Predictive Value of Smoking Index Combined with NT-proBNP for Patients with Pulmonary Hypertension Due to Chronic Lung Disease: A Retrospective Study.

Purpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity. Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤50 mmHg) and non-mild (PASP >50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve. Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628). Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.

A G-quadruplex/thioflavin T-based label-free biosensor to detect ClO- in stress-induced hypertension.

Hypochlorous acid (HClO), as an essential reactive oxygen species (ROS) in biological systems, plays a pivotal role in processes of physiology and pathology. Abnormal fluctuations in HClO concentration can lead to various diseases, such as inflammation, cardiovascular diseases, and neurodegeneration. Therefore, developing an approach to rapidly and sensitively quantify ClO- content is vital to biomedicine development and bioassays. Herein, we fabricated a novel "turn-on" label-free fluorescence DNA probe to specifically detect hypochlorite ion (ClO-) based on G-quadruplex formation. To this end, we designed a G-rich signal DNA sequence (S-DNA) and a block DNA sequence (B-DNA), followed by the introduction of ClO--responsive phosphorothioate (PS) into B-DNA. In the absence of ClO-, B-DNA hybridized with S-DNA, preventing G-quadruplex formation from S-DNA; this resulted in the relatively low fluorescence intensity of ThT. Once ClO- was added, the hydrolysis between PS and ClO- split the B-DNA into two fragments, resulting in B-DNA breaking away from S-DNA, allowing G-quadruplex formation from S-DNA and increasing the fluorescence intensity of ThT. Using this method, we can detect ClO- without the interference of additional reactive oxygen species. The detection limit of ClO- was as low as 10 nM. Furthermore, this method facilitates the detection of ClO- within the tissues of rats with stress-induced hypertension.

Experimental Ischemic Stroke Induces Secondary Bihemispheric White Matter Degeneration and Long-Term Cognitive Impairment.

Clinical studies have identified widespread white matter degeneration in ischemic stroke patients. However, contemporary research in stroke has predominately focused on the infarct and periinfarct penumbra regions. The involvement of white matter degeneration after ischemic stroke and its contribution to post-stroke cognitive impairment and dementia (PSCID) has remained less explored in experimental models. In this study, we examined the progression of locomotor and cognitive function up to 4 months after inducing ischemic stroke by middle cerebral artery occlusion in young adult rats. Despite evident ongoing locomotor recovery, long-term cognitive and affective impairments persisted after ischemic stroke, as indicated by Morris water maze, elevated plus maze, and open field performance. At 4 months after stroke, multimodal MRI was conducted to assess white matter degeneration. T2-weighted MRI (T2WI) unveiled bilateral cerebroventricular enlargement after ischemic stroke. Fluid Attenuated Inversion Recovery MRI (FLAIR) revealed white matter hyperintensities in the corpus callosum and fornix across bilateral hemispheres. A positive association between the volume of white matter hyperintensities and total cerebroventricular volume was noted in stroke rats. Further evidence of bilateral white matter degeneration was indicated by the reduction of fractional anisotropy and quantitative anisotropy at bilateral corpus callosum in diffusion-weighted MRI (DWI) analysis. Additionally, microglia and astrocyte activation were identified in the bilateral corpus callosum after stroke. Our study suggests that experimental ischemic stroke induced by MCAO in young rat replicate long-term cognitive impairment and bihemispheric white matter degeneration observed in ischemic stroke patients. This model provides an invaluable tool for unraveling the mechanisms underlying post-stroke secondary white matter degeneration and its contribution to PSCID.

Silver-coated hollow fiber surface plasmon resonance sensor for glucose detection with enhanced limit of detection.

A fiber-optic surface plasmon resonance (SPR) biosensor based on a silver-coated hollow fiber (HF) structure for glucose detection is presented. The sensor surface was immobilized with 4-mercaptophenylboronic acid (PMBA) acting as a glucose recognition monolayer. Then, gold nanoparticles (AuNPs) modified with 2-aminoethanethiol (2-AET) and PMBA were introduced onto the sensor surface after glucose was captured to enhance the wavelength shift of the SPR phenomenon excited by the light transmitted in the wall of the HF sensor. Instead of the conventional one-step sensitization pretreatment commonly used in the deposition process of silver films for fiber-optic SPR sensors, a sensitization-activation two-step activation method was adopted in the fabrication of the proposed sensor. Experiments for glucose detection were performed on the fabricated sensors in the concentration range of 1 nM-1 mM. Results showed that the sensor fabricated by the two-step activation method has a much larger shift of resonance wavelength than the sensor fabricated using the one-step sensitization method. The resonance wavelength shift was found to be linear to the logarithm of the concentration in the range of 1 nM-1 mM. The sensor achieved a limit of detection (LOD) of as low as 1 nM, which is at least an order of magnitude lower than that of other fiber-optic sensors for glucose detection reported previously. The presented HF glucose sensor has the potential for biosensing applications and provides a large reference value in the study of optical fiber SPR sensors for biosensing.

