Finely-Tuning Chemiluminescent Color of CdTe Nanocrystals and Its Application for Near-Infrared Semi-Automatic Immunoassay.

Chemiluminescence (CL), especially commercialized CL immunoassay (CLIA), is normally performed within the eye-visible region of the spectrum by exploiting the electronic-transition-related emission of the molecule luminophore. Herein, dual-stabilizers-capped CdTe nanocrystals (NCs) is employed as a model of nanoparticulated luminophore to finely tune the CL color with superior color purity. Initialized by oxidizing the CdTe NCs with potassium periodate (KIO4), intermediates of the reactive oxygen species (ROS) tend to charge CdTe NCs in both series-connection and parallel-connection routes and dominate the charge-transfer CL of CdTe NCs. The CdTe NCs/KIO4 system can exhibit color-tunable CL with the maximum emission wavelength shifted from 694 nm to 801 nm, and the red-shift span is over 100 nm. Both PL and CL of each of the CdTe NCs are bandgap-engineered; the change in the NCs surface state via CL reaction enables CL of each of the CdTe NCs to be red-shifted for ∼20 nm to PL, while the change in the NCs surface state via labeling CdTe NCs to secondary-antibody (Ab2) enables CL of the CdTe NCs-Ab2 conjugates to be red-shifted for another ∼20 nm to bare CdTe NCs. The CL of CdTe753-Ab2/KIO4 is ∼791 nm, which can perform near-infrared CL immunoassay and semi-automatically determined procalcitonin (PCT) on commercialized in vitro diagnosis (IVD) instruments.

Na-Ru bimetallic functional sites promote photo-driven CO2 directed conversion into CH4.

Recently, there has been a significant increase in interest in using photocatalysis for the energy conversion of polluting gases. In this research, sodium and ruthenium bimetallic functional sites co-modified bismuth tungstate (Ru/Na-Bi2WO6) nanoflower photocatalyst was synthesized via the hydrothermal method. The CO2 reduction products on the Bi2WO6 substrate were CO (1.66 µmol/g/h, 68 %) and CH4 (0.78 µmol/g/h, 32 %). After optimization, a significant change in the CO2 products of the Bi2WO6-based composite material was observed, with CO (0.61 µmol/g/h, 3.6 %) and CH4 (16.1 µmol/g/h, 96.4 %). Results showed that the dominance of CH4 as the main product in the Ru/Na-BWO system is attributed to the effective doping of Na, which generates impurity energy levels composed of oxygen vacancies, lowering the conduction band position of Bi2WO6, thereby suppressing CO generation, and enhancing CH4 selectivity by changing the CO2 activation pathway. The remarkable performance is ascribed to the synergized adsorption and activation of CO2 by the tandem Na+ sites and Ru0 sites. Specifically, the doped Na+ sites play a major role in promoting the adsorption CO2 molecules, while the Ru0 sites play a dominant role in facilitating the activation of the intermediates.

Genkwanin alleviates intervertebral disc degeneration via regulating ITGA2/PI3K/AKT pathway and inhibiting apoptosis and senescence.

Intervertebral disc degeneration (IVDD) is a progressive degenerative disease influenced by various factors. Genkwanin, a known anti-inflammatory flavonoid, has not been explored for its potential in IVDD management. This study aims to investigate the effects and mechanisms of genkwanin on IVDD. In vitro, cell experiments revealed that genkwanin dose-dependently inhibited Interleukin-1ß-induced expression levels of inflammatory factors (Interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2) and degradation metabolic protein (matrix metalloproteinase-13). Concurrently, genkwanin upregulated the expression of synthetic metabolism genes (type II collagen, aggrecan). Moreover, genkwanin effectively reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) pathways. Transcriptome sequencing analysis identified integrin α2 (ITGA2) as a potential target of genkwanin, and silencing ITGA2 reversed the activation of PI3K/AKT pathway induced by Interleukin-1ß. Furthermore, genkwanin alleviated Interleukin-1ß-induced senescence and apoptosis in nucleus pulposus cells. In vivo animal experiments demonstrated that genkwanin mitigated the progression of IVDD in the rat model through imaging and histological examinations. In conclusion, This study suggest that genkwanin inhibits inflammation in nucleus pulposus cells, promotes extracellular matrix remodeling, suppresses cellular senescence and apoptosis, through the ITGA2/PI3K/AKT, NF-κB and MAPK signaling pathways. These findings indicate that genkwanin may be a promising therapeutic candidate for IVDD.

