Design Principles for Smart Linear Polymer Ligand Carriers with Efficient Transcellular Transport Capabilities.

The surface functionalization of polymer-mediated drug/gene delivery holds immense potential for disease therapy. However, the design principles underlying the surface functionalization of polymers remain elusive. In this study, we employed computer simulations to demonstrate how the stiffness, length, density, and distribution of polymer ligands influence their penetration ability across the cell membrane. Our simulations revealed that the stiffness of polymer ligands affects their ability to transport cargo across the membrane. Increasing the stiffness of polymer ligands can promote their delivery across the membrane, particularly for larger cargoes. Furthermore, appropriately increasing the length of polymer ligands can be more conducive to assisting cargo to enter the lower layer of the membrane. Additionally, the distribution of polymer ligands on the surface of the cargo also plays a crucial role in its transport. Specifically, the one-fourth mode and stripy mode distributions of polymer ligands exhibited higher penetration ability, assisting cargoes in penetrating the membrane. These findings provide biomimetic inspiration for designing high-efficiency functionalization polymer ligands for drug/gene delivery.

Selective Cleavage of Cß-O-4 Bond for Lignin Depolymerization via Paired-Electrolysis in an Undivided Cell.

The cleavage of C-O bonds is one of the most promising strategies for lignin-to-chemicals conversion, which has attracted considerable attention in recent years. However, current catalytic system capable of selectively breaking C-O bonds in lignin often requires a precious metal catalyst and/or harsh conditions such as high-pressure H2 and elevated temperatures. Herein, we report a novel protocol of paired electrolysis to effectively cleave the Cß-O-4 bond of lignin model compounds and real lignin at room temperature and ambient pressure. For the first time, "cathodic hydrogenolysis of Cß-O-4 linkage" and "anodic C-H/N-H cross-coupling reaction" are paired in an undivided cell, thus the cleavage of C-O bonds and the synthesis of valuable triarylamine derivatives could be simultaneously achieved in an energy-effective manner. This protocol features mild reaction conditions, high atom economy, remarkable yield with excellent chemoselectivity, and feasibility for large-scale synthesis. Mechanistic studies indicate that indirect H* (chemical absorbed hydrogen) reduction instead of direct electron transfer might be the pathway for the cathodic hydrogenolysis of Cß-O-4 linkage.

Scalable and Selective Electrochemical Hydrogenation of Polycyclic Arenes.

The reduction of aromatic compounds constitutes a fundamental and ongoing area of investigation. The selective reduction of polycyclic aromatic compounds to give either fully or partially reduced products remains a challenge, especially in applications to complex molecules at scale. Herein, we present a selective electrochemical hydrogenation of polycyclic arenes conducted under mild conditions. A noteworthy achievement of this approach is the ability to finely control both the complete and partial reduction of specific aromatic rings within polycyclic arenes by judiciously varying the reaction solvents. Mechanistic investigations elucidate the pivotal role played by in situ proton generation and interface regulation in governing reaction selectivity. The reductive electrochemical conditions show a very high level of functional-group tolerance. Furthermore, this methodology represents an easily scalable reduction (demonstrated by the reduction of 1 kg scale starting material) using electrochemical flow chemistry to give key intermediates for the synthesis of specific drugs.

Fast fringe projection profilometry using 3 + 1 phase retrieval strategy and fringe order correction.

Fringe projection profilometry (FPP) has attracted wide attention in optical 3D measurement field for its high resolution, high accuracy, and simple system construction. However, the inherent requirements of FPP's measurement speed and accuracy are contradictory. We adopt a 3+1 phase retrieval strategy combining phase shift and the Hilbert transform algorithm to achieve high-speed, high-precision simultaneous measurements with only four binary fringe patterns. Furthermore, when using temporal phase unwrapping, fringe order errors (FOEs) are inevitable. Although these FOEs do not affect neighboring pixels, they are brought into the final point cloud coordinates by the absolute phase value. We propose a fringe order correction method to eliminate FOEs. The feasibility and effectiveness of this method are verified by the experimental results.