A defect-enriched PdMo bimetallene for ethanol oxidation reaction and 4-nitrophenol reduction.

A defect-enriched PdMo bimetallene (d-PdMo) was prepared by a one-pot wet chemical reaction followed by post-treatment of oxidative etching. The introduction of defects can tailor the electronic structure of PdMo bimetallene and the prepared d-PdMo bimetallene exhibited excellent performance in the ethanol oxidation reaction (EOR) and 4-nitrophenol (4-NP) reduction reaction.

Effective lung nodule detection using deep CNN with dual attention mechanisms.

Novel methods are required to enhance lung cancer detection, which has overtaken other cancer-related causes of death as the major cause of cancer-related mortality. Radiologists have long-standing methods for locating lung nodules in patients with lung cancer, such as computed tomography (CT) scans. Radiologists must manually review a significant amount of CT scan pictures, which makes the process time-consuming and prone to human error. Computer-aided diagnosis (CAD) systems have been created to help radiologists with their evaluations in order to overcome these difficulties. These systems make use of cutting-edge deep learning architectures. These CAD systems are designed to improve lung nodule diagnosis efficiency and accuracy. In this study, a bespoke convolutional neural network (CNN) with a dual attention mechanism was created, which was especially crafted to concentrate on the most important elements in images of lung nodules. The CNN model extracts informative features from the images, while the attention module incorporates both channel attention and spatial attention mechanisms to selectively highlight significant features. After the attention module, global average pooling is applied to summarize the spatial information. To evaluate the performance of the proposed model, extensive experiments were conducted using benchmark dataset of lung nodules. The results of these experiments demonstrated that our model surpasses recent models and achieves state-of-the-art accuracy in lung nodule detection and classification tasks.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Causal effects between gut microbiota and pulmonary arterial hypertension: A bidirectional Mendelian randomization study.

BACKGROUND: Multiple studies have highlighted a potential link between gut microbes and the onset of Pulmonary Arterial Hypertension (PAH). Nonetheless, the precise cause-and-effect relationship remains uncertain. OBJECTIVES: In this investigation, we utilized a two-sample Mendelian randomization (TSMR) approach to probe the presence of a causal connection between gut microbiota and PAH. METHODS: Genome-wide association (GWAS) data for gut microbiota and PAH were sourced from MiBioGen and FinnGen research, respectively. Inverse variance weighting (IVW) was used as the primary method to explore the causal effect between gut flora and PAH, supplemented by MR-Egger, weighted median (WM). Sensitivity analyses examined the robustness of the MR results. Reverse MR analysis was used to rule out the effect of reverse causality on the results. RESULTS: The results indicate that Genus Ruminococcaceae UCG004 (OR = 0.407, P = 0.031) and Family Alcaligenaceae (OR = 0.244, P = 0.014) were protective factors for PAH. Meanwhile Genus Lactobacillus (OR = 2.446, P = 0.013), Class Melainabacteria (OR = 2.061, P = 0.034), Phylum Actinobacteria (OR = 3.406, P = 0.010), Genus Victivallis (OR = 1.980, P = 0.010), Genus Dorea (OR = 3.834, P = 0.024) and Genus Slackia (OR = 2.622, P = 0.039) were associated with an increased Prevalence of PAH. Heterogeneity and pleiotropy were not detected by sensitivity analyses, while there was no reverse causality for these nine specific gut microorganisms. CONCLUSIONS: This study explores the causal effects of eight gut microbial taxa on PAH and provides new ideas for early prevention of PAH.