Low-Triggering-Potential and Narrow-Potential-Window Electrochemiluminescence of Silver Nanoclusters for Gene Assay.

A low-triggering potential and a narrow-potential window are anticipated to decrease the electrochemical interference and cross talk of electrochemiluminescence (ECL). Herein, by exploiting the low oxidative potential (0.82 V vs Ag/AgCl) of dihydrolipoic acid-capped sliver nanoclusters (DHLA-AgNCs), a coreactant ECL system of DHLA-AgNCs/hydrazine (N2H4) is proposed to achieve efficient and oxidative-reduction ECL with a low-triggering potential of 0.82 V (vs Ag/AgCl) and a narrow-potential window of 0.22 V. The low-triggering-potential and narrow-potential-window nature of ECL can be primarily preserved upon labeling DHLA-AgNCs to probe DNA and immobilizing DHLA-AgNCs onto the Au surface via sandwiched hybridization, which eventually enables a selective ECL strategy for the gene assay at +0.82 V. This gene assay strategy can sensitively determine the gene of human papillomavirus from 10 to 1000 pM with a low limit of detection of 5 pM (S/N = 3) and would open a way to improve the applied ECL bioassay.

Enhancing the Consistency and Performance of Graphene-Based Devices via Al Intermediate-Layer-Assisted Transfer and Patterning.

Graphene has garnered widespread attention, and its use is being explored for various electronic devices due to its exceptional material properties. However, the use of polymers (PMMA, photoresists, etc.) during graphene transfer and patterning processes inevitably leaves residues on graphene surface, which can decrease the performance and yield of graphene-based devices. This paper proposes a new transfer and patterning process that utilizes an Al intermediate layer to separate graphene from polymers. Through DFT calculations, the binding energy of graphene-Al was found to be only -0.48 eV, much lower than that of PMMA and photoresist with graphene, making it easier to remove Al from graphene. Subsequently, this was confirmed through XPS analysis. A morphological characterization demonstrated that the graphene patterns prepared using the Al intermediate layer process exhibited higher surface quality, with significantly reduced roughness. It is noteworthy that the devices obtained with the proposed method exhibited a notable enhancement in both consistency and sensitivity during electrical testing (increase of 67.14% in temperature sensitivity). The low-cost and pollution-free graphene-processing method proposed in this study will facilitate the further commercialization of graphene-based devices.

Potential-selective electrochemiluminescence of AgInS2/ZnS nanocrystals and its immunoassay application.

Potential-selective electrochemiluminescence (ECL) with tunable maximum-emission-potential ranging from 0.95 to 0.30 V is achieved using AgInS2/ZnS nanocrystals, which is promising in the design of multiplexed bioassay on commercialized ECL setups. The model system AgInS2/ZnS/N2H4 exhibits efficient ECL around 0.30 V and can be exploited for sensitive immunoassays with less electrochemical interference and crosstalk.

Clinical Manifestation, Risk Factors, and Immune Checkpoint Inhibitor Rechallenge of Checkpoint Inhibitor-Associated Pneumonitis in Patients With Lung Cancer.

