Elucidation of the Molecular Mechanism of Compound Danshen Dripping Pills Against Angina Pectoris based on Network Pharmacology and Molecular Docking.

BACKGROUND: Compound Danshen dripping pills (CDDP), a traditional Chinese medicine, has had an extensive application in the treatment of angina pectoris (AP) in China. However, research on the bioactive ingredients and underlying mechanisms of CDDP in AP remains unclear. OBJECTIVE: In the present study, we explored the major chemical components and potential molecular mechanisms linked to the anti-angina effects of CDDP through the application of network pharmacology and molecular docking. METHODS: The potential targets of active ingredients in CDDP were sourced from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and the Swiss Target Prediction Database (STPD). Additionally, targets related to angina pectoris (AP) were retrieved from various databases, including Gene Cards, DisGeNET, Dis Genet, the Drug Bank database (DBD), and the Therapeutic Target Database (TDD). Protein- protein interaction [1] networks were also established, and core targets were identified based on their topological significance. GO enrichment analysis and KEGG pathway analysis were conducted using the R software. Interactions between active ingredients and potential targets selected through the above process were investigated through molecular docking. RESULTS: Seventy-six active ingredients were selected with the following criteria: OB ≥ 30%, DL ≥ 0.18. 383 targets of CDDP and 1488 targets on AP were gathered, respectively. Afterwards, 194 common targets of CDDP and anti-AP targets were defined, of which 12 were core targets. GO enrichment analysis indicated that CDDP acted on AP by response to lipopolysaccharide, regulating the reactive oxygen species and metal ion metabolism, and epithelial cell proliferation. In addition, KEGG enrichment analysis indicated that the signaling pathways were notably enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, IL-17 signaling pathway, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt signaling pathway, and TNF signaling pathway. Moreover, the molecular docking manifested excellent binding capacity between the active ingredients and targets on AP. CONCLUSION: This study comprehensively illustrated the bioactive, potential targets, and molecular mechanisms of CDDP against AP, offering fresh perspectives into the molecular mechanisms of CDDP in preventing and treating AP.

Identification of a novel m6A-related lncRNAs signature and immunotherapeutic drug sensitivity in pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) ranks as the fourth leading cause for cancer-related deaths worldwide. N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are closely related with poor prognosis and immunotherapeutic effect in PDAC. The aim of this study is to construct and validate a m6A-related lncRNAs signature and assess immunotherapeutic drug sensitivity in PDAC. METHODS: RNA-seq data for 178 cases of PDAC patients and 167 cases of normal pancreatic tissue were obtained from TCGA and GTEx databases, respectively. A set of 21 m6A-related genes were downloaded based on the previous report. Co-expression network was conducted to identify m6A-related lncRNAs in PDAC. Cox analyses and least absolute shrinkage and selection operator (Lasso) regression model were used to construct a risk prognosis model. The relationship between signature genes and immune function was explored by single-sample GSEA (ssGSEA). The tumor immune dysfunction and exclusion (TIDE) score and tumor mutation burden (TMB) were utilized to evaluate the response to immunotherapy. Furthermore, the expression levels of 4 m6A-related lncRNAs on PDAC cell lines were measured by the quantitative real-time PCR (qPCR). The drug sensitivity between the high- and low-risk groups was validated using PDAC cell lines by Cell-Counting Kit 8 (CCK8). RESULTS: The risk prognosis model was successfully constructed based on 4 m6A-related lncRNAs, and PDAC patients were divided into the high- and low-risk groups. The overall survival (OS) of the high-risk groups was more unfavorable compared with the low-risk groups. Receiver operating characteristic (ROC) curves demonstrated that the risk prognosis model reasonably predicted the 2-, 3- and 5-year OS of PDAC patients. qPCR analysis confirmed the decreased expression levels of 4 m6A-related lncRNAs in PDAC cells compared to the normal pancreatic cells. Furthermore, CCK8 assay revealed that Phenformin exhibited higher sensitivity in the high-risk groups, while Pyrimethamine exhibited higher sensitivity in the low-risk groups. CONCLUSION: The prognosis of patients with PDAC were well predicted in the risk prognosis model based on m6A-related lncRNAs, and selected immunotherapy drugs have potential values for the treatment of pancreatic cancer.