Genetic association analysis of dietary intake and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

BACKGROUND: IPF is a complex lung disease whose aetiology is not fully understood, but diet may have an impact on its development and progression. Therefore, we investigated the potential causal connection between dietary intake and IPF through TSMR to offer insights for early disease prevention recommendations. METHODS: The study incorporated 29 dietary exposure factors, oily fish intake, bacon intake, processed meat intake, poultry intake, beef intake, pork intake, lamb/mutton intake, non-oily fish intake, fresh fruit intake, cooked vegetable intake, baked bean intake, fresh tomato intake, tinned tomato intake, salad/raw vegetable intake, Fresh fruit intake, coffee intake, tea intake, water intake, red wine intake, average weekly beer plus cider intake, alcoholic drinks per week, cereal intake, bread intake, whole-wheat intake, whole-wheat cereal intake, cheese intake, yogurt intake, salt added to food and whole egg intake. The study explored the causal link between diet and IPF using TSMR analysis, predominantly the IVW method, and performed sensitivity analyses to validate the results. RESULT: The study revealed that consuming oily fish, yogurt, and dried fruits had a protective effect against IPF, whereas the consumption of alcoholic beverages and beef was linked to an increased risk of IPF. CONCLUSION: In this MR study, it was discovered that the consumption of oily fish, yogurt, and dried fruits exhibited a protective effect against IPF, whereas the intake of alcoholic beverages and beef was associated with an elevated risk of IPF. These findings underscore the significance of making informed and timely dietary decisions in IPF prevention.

Enhancing Overall Water Splitting via Anion and Cation Synergistical Modulation in NiS Amorphous Compound.

Designing and synthesizing cost-effective catalysts that exhibit excellent performance of both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is a formidable task in the field of electrocatalysis. Herein, we present a Fe- and P-codoped NiS amorphous film catalyst (FeNiSP) via meticulous control over the cations and anions of metal compounds. The doped Fe and P increases active sites, reduces charge transfer resistance, and modulates electronic structures of the NiS matrix. Leveraging these advantages, the FeNiSP showcases exceptional bifunctional activities of HER and OER, with remarkably low overpotentials of only 135 and 330 mV for achieving a current density of 100 mA·cm-2 during HER and OER, respectively. Additionally, a low cell voltage of 1.56 V at 10 mA·cm-2 was achieved when it was employed as both the anode and the cathode for water splitting. Finally, density function theory calculations further elucidate that the simultaneous presence of Fe and P in the NiS amorphous film catalyst leads to a decrease in the band center of S and Ni. This consequential effect maintains a balanced adsorption/desorption of protons and strengthened the adsorption of O-based intermediates on the surface of FeNiSP, subsequently contributing to the outstanding electrocatalytic HER and OER activities.

APOBEC3A suppresses cervical cancer via apoptosis.

Background: Family members of Apolipoprotein B mRNA-editing enzyme catalytic 3 (APOBEC3) play critical roles in cancer evolution and development. However, the role of APOBEC3A in cervical cancer remains to be clarified. Methods: We used bioinformatics to investigate APOBEC3A expression and outcomes using The Cancer Genome Atlas (TCGA)-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) dataset, GTEx, and GSE7803. Immunohistochemistry was then used to identify APOBEC3A's expression pattern. We performed Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays to measure proliferation, migration, invasion, and apoptosis, respectively, using the SiHa and HeLa cell lines transfected with APOBEC3A. BALB/c nude mice were used to investigate the effects of APOBEC3A in vivo. The phosphorylated gamma-H2AX staining assay was applied to measure DNA damage. RNA sequencing (RNA-Seq) was applied to explore APOBEC3A-related signaling pathways. Results: APOBEC3A was more significantly expressed in cancer tissues than in adjacent normal tissues. Higher expression of APOBEC3A was associated with better outcomes in TCGA-CESC and GTEx. Immunohistochemistry showed that the expression of APOBEC3A was significantly higher in cancer tissues than in normal tissues. Transfection experiments showed that APOBEC3A inhibited proliferation, upregulated S-phase cells, inhibited migration and invasion, induced DNA damage, and promoted apoptosis. Overexpression of APOBEC3A inhibited tumor formation in the mouse model. RNA-seq analysis showed that ectopic expression of APOBEC3A inhibited several cancer-associated signaling pathways. Conclusions: APOBEC3A is significantly upregulated in cervical cancer, and higher expression of APOBEC3A is associated with better outcomes. APOBEC3A is a tumor suppressor whose overexpression induces apoptosis in cervical cancer.