SUMMARY: Immune-related adverse effects can lead to damage to various systems of the body, checkpoint inhibitor-associated pneumonitis (CIP) is one of the potentially lethal immune-related adverse effects. However, evidence regarding the risk factors associated with CIP is limited. To timely and accurate identification and prompt treatment of CIP, understanding the risk factors for multimorbidity among diverse study populations becomes crucial. We retrospectively analyzed the clinical data of 1131 patients with lung cancer receiving immunotherapy to identify 110 patients with CIP, the clinical characteristics and radiographic features of patients with CIP were analyzed. A case-control study was subsequently performed to identify the risk factors of CIP. The median treatment cycle was 5 cycles and the median time to onset of CIP was 4.2 months. CIP was mainly grade I or II. Most cases improved after discontinuation of immune checkpoint inhibitors (ICIs) or hormone therapy. Severe CIP tended to occur earlier in comparison to mild to moderate cases. The recurrence rate was 20.6% in ICI-rechallenged patients, and patients with relapsed CIP were usually accompanied by higher-grade adverse events than at first onset. Among the 7 patients with relapse, ICI-associated deaths occurred in 2 patients (28.6%). For rechallenging with ICIs after recovery from CIP, caution should be practiced. Male [odds ratio (OR): 2.067; 95% CI: 1.194-3.579; P= 0.009], history of chest radiation (OR: 1.642; 95% CI: 1.002-2.689; P= 0.049) and underlying lung disease (OR: 2.347; 95% CI: 1.008-5.464; P=0.048) was associated with a higher risk of CIP.

Wet Chemical Synthesis of Ultrathin γ-Ga2O3 Quantum Wires Enabling Far-UVC Photodetection with Ultrahigh Selectivity and Sensitivity.

As compared to solar-blind ultraviolet (UV) photodetectors (PDs), far-UVC PDs not only show some irreplaceable advantages but also are more challenging to be developed. To solve this challenge, we report herein a soft template-assisted solvothermal route to synthesize ultrathin γ-Ga2O3 quantum wires (UQWs) with diameters down to 1-2 nm. These UQWs all exhibit a cluster-like absorption feature with a strong peak located between 190 and 230 nm and an edge below 250 nm, allowing highly selective absorption to far-UVC light. Notably, their normalized absorption coefficients were experimentally and theoretically confirmed to increase obviously with decreasing their diameters. Self-powered photoelectrochemical-type PDs based on Ga2O3 QWs of 1.7 nm diameter were therefore fabricated, exhibiting an excellent far-UVC detection performance with an unprecedented ultrahigh spectral selectivity (R210 nm/R250 nm = 452). As a proof of concept, this paper offers a new idea for developing ultrawide bandgap semiconductor materials and devices by leveraging a strong quantum confinement effect.

Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Linearization signal conditioning circuit for tri-axial micro-grating MOEMS accelerometer.

This paper proposes what we believe to be a novel linearization signal conditioning circuit for a tri-axial micro-grating micro-opto-electro-mechanical systems (MOEMS) accelerometer. The output of a micro-grating accelerometer varies as a sine/cosine function of the acceleration. The proposed circuit utilizes a subdivision interpolation technique to process these nonlinear intensity variations and render a linear digital output across the full range. Such a linearization circuit was achieved through a 90-degree phase-shift circuit, high-precision DC bias-voltage and subdivision interpolation circuits to reduce the influence of phase, magnitude, and offset errors of the sine-cosine signals on the interpolation factor, improving the resolution and accuracy of acceleration detection. Experimental results demonstrated that the micro-grating MOEMS accelerometer achieves a resolution of sub-mg, cross-axis errors of 3.57%, 1.22% and 0.89% for x-, y- and z-aixs, respectively. The bias instabilities and velocity random walks for the vertical and lateral accelerometer are superior to 26 µg and 38.7 µg/√Hz. The tri-axial micro-grating MOEMS accelerometer exhibits significant potential for applications requiring high sensitivity and large operation ranges, including the automotive industry and military equipment.

Design of High-Gain Antenna Arrays for Terahertz Applications.

A terahertz band (0.1-10 THz) has the characteristics of rich spectrum resources, high transmission speed, strong penetration, and clear directionality. However, the terahertz signal will suffer serious attenuation and absorption during transmission. Therefore, a terahertz antenna with high gain, high efficiency, and wide bandwidth is an indispensable key component of terahertz wireless systems and has become a research hotspot in the field of antennas. In this paper, a high-gain broadband antenna is presented for terahertz applications. The antenna is a three-layer structure, fed by a grounded coplanar waveguide (GCPW), using polytetrafluoroethylene (PTFE) material as the dielectric substrate, and the metal through-hole of the dielectric substrate forms a substrate-integrated waveguide (SIW) structure. The metal fence structure is introduced to reduce the coupling effect between the radiation patches and increase the radiation bandwidth and gain. The center frequency is 0.6366 THz, the operating bandwidth is 0.61-0.68 THz, the minimum value of the voltage standing wave ratio (VSWR) is 1.00158, and the peak gain is 13.14 dBi. In addition, the performance of the designed antenna with a different isolation structure, the length of the connection line, the height of the substrate, the radius of the through-hole, and the thickness of the patch is also studied.