Radiomics analysis of pericoronary adipose tissue based on plain CT for preliminary screening of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a markedly increased prevalence of coronary artery disease (CAD). Radiomics features of pericoronary adipose tissue (PCAT) were correlated with inflammation, which may have potential value in the prediction of CAD. PURPOSE: To determine whether radiomics analysis of PCAT captured by plain computed tomography (CT) could predict obstructive CAD in patients with T2DM. MATERIAL AND METHODS: The study included 155 patients with T2DM with suspected CAD between January 2020 and December 2021. Volumes of right coronary artery of 10-50 mm were delineated in the plain CT to extract radiomics features and PCAT CT attenuation (PCATa). Least absolute shrinkage and selection operator was used to select the useful radiomics features to calculate the radiomics score (Rad-score). Univariate and multivariable logistic regression were applied to select independent predictors. The predictive performance was evaluated by the area under the receiver operating characteristics curve (AUC). RESULTS: Rad-score (per 0.1 increments: odds ratio [OR] = 1.297; P < 0.001), coronary artery calcium score (CACS) (OR = 1.003; P = 0.037), and sex (OR = 3.245; P = 0.026) were identified as independent predictors for obstructive CAD. Rad-score (AUC = 0.835) outperformed CACS (AUC = 0.780), sex (AUC = 0.665), and PCATa (AUC = 0.550) in predicting obstructive CAD (P = 0.017 and 0.003 for Rad-score vs. sex and PCATa, respectively); however, the improvement between Rad-score and CACS had no statistical significance (P = 0.490). CONCLUSION: Plain CT-derived Rad-score may be used as a preliminary screening tool for obstructive CAD in patients with T2DM.

Persistent Uptake of H2O2 onto Ambient PM2.5 via Dark-Fenton Chemistry.

Particulate matter (PM) and gaseous hydrogen peroxide (H2O2) interact ubiquitously to influence atmospheric oxidizing capacity. However, quantitative information on H2O2 loss and its fate on urban aerosols remain unclear. This study investigated the kinetics of heterogeneous reactions of H2O2 on PM2.5 and explored how these processes are affected by various experimental conditions (i.e., relative humidity, temperature, and H2O2 concentration). We observed a persistent uptake of H2O2 by PM2.5 (with the uptake coefficients (γ) of 10-4-10-3) exacerbated by aerosol liquid water and temperature, confirming the critical role of water-assisted chemical decomposition during the uptake process. A positive correlation between the γ values and the ratio of dissolved iron concentration to H2O2 concentration suggests that Fenton catalytic decomposition may be an important pathway for H2O2 conversion on PM2.5 under dark conditions. Furthermore, on the basis of kinetic data gained, the parameterization of H2O2 uptake on PM2.5 was developed and was applied into a box model. The good agreement between simulated and measured H2O2 uncovered the significant role that heterogeneous uptake plays in the sink of H2O2 in the atmosphere. These findings suggest that the composition-dependent particle reactivity toward H2O2 should be considered in atmospheric models for elucidating the environmental and health effects of H2O2 uptake by ambient aerosols.

Electrochemical Palladium-Catalyzed Oxidative Sonogashira Carbonylation of Arylhydrazines and Alkynes to Ynones.

Oxidative carbonylation using carbon monoxide has evolved as an attractive tool to valuable carbonyl-containing compounds, while mixing CO with a stoichiometric amount of a chemical oxidant especially oxygen is hazardous and limits its application in scale-up synthesis. By employing anodic oxidation, we developed an electrochemical palladium-catalyzed oxidative carbonylation of arylhydrazines with alkynes, which is regarded as an alternative supplement of the carbonylative Sonogashira reaction. Combining an undivided cell with constant current mode, oxygen-free conditions avoids the explosion hazard of CO. A diversity of ynones are efficiently obtained using accessible arylhydrazines and alkynes under copper-free conditions. A possible mechanism of the electrochemical Pd(0)/Pd(II) cycle is rationalized based upon cyclic voltammetry, kinetic studies, and intermediates experiments.