Design of flexible hollow core fiber based photoacoustic gas sensor with high cell constant and compact size.

Here we designed, optimized, and proposed a flexible low frequency resonant photoacoustic (PA) gas sensor by using a large core leaky hollow core fiber (L-HCF). The influences from the dimensions, the transmission loss and the bending loss on the performance of the flexible PA gas sensor were systematically investigated. In this work, the optimized inner diameter and length of the L-HCF were 1.7 mm and 300 mm, respectively. The L-HCF based PA cell constant was calculated to be 12115 Pa/(W·cm-1). The minimum detectable limit (MDL) for trace C2H2 detection achieved 23.0 ppb when the lock-in integration time was 200 s by using a near-infrared distributed feedback (DFB) laser source and a low-cost electrical micro-electro-mechanical system (MEMS) microphone. Besides, the amplitude decay ratio of the of the PA signal was only 11.3% when the bending radius of the L-HCF was 100 mm. The normalized noise equivalent absorption (NNEA) coefficient is calculated to be 6.6 × 10-9 W•cm-1•Hz-1/2. The L-HCF based PA cell was proved to own merits of compact size, high cell constant, small gas volume and low cost.

Long-range surface plasmon resonance-based hollow fiber temperature sensor with ultrahigh sensitivity and tunable detection range.

A dielectric/Ag-coated hollow fiber (HF) temperature sensor based on long-range surface plasmon resonance (LRSPR) is proposed and experimentally demonstrated. The structural parameters, including the dielectric material and layer thicknesses, are optimized through comprehensive theoretical analysis to achieve the best performance. By filling it with a high refractive index (RI) thermosensitive liquid, the GK570/Ag-coated HF temperature sensor with optimal structural parameters is fabricated. Due to the high sensitivity of the LRSPR sensor and the optimized design, the fabricated sensor achieves a temperature sensitivity of 3.6∼20.5 nm/°C, which is almost the highest among the optical fiber temperature sensors based on surface plasmon resonance reported experimentally. Moreover, the detection range of the proposed sensor can be easily tuned up to 170°C by varying the RI of the filled thermosensitive liquid, and the sensor performance remains stable. Considering that most temperature sensors using polydimethylsiloxane have a fixed detection range, this is an outstanding advantage that could expand the application field of the optical fiber temperature sensor.

Hollow-waveguide-based light-induced thermoelastic spectroscopy sensing.

In this Letter, a hollow waveguide (HWG)-based light-induced thermoelastic spectroscopy (LITES) gas sensing is proposed. An HWG with a length of 65 cm and inner diameter of 4 mm was used as the light transmission medium and gas chamber. The inner wall of the HWG was coated with a silver (Ag) film to improve reflectivity. Compared with the usually used multi-pass cell (MPC), the HWG has many advantages, such as small size, simple structure and fast filling. Compared with a hollow-core anti-resonant fiber (HC-ARF), the HWG has the merits of easy optical coupling, high system stability, and wide transmission range. A diode laser with output wavelength of 1.53 µm and a quantum cascade laser (QCL) with output wavelength of 4.58 µm were selected as the sources of excitation to target acetylene (C2H2) and carbon monoxide (CO), respectively, to verify the performance of the HWG-based LITES sensor in the near-infrared and mid-infrared regions. The experimental results showed that the HWG-based LITES sensor had a great linear responsiveness to the target gas concentration. The minimum detection limit (MDL) for C2H2 and CO was 6.07 ppm and 98.66 ppb, respectively.

Flexible Hollow Core Fiber Photoacoustic Gas Sensor Based on Embedded Acoustic Resonant Structure.

In this paper, we demonstrate a flexible leaky hollow core fiber (LHCF) photoacoustic (PA) gas sensor based on an embedded acoustic resonant structure. The sensor employs a part of a gas conduit as the buffer chamber to construct an equivalent T-type half-open PA cell. The LHCF is installed inside of the gas conduit and the LHCF is hence replaceable. Also, the flexibility of the LHCF and the gas conduit make the gas sensor flexible to reduce spatial size. The inner diameter and length of the LHCF are 1.6 mm and 70 mm, respectively. The inner diameter and length of the gas conduit are 4 mm and 210 mm, respectively. The total gas volume of the sensor is only ∼2.6 mL. Trace acetylene (C2H2) is selected as the target gas to evaluate the performance of the PA gas sensor. A near-infrared distributed feedback (DFB) laser is utilized to generate the PA signal, and an electrical micro-electro-mechanical system (MEMS) microphone is employed to extract the PA signal. The experimental results show that the minimum detection limit (MDL) can be as low as 21.1 ppb when the lock-in integration time is 200 s. And the normalized noise equivalent absorption coefficient (NNEA) is calculated to be 5.7 × 10-9·W/cm-1·Hz-1/2.

