTF) derivatives that contain one or two urethane groups. The formation of nanoribbons was evidenced by scanning electron microscopy (SEM) and X-ray diffraction (XRD), which showed that the self-assembly ability of T 1 was better than that of T 2 . The results revealed that more urethane groups in a molecule did not necessarily instigate self-assembly. UV-vis and FTIR spectra were measured to explore noncovalent interactions. The driving forces for self-assembly of TTF derivatives were mainly hydrogen bond interactions and π-π stacking interactions. The electronic conductivity of the T 1 and T 2 films was tested by a four-probe method.

Intravitreal controlled release of dexamethasone from engineered microparticles of porous silicon dioxide.

Dexamethasone is a glucocorticoid that is widely used in the ophthalmic arena. The recent FDA approved dexamethasone implant can provide a three month efficacy but with high rate of drug related cataract and high intraocular pressure (IOP). It seems that higher steroid in aqueous humor and around lens may be associated with these complications based on clinical fact that higher IOP was observed with intravitreal triamcinolone acetonide (TA) than with subtenon TA. We hypothesize that placing a sustained dexamethasone release system near back of the eye through a fine needle can maximize efficacy while mitigate higher rate of IOP rise and cataract. To develop a sustained intravitreal dexamethasone delivery system, porous silicon dioxide (pSiO2) microparticles were fabricated and functionalized with amines as well as carboxyl groups. Dexamethasone was conjugated to pSiO2 through the Steglich Esterification Reaction between hydroxyl of dexamethasone and carboxyl groups on the pSiO2. The drug loading was confirmed by Fourier transform infrared spectroscopy (FTIR) and loading efficiency was quantitated using thermogravimetric analysis (TGA). In vitro release was conducted for three months and dexamethasone was confirmed in the released samples using liquid chromatography-tandem mass spectrometry (LC/MS/MS). A pilot ocular safety and determination of vitreous drug level was performed in rabbit eyes. The drug loading study demonstrated that loading efficiency was from 5.96% to 10.77% depending on the loading reaction time, being higher with longer loading reaction time before reaching saturation around 7 days. In vitro drug release study revealed that dexamethasone release from pSiO2 particles was sustainable for over 90 days and was 80 days longer than free dexamethasone or infiltration-loaded pSiO2 particle formulation in the same setting. Pilot in vivo study demonstrated no sign of ocular adverse reaction in rabbit eyes following a single 3 mg intravitreal injection and free drug level at 2-week was 107.23 ± 10.54 ng/mL that is well above the therapeutic level but only around 20% level of dexamethasone released from OZURDEX(®) (dexamethasone intravitreal implant) in a rabbit eye model. In conclusion, dexamethasone is able to covalently load to the pSiO2 particles and provide sustained drug release for at least 3 months in vitro. Intravitreal injection of these particles were well tolerated in rabbit eyes and free drug level in vitreous at 2-week was well above the therapeutic level.

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.

Prognostic Value of Magnetic Resonance Imaging Variables Combined with Neutrophil-to-Lymphocyte Ratio in Patients with Cervical Traumatic Spinal Cord Injury.

OBJECTIVE: We aimed to explore the prognostic significance of preoperative magnetic resonance imaging (MRI) variables and novel inflammatory indicators in predicting neurological recovery post-cervical traumatic spinal cord injury (TSCI) in the study. METHODS: We enrolled a total of 244 patients diagnosed with acute cervical TSCI from 2 hospitals and evaluated the prognostic value of MRI variables (intramedullary hemorrhage, intramedullary lesion length [IMLL], maximum spinal cord compression, and maximum canal compromise [MCC]) and novel inflammatory indicators (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and systemic immune-inflammatory index) in patients with acute cervical TSCI. RESULTS: Among the 244 patients, 140 (57.38%) exhibited improved AIS grade conversion at 1-year follow-up. The results revealed intramedullary hemorrhage, IMLL, MCC, neutrophils, and NLR were significantly different compared with follow-up AIS grade. Furthermore, IMLL, MCC, white blood cells, neutrophils, NLR, and lymphocyte-to-monocyte ratio correlated with the follow-up AIS grade by Spearman's correlation analysis. Multivariate analysis showed IMLL, intramedullary hemorrhage, NLR, and admission AIS grade emerged as independent predictors of AIS grade conversion. The receiver operating characteristic curve analysis showed that the novel model (combination of MRI variables, NLR, and admission AIS grade) produced a larger area under the curve compared with using only intramedullary hemorrhage, IMLL, NLR, or admission AIS grade individually. CONCLUSION: Intramedullary hemorrhage and IMLL and NLR are predictors of AIS grade conversion after cervical TSCI. Therefore, we suggest the combination of MRI variables and NLR for the prognostic prediction of AIS grade conversion in patients with cervical TSCI.