Combined Displacement and Angle Sensor with Ultra-High Compactness Based on Self-Imaging Effect of Optical Microgratings.

In this paper, an ultracompact combined sensor for displacement and angle-synchronous measurement is proposed based on the self-imaging effect of optical microgratings. Using a two-grating structure, linear and angular displacement can be measured by detecting the change of phase and amplitude of the optical transmission, respectively, within one single structure in the meantime. The optically transmitted properties of the two-grating structure are investigated in both theory and simulation. Simulated results indicate that optical transmission changes in a sinusoidal relationship to the input linear displacement. Meanwhile, the amplitude of the curve decreases with an input pitch angle, indicating the ability for synchronous measurement within one single compact structure. The synchronous measurement of the linear displacement and the angle is also demonstrated experimentally. The results show a resolution down to 4 nm for linear displacement measurement and a maximum sensitivity of 0.26 mV/arcsec within a range of ±1° for angle measurement. Benefiting from a simple common-path structure without using optical components, including reflectors and polarizers, the sensor shows ultra-high compactness for multiple-degrees-of-freedom measuring, indicating the great potential for this sensor in fields such as integrated mechanical positioning and semiconductor fabrication.

Deterministic reprogramming of neutrophils within tumors.

Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1+ state. Reprogrammed dcTRAIL-R1+ neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.

Unsupervised spatially embedded deep representation of spatial transcriptomics.

Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR's ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).

Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway.

Osteoarthritis (OA) is a prevalent degenerative disease that impairs limb function, and its pathogenesis is closely related to inflammation. Sakuranetin (SK) is a cherry flavonoid phytoalexin with potent anti-inflammatory, anti-oxidant, and ant-ifungal properties. In recent studies, flavonoid and phytoalexin-related medicines have shown promise in the treatment of OA. However, the effects of SK on chondrocyte inflammation and the chondrogenesis process have remained unexplored, as have its functions in OA treatment. This study sought to confirm the therapeutic effects of SK in the OA rat model and reveal the potential mechanisms for protecting chondrocytes. The relevant mechanisms of SK were analyzed by network pharmacology analysis. Chondrocytes were subjected to IL-1ß intervention to simulate an inflammatory environment and received SK treatment. Then, anabolism, catabolism, and inflammatory markers were detected by western blot, qPCR, elisa, and immunofluorescence. Chondrogenic ability was evaluated by micromass and 3D culture assays. The rats were treated with destabilization of the medial meniscus (DMM) surgery to establish an OA model and SK intra-articular injections subsequently. Histological staining, immunohistochemistry, and micro-CT were performed to analyze the structural and morphological changes of cartilage and subchondral bone. In chondrocytes, IL-1ß treatment reduced chondrogenic ability, promoted catabolism, and exacerbated inflammation by triggering the PI3K/AKT/NF-κB pathway, whereas SK treatment partially rescued these negative effects. In vivo, SK treatment effectively alleviated the degeneration of cartilage and subchondral bone, thereby delaying the progression of OA. In summary, SK alleviates chondrocyte inflammation and promotes chondrogenesis by inhibiting the PI3K/AKT/NF-κB pathway, thereby improving OA progression.

Outcomes of Filtering Surgery Versus Clear Lens Extraction in Young Patients With Angle-Closure Glaucoma.