Highly sensitive photoacoustic gas sensor with micro-embedded acoustic resonator for gas leakage detection.

In this work, a photoacoustic (PA) gas sensor with a micro-embedded acoustic resonator for gas leakage detection was demonstrated. The micro-embedded acoustic resonator was fabricated by putting a leaky hollow-core fiber (L-HCF) into a cylindrical buffer chamber. The L-HCF was utilized as the PA cavity and the light transmission media simultaneously. The optimal inner diameter of the L-HCF was 1.7 mm. The embedded acoustic resonator was experimentally proven to be equivalent to a T-type half-open acoustic resonator, but the structure became much more compact. The volume of the amount of gas in the cell was only ∼0.3 mL, and the gas diffusion time to fill the sensor under room temperature (25°C) and ambient pressure (101 kPa) was ∼44 s. Trace acetylene (C2H2) in pure nitrogen (N2) was chosen as the target gas, and the minimum detectable limit (MDL) reached 29 ppb when the lock-in integration time was 1 s. The normalized noise equivalent absorption (NNEA) coefficient was calculated to be 3.0 × 10-9 W·cm-1·Hz-1/2. The micro-resonant PA gas sensor, with merits of compactness, low gas consumption, and low cost, has the potential to be a remote gas sensing scheme in fields of environmental protection, industrial process monitoring, and so on.

Low-frequency Resonant Photoacoustic Gas Sensor by Employing Hollow Core Fiber-Based O-Shaped Multipass Cells.

A low-frequency flexible resonant photoacoustic (PA) gas sensor using an O-shaped multipass cell is demonstrated. The PA sensor employed a flexible gradually tapered leaky hollow core fiber (LHCF). The LHCF was bent to be an end-to-end structure to make full use of the incident light. Additionally, the two ends of the LHCF were put inside a single buffer chamber, yielding an equivalent H-type acoustic resonator. The geometric size was reduced thanks to the bending structure. The geometric length of the LHCF was 500 mm. A micro-electro-mechanical-systems electrical microphone was installed at the center of the resonant tube to detect the PA signal. The proposed PA gas sensor exhibited a first-order longitudinal resonance frequency of 408 Hz. Trace acetylene (C2H2) was used as the target gas. The minimum detectable limit was calculated to be 25.8 parts-per-billion (ppb) with an average time of 400 s, which was 1.93 times higher than that of a single-pass PA gas sensor. The normalized noise-equivalent absorption coefficient and the PA cell constant were calculated to be 9.6 × 10-9 W·cm-1·Hz-1/2 and 8295 Pa/W·cm-1, respectively. The PA gas sensor owns a low resonance frequency and can be used for detection of most of the polar gaseous molecules, especially suitable for gas molecules with a long V-T relation time, such as carbon monoxide and carbon dioxide.

Potential Value of FAPI PET/CT in the Detection and Treatment of Fibrosing Mediastinitis: Preclinical and Pilot Clinical Investigation.