Correlation of serum delta-like ligand-4 level with the severity of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is one of the most serious microvascular complications of type 2 diabetes mellitus (T2DM). Delta-like ligand-4 (DLL4) maintains the normal physiological microenvironment of the retina. However, the relationship between the level of DLL4 and the severity of DR remains unclear. METHODS: We retrospectively analyzed serum DLL4 levels and other laboratory and clinical data in 94 T2DM patients (35 patients without DR [NDR], 32 with non-proliferative DR [NPDR], 27 with proliferative DR [PDR]), and 30 healthy controls. RESULTS: The serum DLL4 level was significantly greater in the NDR group (43.38 ± 16.23 pg/mL), NPDR group (56.57 ± 25.89 pg/mL), and PDR group (74.97 ± 25.28 pg/mL) than in the healthy controls (29.9 ± 8.92 pg/mL; all p < 0.05). Among T2DM patients, the level of DLL4 increased as the severity of DR increased (p < 0.05). Logistic regression analysis demonstrated that DR was positively associated with DLL4, glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), and duration of T2DM (all p < 0.05). Consistently, receiver operating characteristic (ROC) curve analysis also indicated that DLL4 was a potential candidate biomarker for identifying the severity of DR. CONCLUSIONS: T2DM patients, especially those with DR, have increased serum levels of DLL4. DLL4 may be used as a biomarker and an independent risk factor for DR, and targeting DLL4 may be a potential therapy in patients with DR.

Defocused binary fringe phase error modeling and compensation using depth-discrete Fourier series fitting.

The binary defocus fringe projection is a widely adopted way to increase the speed of fringe projection profilemotry. However, the projected patterns may deviate from ideal ones at some depths. We propose a theoretical model and a corresponding compensation method to explain and calibrate the phase error of defocus-projected patterns. We first low-pass filter the projected patterns at different depths to obtain corresponding ideal ones. Then, we calibrate the model coefficients based on the errors between the original and ideal fringe patterns. The calibrated phase error model can be used to compensate the phase error at arbitrary depths within the calibration volume. Experiments are conducted to verify the feasibility and performance of the proposed method.

Deep learning-based coronary artery calcium score to predict coronary artery disease in type 2 diabetes mellitus.

Background: Coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients often presents diffuse lesions, with extensive calcification, and it is time-consuming to measure coronary artery calcium score (CACS). Objectives: To explore the predictive ability of deep learning (DL)-based CACS for obstructive CAD and hemodynamically significant CAD in T2DM. Methods: 469 T2DM patients suspected of CAD who accepted CACS scan and coronary CT angiography between January 2013 and December 2020 were enrolled. Obstructive CAD was defined as diameter stenosis ≥50%. Hemodynamically significant CAD was defined as CT-derived fractional flow reserve ≤0.8. CACS was calculated with a fully automated method based on DL algorithm. Logistic regression was applied to determine the independent predictors. The predictive performance was evaluated with area under receiver operating characteristic curve (AUC). Results: DL-CACS (adjusted odds ratio (OR): 1.005; 95% CI: 1.003-1.006; P ＜ 0.001) was significantly associated with obstructive CAD. DL-CACS (adjusted OR:1.003; 95% CI: 1.002-1.004; P ＜ 0.001) was also an independent predictor for hemodynamically significant CAD. The AUCs, sensitivities, specificities, positive predictive values and negative predictive values of DL-CACS for obstructive CAD and hemodynamically significant CAD were 0.753 (95% CI: 0.712-0.792), 75.9%, 66.5%, 74.8%, 67.8% and 0.769 (95% CI: 0.728-0.806), 80.7%, 62.1%, 59.6% and 82.3% respectively. It took 1.17 min to perform automated measurement of DL-CACS in total, which was significantly less than manual measurement of 1.73 min (P ＜ 0.001). Conclusions: DL-CACS, with less time-consuming, can accurately and effectively predict obstructive CAD and hemodynamically significant CAD in T2DM.

Hydrolysis reactivity reveals significant seasonal variation in the composition of organic peroxides in ambient PM2.5.