PURPOSE: To compare the effect of filtering surgery versus clear lens extraction in young patients with medically uncontrolled angle-closure glaucoma (ACG). DESIGN: Retrospective, nonrandomized, comparative, interventional study. METHODS: We reviewed the medical charts of patients with the following scenarios: (1) age ≤40 years; (2) diagnosis of ACG without cataract, including primary angle-closure glaucoma (PACG), nanophthalmic ACG, and ACG combined with retinal dystrophies; and (3) ACG undergoing filtering surgery or clear lens extraction. The main outcomes including intraocular pressure (IOP), number of medications, best-corrected visual acuity, and severe complications were extracted at the postoperative early (within 1 week) and late stage (>3 months) follow-up. RESULTS: Data from 160 eyes of 130 young patients with ACG were available. Eyes with 76 PACG, 12 nanophthalmic ACG, and 26 ACG with retinal diseases underwent filtering surgery, whereas eyes with 22 PACG, 12 nanophthalmic ACG, and 12 ACG with retinal diseases received clear lens extraction. Overall, filtering surgery and clear lens extraction resulted in significant but comparable IOP and drug reductions at the postoperative late stage in each ACG subgroup, with similar complete success rates between 2 treatments (all P > .05). Regarding the safety, filtering surgery and patients with retinal diseases were independent factors associated with postoperative malignant glaucoma (P < .05 in both multivariable logistic regression models). CONCLUSIONS: This study highlights that the efficacy of clear lens extraction is comparable to that of filtering surgery in medically uncontrolled ACG in young patients, but clear lens extraction is safer, especially for young patients with ACG comorbid with retinal diseases.

Application of Hospital-Community-Family "Trinity" Remote Rehabilitation Guidance Based on Internet + WeChat Platform in Patients with Stroke After Discharge.

Objective: To investigate the impact of an Internet + WeChat platform-based "trinity" remote rehabilitation model involving the hospital, community, and family on stroke patient rehabilitation nursing. Methods: 159 patients with stroke who were discharged from Beijing Luhe Hospital of Capital Medical University from January 1, 2018, to December 31, 2019, were selected and divided into a control group (79 cases) and an experimental group (80 cases) by the random drawing method. The control group was given routine nursing, and the experimental group was given remote rehabilitation nursing intervention by using the WeChat network platform based on the control group. Limb function [Fugl-Meyer Assessment Scale (FMA)] and activities of daily living [Modified Barthel Index (MBI)] were evaluated at enrollment and at the end of 3 months, 6 months and 12 months in both groups. The compliance and satisfaction surveys in the two groups were evaluated after 6 months and 12 months of intervention. Results: (1) Before the intervention, there was no statistical significance in FMA score between the two groups (t = 0.798, P > .05). After 3 months, 6 months and 12 months of intervention, the FMA score in the two groups was increased compared with that before intervention (t = 2.463, P < .05), and the FMA scores in the experimental group at the above time points were higher than those in the control group (ts = 7.057, 14.285, Ps < .05). (2) There was no statistical difference in MBI scores between the two groups before intervention (t = 0.798, P > .05). After 3 months, 6 months, and 12 months of intervention, the MBI score in the two groups was increased compared with that before intervention (t = 0.232, P < .05), and MBI scores in the experimental group at the above time points were higher compared to the control group (ts = 4.959, 8.842, 8.131, Ps < .05). (3) The compliance scores in the experimental group were higher than those in the control group after 6 months and 12 months of intervention (ts = 4.959, 8.842, 8.131, Ps < .05). (4) The satisfaction survey scores in the experimental group after 6 months and 12 months of intervention were higher than those in the control group (ts = 2.120 ~ 14.554, Ps < .05). Conclusion: The Hospital-community-family "trinity" stroke rehabilitation model on the WeChat network platform holds significant importance. Enhancing limb function and daily living for stroke patients improves their quality of life and lessens reliance on caregivers. This positively impacts both survivors' well-being and healthcare resources. Increased patient satisfaction and compliance suggest a potential revolution in post-stroke care, favoring a more patient-centered approach. Overall, this model has transformative potential for stroke treatment, offering holistic and patient-focused strategies. Its success promises better rehabilitation outcomes, patient satisfaction, and cost reduction, while paving the way for innovative research in stroke treatment and rehabilitation.

Sporopollenin exine capsules modulate the function of microglial cells.