Fibrosing mediastinitis (FM) is a rare proliferative disease within the mediastinum that leads to pulmonary hypertension, which has been regarded as a major cause of death. This study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-PET/CT in the integration of diagnosis and treatment of FM through targeting FAPI in fibrosis rats and provide a theoretical basis for clinical management of FM patients. By performing a 18F-FAPI PET/CT scan, the presence of FAPI-avid in the fibrotic lesion was determined. Through a fibrosis rat model, 18F-FAPI-74 was used for lesion imaging and 177Lu-FAPI-46 was utilized to investigate the potential therapeutic effect on FM in vivo. In addition, biodistribution analysis and radiation dosimetry were carried out. With the 177Lu-FAPI-46 pharmacokinetic data of rats as the input, the estimated dose for female adults was computed, which can provide some useful information for the safe application of radiolabeled FAPI in the detection and treatment of FM in patients. Then, major findings on the use of FAPI PET/CT and SPECT/CT in FM were presented. 18F-FAPI-74 showed a high-level uptake in FM lesions of patients (SUVmax 7.94 ± 0.26), which was also observed in fibrosis rats (SUVmax 2.11 ± 0.23). Consistently, SPECT/CT imaging of fibrosis rats also revealed that 177Lu-FAPI-46-avid was active for up to 60 h in fibrotic lesions. In addition to this robust diagnostic performance, a possible therapeutic impact was evaluated as well. It turned out that no spontaneous healing of lesions was observed in the control group, whereas there was complete healing on day 9, day 11, and day 14 in the 30, 100, and 300 MBq groups, respectively. With a significant difference in the free of event rate in the Kaplan-Meier curve among four groups (P < 0.001), a dose of 300 MBq displayed the best therapeutic effect, and no obvious damage was observed in the kidney. Furthermore, organ-absorbed doses and an effective dose (0.4320 mSv/MBq) of 177Lu-FAPI-46 presumed for patients were assumed to give a preliminary indication of its safe use in clinical practice. In conclusion, 18F-FAPI-46 PET/CT can be a potentially valuable tool for the diagnosis of FM. Of note, 177Lu-FAPI-46 may be a novel and safe radiolabeled reagent for the integration of diagnosis and treatment of FM.

Dibazol-induced relaxation of ophthalmic artery in C57BL/6J mice is correlated with the potency to inhibit voltage-gated Ca2+ channels.

We aimed to explore the effect of dibazol on the ophthalmic artery (OA) and ophthalmic artery smooth muscle cells (OASMCs) of C57BL/6J mice as well as the underlying mechanisms. The OA of C57BL/6J mice was isolated under a dissecting microscope for primary OASMCs culture and myogenic tests. OASMCs were identified through morphological and immunofluorescence analyses. Morphology changes in the OASMCs were examined by staining using rhodamine-phalloidin. We performed a collagen gel contraction assay to measure the contractile and relaxant activities of the OASMCs. The molecular probe Fluo-4 AM was used to examine intracellular free Ca2+ levels ([Ca2+]in). The myogenic effects of OA were examined using wire myography. Additionally, the whole-cell patch-clamp technique was used to investigate the mechanisms underlying the relaxant effect of dibazol on L-type voltage-gated Ca2+ channels (LVGC) in isolated cells. 10-5 M dibazol significantly inhibited the contraction of OASMCs and increased the [Ca2+]in response to 30 mM KCl in a concentration-dependent manner. Dizabol had a more significant relaxant effect than 10-5 M isosorbide dinitrate (ISDN). Similarly, dibazol showed a significant dose-dependent relaxant effect on OA contraction induced by 60 mM KCl or 0.3 µM 9,11-Dideoxy-9α,11α-methanoepoxy prostaglandin F2α (U46619). The current-voltage (I-V) curve revealed that dibazol decreased Ca2+ currents in a concentration-dependent manner. In conclusion, dibazol exerted relaxant effects on the OA and OASMCs, which may involve the inhibition of the Ca2+ influx through LVGC in the cells.

An energy minimization strategy based on an improved nonlinear conjugate gradient method for accelerating the charged polymer dynamics simulation.

Using a hybrid simulation method that combines a non-linear conjugate gradient (NCG) method for solving large-scale unconstrained optimization problems with a Brownian dynamics (BD) model for polymer chains, we investigate the pre-equilibrium simulation of charged polymers in different dielectric systems from an energy minimization perspective. We propose an improved NCG coefficient (ßLPRPk) that satisfies a sufficient descent condition with a greater parameter under a strong Wolfe line search and converges globally for nonconvex minimization. Furthermore, preliminary numerical results show that the ßLPRPk coefficient is more efficient than many existing NCG coefficients for a large number of practical test problems from our model. We further compare the performance of the improved NCG method with that of other mainstream numerical methods in energy minimization, and the simulation results suggest that the NCG method is more competitive in terms of cost-effectiveness. Importantly, we apply the geometrically optimized configuration obtained by performing the NCG method to the pre-equilibrium simulation, and the numerical results show that it increases the computational efficiency of a pure solvent and biomolecule-solution systems at most by about 32 and 70 times, respectively, with the relative energy errors being controlled below 1 × 10-2 and 4.5 × 10-3, respectively. More importantly, the final pre-equilibrium configuration of the BD simulation that performs energy minimization and the traditional BD simulation matched closely.