Fabrication of ZnO Nanowire Cold Cathode Flat-Panel X-ray Source with a Reflective Anode.

A novel reflective anode flat-panel X-ray source using ZnO nanowire cold cathode and a metal anode has been developed. Simulation analysis indicated that the reflective anode structure reduces electric field concentration compared to a transmission anode structure. The current-voltage characteristics, X-ray radiation dose rate, and stability of the fabricated device were thoroughly characterized. The device demonstrated a maximum emission current of 481.1 µA and a maximum radiation dose rate of 303 µGy/s at an anode voltage of 40 kV. The X-ray imaging of various objects was also conducted. Our findings are of significance for developing high-performance, robust flat-panel X-ray sources for diverse applications.

Trigger thresholds and their dynamics of vegetation production loss under different atmospheric and soil drought conditions.

Many evidences have shown that both atmospheric and soil droughts can constrain vegetation growth and further threaten its ability to sequester carbon. However, the trigger thresholds of vegetation production loss under different atmospheric and soil drought conditions are still unknown. In this study, we proposed a Copula and Bayesian equations-based framework to investigate trigger thresholds of various vegetation production losses under different atmospheric and soil drought conditions. The trigger thresholds dynamics and their possible causes were also investigated. To achieve this goal, we first simulated the gross primary production, soil moisture, and vapor pressure deficit over China during 1961-2018 using an individual-based, spatially explicit dynamic global vegetation model. The main drivers of the dynamic change in trigger thresholds were then explored by Random Forest model. We found that soil drought caused greater stress on gross primary production loss than atmospheric drought, with a larger impact area and higher probability of damage. In terms of spatial distribution, the risk probability of gross primary production loss was higher in eastern China than in western China, and the drought trigger threshold was also smaller in eastern China. In addition, the trigger thresholds for atmospheric and soil drought in most regions exhibited a decreasing trend from 1961 to 2018, while the CO2 fertilization enhanced the drought tolerance of vegetation. The reduction in CO2 fertilization effect slowed down the downward trend of trigger threshold for soil drought, while the increase in temperature exacerbated the downward trend of trigger threshold for atmospheric drought. This study highlighted the larger effect of soil drought on vegetation production loss than atmospheric drought and implied that climate change can modulate the trigger threshold of vegetation production losses under drought conditions. These findings provide scientific guidance for managing the increasing risk of drought on vegetation and optimizing watershed water allocation.

Bioaerosols emission from source facilities in a wastewater treatment plant: Critical exposure time and sensitivity analysis.

Overexposure of sewage workers to bioaerosol released from wastewater treatment plants (WWTPs) can cause serious infections, but practical method for controlling their health risk is lacking. In this study, reverse quantitative microbial risk assessment was used to estimate the daily critical exposure time (CET) of sewage workers exposing to Staphylococcus aureus bioaerosol emitted by three emission sources facilities in a WWTP based on either U.S. EPA or WHO benchmark, and sensitivity analysis was conducted to analyze the influence of various parameters on the outcomes of CET. The results showed that the CET of females was always 1.12-1.29 times that of males. In addition, the CET after wearing face masks was 28.28-52.37 times as long as before. The working time can be determined based on the CET results of male workers wearing face masks exposed to the inverted-umbrella aeration tank (14.73-550.98 min for U.S. EPA benchmark and 55.07-1972.24 min for WHO benchmark). In each scenario, the variable parameter exposure concentration (ec) always showed the most influence on the CET results. After wearing the face masks, the removal fraction by employing face masks also had a significant effect on the results, only second to ec. Therefore, the wearing of face mask is the most convenient and effective measure to prolong the CET. Furthermore, practical methods to reducing bioaerosol concentration in WWTPs exposure are also necessary to extend CET and safeguard worker health. This study enriches the application range of reverse quantitative microbial risk assessment framework and provides theoretical support for stakeholders to establish reasonable working time threshold guidelines, and practical method and novel perspective to protect the on-site health risks of sewage workers exposing to various facilities.

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.

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.

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.

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.

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).