Liquid-Metal-Assisted Synthesis of Patterned GaN Thin Films for High-Performance UV Photodetectors Array.

GaN's outstanding physical characteristics allow for a wide range of applications in numerous industries. Although individual GaN-based ultraviolet (UV) photodetectors are the subject of in-depth research in recent decades, the demand for photodetectors array is rising as a result of advances in optoelectronic integration technology. However, as a prerequisite for constructing GaN-based photodetectors array, large-area, patterned synthesis of GaN thin films remains a certain challenge. This work presents a facile technique for pattern growing high-quality GaN thin films for the assembly of an array of high-performance UV photodetectors. This technique uses UV lithography, which is not only very compatible with common semiconductor manufacturing techniques, but also enables precise patterning modification. A typical detector has impressive photo-response performance under 365 nm irradiation, with an extremely low dark current of 40 pA, a high Ilight /Idark ratio over 105 , a high responsivity of 4.23 AW-1 , and a decent specific detectivity of 1.76 × 1012 Jones. Additional optoelectronic studies demonstrate the strong homogeneity and repeatability of the photodetectors array, enabling it to serve as a reliable UV image sensor with enough spatial resolution. These outcomes highlight the proposed patterning technique's enormous potential.

Nondual Antiplatelet Therapy Versus Dual Antiplatelet Therapy Before Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

ABSTRACT: Transcatheter aortic valve replacement (TAVR) is an interventional procedure performed in patients with severe aortic stenosis and often required perioperative antiplatelet therapy. Most previous studies have focused on antiplatelet therapy following TAVR. However, few studies have investigated the prognostic effect of preoperative antiplatelet therapy in patients undergoing TAVR. This study aimed to compare the efficacy and safety of nondual antiplatelet therapy (non-DAPT) and DAPT before TAVR. We performed a systematic search of Embase, PubMed, and Web of Science until February 2023. Studies were eligible if they compared non-DAPT (single antiplatelet therapy or no antiplatelet therapy) with DAPT in patients before TAVR. A total of 5 studies, including 2329 patients, met the inclusion criteria and were included in the meta-analysis. Preoperative non-DAPT significantly decreased minor bleeding events compared with preoperative DAPT [odds ratio 0.58; 95% confidence interval: 0.44-0.76]. There were no significant differences in the incidence of other bleeding events, transfusions, stroke, myocardial infarction, or all-cause death. Preoperative single antiplatelet therapy significantly decreased the incidence of major bleeding compared with DAPT (odds ratio 0.14; 95% confidence interval: 0.04-0.48). Preoperative non-DAPT significantly reduced minor bleeding events in patients undergoing TAVR, without increasing the risk of stroke and myocardial infarction.

First insights into 6PPD-quinone formation from 6PPD photodegradation in water environment.

p-Phenylenediamines (PPDs), an important type of rubber antioxidants, have received little study on their environmental fate, particularly for their vital photodegradation process in water environment. Accordingly, N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (6PPD), as a representative of PPDs, was investigated experimentally and theoretically for its photodegradation in water. Rapid photodegradation occurred when 6PPD was exposed to illumination especially UV region irradiation. Under acidic conditions, the photodegradation of 6PPD accelerated mainly due to the increased absorption of long wavelength irradiation by ionized 6PPD. Nine photodegradation products (e.g., 6PPD-quinone (6PPDQ)) of 6PPD were identified by an ultra-performance liquid chromatography QTOF mass spectrometry. Molar yields of photoproducts such as 6PPDQ, aniline, 4-aminodiphenylamine, and 4-hydroxydiphenylamine were 0.03 ± 0.00, 0.10 ± 0.01, 0.03 ± 0.02, and 0.08 ± 0.01, respectively. Mechanisms involved in 6PPD photodegradation include photoexcitation, direct photolysis, self-sensitized photodegradation, and 1O2 oxidation, as demonstrated by electron paramagnetic resonance (EPR) analysis, scavenging experiments, and the time-dependent density functional theory (TD-DFT). Notably, the toxicity of the reaction solution formed during the photodegradation of 6PPD was increased by the formation of highly toxic products (e.g., 6PPDQ). This study provides the first explanation for photodegradation mechanisms of 6PPD and confirms the pathway of 6PPDQ produced by the photoreaction in water environment.