Immune cells are the housekeepers of the human body. They protect the body from pathogens, cellular damage, and foreign matter. Proper activation of immune cells is of great significance to diseases such as infection, inflammation, and neurodegeneration. However, excessive activation of cells can be detrimental. An ideal biomaterial could enhance the cellular immune function without proinflammation. In this work, we used sporopollenin exine capsules (SEC) from pollen to promote functions of primary microglia, a typical resident immune cell of the brain. We found that microglia aggregated around SEC and did not undergo any proinflammation. SEC improved the viability, migration, phagocytosis, and anti-inflammatory ability of microglia. By exploring the underlying mechanism of microglial activation without the production of cytotoxic pro-inflammatory cytokines, we found that SEC protects microglia against inflammation induced by lipopolysaccharide (LPS), an immunostimulatory factor, through the toll-like receptor 4 (TLR4) signaling pathway in a myeloid differentiation factor 88-dependent manner. These findings might shed light on the potential application of SEC in microglia transplantation for treatment of microglia-associated degenerative central nervous system diseases.

[Exploratory study on quantitative analysis of nocturnal breathing patterns in patients with acute heart failure based on wearable devices].

Patients with acute heart failure (AHF) often experience dyspnea, and monitoring and quantifying their breathing patterns can provide reference information for disease and prognosis assessment. In this study, 39 AHF patients and 24 healthy subjects were included. Nighttime chest-abdominal respiratory signals were collected using wearable devices, and the differences in nocturnal breathing patterns between the two groups were quantitatively analyzed. Compared with the healthy group, the AHF group showed a higher mean breathing rate (BR_mean) [(21.03 ± 3.84) beat/min vs. (15.95 ± 3.08) beat/min, P < 0.001], and larger R_RSBI_cv [70.96% (54.34%-104.28)% vs. 58.48% (45.34%-65.95)%, P = 0.005], greater AB_ratio_cv [(22.52 ± 7.14)% vs. (17.10 ± 6.83)%, P = 0.004], and smaller SampEn (0.67 ± 0.37 vs. 1.01 ± 0.29, P < 0.001). Additionally, the mean inspiratory time (TI_mean) and expiration time (TE_mean) were shorter, TI_cv and TE_cv were greater. Furthermore, the LBI_cv was greater, while SD1 and SD2 on the Poincare plot were larger in the AHF group, all of which showed statistically significant differences. Logistic regression calibration revealed that the TI_mean reduction was a risk factor for AHF. The BR_ mean demonstrated the strongest ability to distinguish between the two groups, with an area under the curve (AUC) of 0.846. Parameters such as breathing period, amplitude, coordination, and nonlinear parameters effectively quantify abnormal breathing patterns in AHF patients. Specifically, the reduction in TI_mean serves as a risk factor for AHF, while the BR_mean distinguishes between the two groups. These findings have the potential to provide new information for the assessment of AHF patients.

Reduction-responsive polymeric micelles for trans-corneal targeted delivery of microRNA-21-5p and glaucoma-specific gene therapy.

The therapeutic value of microRNA (miRNA) for the treatment of glaucoma has become a focus of attention. However, naked miRNA cannot cross the corneal barrier and reach the target tissue by itself. Thus, the precise transport of miRNA to the target sites is key to the success of gene therapy. Herein, we selected a miRNA, namely miR-21-5p, based on its unique intraocular pressure (IOP) mechano-sensing property. Moreover, a biocompatible polymeric poly(L-lysine) (PLL) micelle conjugated with collagenase and ABCA1 antibody was judiciously constructed to achieve the trans-corneal and target delivery of miR-21-5p to the trabecular meshwork (TM) and Schlemm's canal (SC) tissues inside the eye. The topically administrated PLL micelles as an eye drop successfully crossed the cornea with the help of collagenase and then preferentially accumulated in the target TM/SC tissues under the guidance of the ABCA1 antibody. When endocytosed by TM/SC cells, the PLL micelles could be decomposed in the reductive lysosomal environment to release miR-21-5p for successfully lowering the IOP by activating the miR-21-5p/eNOS/MMP9 signaling axis, which will open new prospects for glaucoma-specific gene therapy.