Comprehensive analysis of disulfidptosis-related lncRNA features for prognosis and immune landscape prediction in colorectal cancer.

Disulfidptosis is a novel mechanism underlying actin-cytoskeleton-associated cell death, but its function in colorectal cancer (CRC) is still elusive. In this study, we investigated the potential role of Disulfidptosis-Related Long Non-Coding RNAs (DRLs) as prognostic indicators in CRC. Through transcriptome data from TCGA CRC cases, we identified 44 prognosis-correlated DRLs by Univariate Cox Regression Analysis and observed a differential expression pattern of these DRLs between CRC and normal tissues. Consensus clustering analysis based on DRL expression led to subgroup classification of CRC patients with distinct molecular fingerprints, accompanied by a superior survival outcome in cluster 2. We are encouraged to develop a score model incorporating 12 key DRLs to predict patient outcomes. Notably, this model displayed more reliable accuracy than other predictive indicators since DRLs are intimately related to tumor immune cell infiltration, suggesting a considerable potential of our DRL-score model for tumor therapy. Our data offered a valuable insight into the prognostic significance of DRLs in CRC and broke a new avenue for tumor prognosis prediction.

Liquid-metal based flexible a-IZTO ultrathin films for electrical and optical applications.

Amorphous indium zinc tin oxide (a-IZTO) is a kind of transparent conductive oxide (TCO), which can be used in transparent electrodes, transistors, and flexible devices. At present, a key limitation of a-IZTO is the costly vacuum manufacturing technology, and its commercial production is also restricted by the complex raw material preparation process. In this article, we report a liquid metal-based van der Waals (vdW) exfoliation technique by which a-IZTO films with several nanometres thickness are fabricated. The a-IZTO films fabricated in ambient air have a size on the centimeter scale and an optical transmittance of 99.64%; they are also large-area flexible oxide films. In order to illustrate the capabilities of this technology, we fabricated thin film transistors (TFTs) and photodetectors based on a-IZTO films. An a-IZTO thin film transistor (TFT) has an on/off ratio of 106. When the Vds is 5 V, the responsivity, detectivity and external quantum efficiency of an a-IZTO photodetector are 7.57 × 104 A W-1, 4.00 × 1015 Jones and 3.68 × 105%, respectively, exhibiting one of the top performances in this field.

Type-I PtS2/MoS2 van der Waals heterojunctions with tunable photovoltaic effects and high photosensitivity.

Recent advances in two-dimensional (2D) materials play an essential role in boosting modern electronics and optoelectronics. Thus far, transition metal dichalcogenides (TMDs) as emerging members of 2D materials, and the van der Waals heterostructures (vdWHs) based on TMDs have been extensively investigated owing to their prominent capabilities and unique crystal structures. In this work, an original vdWH composed of molybdenum disulfide (MoS2) and platinum disulfide (PtS2) was comprehensively studied as a field-effect transistor (FET) and photodetector. A gate-tunable rectifying behavior was obtained, stemming from the band design of PtS2/MoS2 vdWH. Upon 685 nm laser illumination, it also exhibited a superior photodetection performance with a distinctly high photoresponsivity of 403 A W-1, a comparable detectivity of 1.07 × 1011 Jones, and an excellent external quantum efficiency of 7.32 × 104%. More importantly, fast rise (24 ms) and decay (21 ms) times were obtained under 685 nm light illumination attributed to the unilateral depletion region structure. Further, the photovoltaic effect and photocurrent of the heterojunction could be modulated by a back gate voltage. All these results indicated that such 2D-TMD-based vdWHs provide a new idea for realizing high-performance electronic and optoelectronic devices.

Abnormal linear dichroism transition in two-dimensional PdPS.

The linear dichroism (LD) conversion shows promising applications for polarized detectors, optical transition and light propagation. However, polarity reversal always occurs at a certain wavelength in LD materials, which can only distinguish two wavelength bands as wavelength-selective photodetectors. In this study, the multi-degree-of-freedom of optical anisotropy based on 2D PdPS flakes is carefully described, in which four critical switching wavelengths are observed. Remarkably, the quadruple LD conversion shows a significant wavelength-dependent behavior, allowing us to pinpoint five wavelength bands, 200-239 nm, 239-259 nm, 259-469 nm, 469-546 nm, and 546-700 nm, for a wavelength-selective approach to photodetectors. In addition, the polarized photoresponse under 532 nm was realized with an anisotropy factor of ∼1.51 and further illustrated the in-plane anisotropy. Raman spectroscopy of PdPS flakes also shows strong phonon anisotropy. The unique wavelength-selective property shows great potential for the miniaturization and integration of photodetectors.

Type-I Heterostructure Based on WS2/PtS2 for High-Performance Photodetectors.

van der Waals (vdW) heterodiodes composed of two-dimensional (2D) layered materials led to a new prospect in photoelectron diodes and photovoltaic devices. Existing studies have shown that Type-I heterostructures have great potential to be used as photodetectors; however, the tunneling phenomena in Type-I heterostructures have not been fully revealed. Herein, a highly efficient nn+ WS2/PtS2 Type-I vdW heterostructure photodiode is constructed. The device shows an ultrahigh reverse rectification ratio of 105 owing to the transmission barrier-induced low reverse current. A unilateral depletion region is formed on WS2, which inhibits the recombination of carriers at the interface and makes the external quantum efficiency (EQE) of the device reach 67%. Due to the tunneling mechanism of the device, which allows the co-existence of a large photocurrent and a low dark current, this device achieves a light on/off ratio of over 105. In addition, this band design allows the device to maintain a high detectivity of 4.53 × 1010 Jones. Our work provides some new ideas for exploring new high-efficiency photodiodes.

A Submicrosecond-Response Ultraviolet-Visible-Near-Infrared Broadband Photodetector Based on 2D Tellurosilicate InSiTe3.

2D material (2DM) based photodetectors with broadband photoresponse are of great value for a vast number of applications such as multiwavelength photodetection, imaging, and night vision. However, compared with traditional photodetectors based on bulk material, the relatively slow speed performance of 2DM based photodetectors hinders their practical applications. Herein, a submicrosecond-response photodetector based on ternary telluride InSiTe3 with trigonal symmetry and layered structure was demonstrated in this study. The InSiTe3 based photodetectors exhibit an ultrafast photoresponse (545-576 ns) and broadband detection capabilities from the ultraviolet (UV) to the near-infrared (NIR) optical communication region (365-1310 nm). Besides, the photodetector presents an outstanding reversible and stable photoresponse in which the response performance remains consistent within 200 000 cycles of switch operation. These significant findings suggest that InSiTe3 can be a promising candidate for constructing fast response broadband 2DM based optoelectronic devices.

Molecularly-imprinted hydrogel beads via self-sacrificing micro-reactors as safe and selective bilirubin adsorbents.

For patients who are suffering from liver dysfunction or metabolic obstruction, excessive bilirubin (BIL) in their bodies may cause jaundice with irreversible cerebral injury. Traditional exchange transfusion and photodynamic therapy pose a risk of serious adverse reactions or limited curative effects. Therefore, as a generally used treatment, hemoperfusion (HP) purifies patients' blood with solid adsorbents. However, the development of clinical BIL absorbents is greatly impeded by low selectivity and unsatisfactory blood compatibility. Herein, inspired by oviparity, we propose BIL-imprinted poly(acrylic acid-co-sodium p-styrenesulfonate)-reduced graphene oxide (PAA-SS-rGO@BIL) hydrogel beads as BIL adsorbents via self-sacrificing micro-reactors. In the micro-reactors, cross-linked polymerization is achieved and a solidified gel is formed. The received hydrogel beads show outstanding selective adsorption capabilities toward BIL due to the recognition sites, and π-π and hydrophobic interactions. Such hydrogel beads possess superior blood compatibility owing to their bioinspired heparin-mimicking gel structure. Simulated BIL selective adsorption experiments in vitro demonstrate that the BIL concentrations in the plasma of a patient with severe jaundice can be restored to a moderate level within 3 hours. Therefore, hydrogel beads offer new options for clinical BIL adsorption.

Broken-Gap PtS2/WSe2 van der Waals Heterojunction with Ultrahigh Reverse Rectification and Fast Photoresponse.

Broken-gap van der Waals (vdW) heterojunctions based on 2D materials are promising structures to fabricate high-speed switching and low-power multifunctional devices thanks to its charge transport versus quantum tunneling mechanism. However, the tunneling current is usually generated under both positive and negative bias voltage, resulting in small rectification and photocurrent on/off ratio. In this paper, we report a broken-gap vdW heterojunction PtS2/WSe2 with a bilateral accumulation region design and a big band offset by utilizing thick PtS2 as an effective carrier-selective contact, which exhibits an ultrahigh reverser rectification ratio approaching 108 and on/off ratio over 108 at room temperature. We also find excellent photodetection properties in such a heterodiode with a large photocurrent on/off ratio over 105 due to its ultralow forward current and a comparable photodetectivity of 3.8 × 1010 Jones. In addition, the response time of such a photodetector reaches 8 µs owing to the photoinduced tunneling mechanism and reduced interface trapping effect. The proposed heterojunction not only demonstrates the high-performance broken-gap heterodiode but also provides in-depth understanding of the tunneling mechanism in the development of future electronic and optoelectronic applications.

2D Silicon-Based Semiconductor Si2 Te3 toward Broadband Photodetection.

Silicon-based semiconductor materials dominate modern technology for more than half a century with extraordinary electrical-optical performance and mutual processing compatibility. Now, 2D materials have rapidly established themselves as prospective candidates for the next-generation semiconductor industry because of their novel properties. Considering chemical and processing compatibility, silicon-based 2D materials possess significant advantages in integrating with silicon. Here, a systematic study is reported on the structural, electrical, and optical performance of silicon telluride (Si2 Te3 ) 2D material, a IV-VI silicon-based semiconductor with a layered structure. The ultrawide photoluminescence (PL) spectra in the range of 550-1050 nm reveals the intrinsic defects in Si2 Te3 . The Si2 Te3 -based field-effect transistors (FETs) and photodetectors show a typical p-type behavior and a remarkable broadband spectral response in the range of 405-1064 nm. Notably, the photoresponsivity and detectivity of the photodetector device with 13.5 nm in thickness and upon 405 nm illumination can reach up to 65 A W-1 and 2.81 × 1012 Jones, respectively, outperforming many traditional broadband photodetectors. It is believed this work will excite interests in further exploring the practical application of 2D silicon-based materials in the field of optoelectronics.

Metal-Organic Framework/Ag-Based Hybrid Nanoagents for Rapid and Synergistic Bacterial Eradication.

Recent emerged metal-organic frameworks (MOFs), as superior drug carriers, provide novel strategies to combat pathogenic bacterial infections. Although various antibacterial metal ions can be easily introduced in MOFs for chemical bacterial ablation, such a single-model bactericidal method suffers from high-dose use, limited antibacterial efficiency, and slow sterilization rate. Hence, developing a dual bactericidal system is urgently required. Herein, we report an MOF/Ag-derived nanocomposite with efficient metal-ion-releasing capability and robust photo-to-thermal conversion effect for synergistic sterilization. The MOF-derived nanocarbon consisting of metallic zinc and a graphitic-like carbon framework is first synthesized, and then Ag nanoparticles (AgNPs) are evenly introduced via the displacement reaction between Zn and Ag+. Upon near-infrared irradiation, the fabricated nanoagents can generate massive heat to destroy bacterial membranes. Meanwhile, abundant Zn2+ and Ag+ ions are released to make chemical damage to bacterial intracellular substances. Systematic antibacterial experiments reveal that such dual-antibacterial effort can endow the nanoagents with nearly 100% bactericidal ratio for highly concentrated bacteria at a very low dosage (0.16 mg/mL). Furthermore, the nanoagents exhibit less cytotoxicity, which provides potential possibilities for the applications in the biological field. In vivo assessment indicates that the nanocomposites can realize rapid and safe wound sterilization and are expected to be an alternative to antibiotics. Overall, we present an easily fabricated structure-engineered nanocomposite with chemical and photothermal effects for broad-spectrum bacterial sterilization.

Construction of Kevlar nanofiber/graphene oxide composite beads as safe, self-anticoagulant, and highly efficient hemoperfusion adsorbents.

Recently emerged hemoperfusion absorbents, e.g. ion-exchange resin, activated carbon, and other porous materials, provide numerous novel possibilities to cure chronic liver failure (CLF) and renal failure (CRF). However, the limited adsorption performance and unsatisfactory blood compatibility significantly impede the development of the absorbents. Hence, designing safe and self-anticoagulant hemoperfusion absorbents with robust toxin clearance remains a considerable challenge. Here, brand new Kevlar-based composite gel beads for hemoperfusion are prepared by interface assembly based on π-π interaction. First, Kevlar nanofiber-graphene oxide (K-GO) beads are produced by liquid-liquid phase separation. Then, sodium p-styrenesulfonate (SS) is adsorbed onto the K-GO interface by π-π interaction and initiated to achieve the composite gel (K-GO/PSS) beads with an interfacial crosslinked structure. Such composite gel beads possess superior mechanical strength and self-anticoagulation capability, owing to the dual-network structure and heparin-mimicking gel structure, respectively. Furthermore, the K-GO/PSS beads show robust adsorption capacities for different kinds of toxins due to their strong charge and π-π interactions. A simulated hemoperfusion experiment in vitro demonstrates that the concentrations of the toxins in the blood can be restored to normal values within 30 minutes. In general, we envision that such composite gel beads will provide new strategies for future clinical CLF and CRF treatments.

Prevalence of comorbidities in chronic obstructive pulmonary disease patients: A meta-analysis.

BACKGROUND: This study compares the prevalence rates of comorbidities between chronic obstructive pulmonary disease (COPD) and non-COPD control patients reported in literature. METHOD: Literature was searched in several electronic databases. After the selection of studies by following précised eligibility criteria, meta-analyses of odds ratios (ORs) were carried out with subgroup and sensitivity analyses under random effects model. RESULTS: Eleven studies (47,695,183 COPD and 47,924,876 non-COPD control patients' data) were used for meta-analysis. Average age of COPD patients was 66.66 ±â€Š8.72 years of whom 55.4 ±â€Š11.9% were males. The prevalence of cardiovascular comorbidities [OR 1.90, 95% confidence interval (95% CI) 1.59-2.28; P < .00001], cerebrovascular comorbidities (OR 1.84, 95% CI 1.47-2.31; P < .00001), hypertension (OR 1.45, 95% CI 1.31-1.61; P < .00001), diabetes mellitus (OR 1.22, 95% CI 1.07-1.38; P = .003), neurological and psychiatric disorders (OR 1.78, 95% CI 1.48-2.14; P < .00001), gut and renal disorders (OR 1.96, 95% CI 1.43-2.68; P < .00001), musculoskeletal disorders (OR 1.51, 95% CI 1.27-1.78; P < .00001), non-COPD respiratory comorbidities (OR 2.81, 95% CI 2.52-3.14; P < .00001), and cancer (OR 1.67, 95% CI 1.25-2.23; P = .0005) were significantly higher in COPD patients than in non-COPD controls. CONCLUSION: COPD is associated with significantly higher comorbidities than in other diseases that should be taken into consideration in COPD control strategies.