Atmospheric organic peroxides (POs) play a key role in the formation of O3 and secondary organic aerosol (SOA), impacting both air quality and human health. However, there still remain technical challenges in investigating the reactivity of POs in ambient aerosols due to the instability and lack of standards for POs, impeding accurate evaluation of their environmental impacts. In the present study, we conducted the first attempt to categorize and quantify POs in ambient PM2.5 through hydrolysis, which is an important transformation pathway for POs, thus revealing the reactivities of various POs. POs were generally categorized into hydrolyzable POs (HPO) and unhydrolyzable POs (UPO). HPO were further categorized into three groups: short-lifetime HPO (S-HPO), intermediate-lifetime HPO (I-HPO), and long-lifetime HPO (L-HPO). S-HPO and L-HPO are typically formed from Criegee intermediate (CI) and RO2 radical reactions, respectively. Results show that L-HPO are the most abundant HPO, indicating the dominant role of RO2 pathway in HPO formation. Despite their lower concentration compared to L-HPO, S-HPO make a major contribution to the HPO hydrolysis rate due to their faster rate constants. The hydrolysis of PM2.5 POs accounts for 19 % of the nighttime gas-phase H2O2 growth during the summer observation, constituting a noteworthy source of gas-phase H2O2 and contributing to the atmospheric oxidation capacity. Seasonal and weather conditions significantly impact the composition of POs, with HPO concentrations in summer being significantly higher than those in winter and elevated under rainy and nighttime conditions. POs are mainly composed of HPO in summer, while in winter, POs are dominated by UPO.

The application value of 24†h Holter monitoring indices in predicting MACEs outside the hospital within three years after PCI in patients with STEMI.

Background: Evaluating cardiovascular risk in patients experiencing acute ST-elevation myocardial infarction (STEMI) and undergoing percutaneous coronary intervention (PCI) is crucial for early intervention and improving long-term outcomes. 24 h Holter monitoring provides continuous cardiac electrophysiological data, enabling the detection of arrhythmias and autonomic dysfunction that are not captured during routine examinations. This study aimed to examine the relationship between Holter monitoring metrics and the occurrence of out-of-hospital major adverse cardiovascular events (MACEs) following PCI in patients with STEMI, offering insights into cardiovascular risk evaluation. Methods: This prospective cohort study included STEMI patients undergoing PCI. 24 h Holter monitoring data were recorded, including heart rate, heart rate variability (HRV) metrics such as SDNN and SDANN index, heart rate deceleration capacity (DC) at different time scales (DC2, DC4, DC8), and the frequency of premature ventricular contractions (PVCs). Independent correlations between these indices and MACEs, as well as cardiovascular deaths, were investigated using multifactorial logistic regression. Predictive capacities were assessed through receiver operating characteristic (ROC) curves. Results: A total of 172 participants were enrolled in this study. Over the 3-year follow-up period, MACEs were observed in 57 patients, including 20 cases of cardiac death. In logistic regression models adjusted for confounding variables, SDNN [OR: 0.980; 95% CI: (0.967, 0.994); p = 0.005] and SDANN index [OR: 0.982; 95% CI: (0.969, 0.996); p = 0.009] were negatively associated with the incidence of MACEs. Conversely, the slowest heart rate [OR: 1.075; 95% CI: (1.022, 1.131); p = 0.005] and frequent PVCs [OR: 2.685; 95% CI: (1.204, 5.987); p = 0.016] demonstrated a positive association with MACEs. Furthermore, SDNN [OR: 0.957; 95% CI: (0.933, 0.981); p = 0.001], DC [OR: 0. 702; 95% CI: (0.526, 0.938); p = 0.017]) and DC4 [OR: 0.020; 95% CI: (0.001, 0.664); p = 0.029] were negatively associated with cardiac death. The ROC analysis results indicated that SDNN was an effective predictor of both MACEs [AUC: 0.688 (95% CI: 0.601-0.776)] and cardiac death [AUC: 0.752 (95% CI: 0.625-0.879)]. Conclusion: HRV, DC metrics, and frequent PVCs obtained by 24 h Holter monitoring were associated with the risk of MACEs in STEMI patients. These metrics can help clinicians identify at-risk patients early so that timely interventions.

Clinical significance of tumor abnormal protein in patients with type 2 diabetes complicated with lung adenocarcinoma in situ.

BACKGROUND: To investigate the application value of tumor abnormal protein in patients with type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. MATERIALS AND METHODS: A total of 140 patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ (Group A), 160 patients with type 2 diabetes mellitus (Group B), and 120 healthy controls (Group C) were enrolled in the Department of Thoracic Surgery of the First Affiliated Hospital of Soochow University from November 2021 to December 2022. RESULTS: The total cholesterol level was higher in Group A than in Group B (p < 0.05) and Group C (p < 0.01), and it was higher in Group B than in Group C (p < 0.01). The comparison results of cholesterol level were similar to those of tumor abnormal protein, low-density lipoprotein cholesterol, and glycosylated hemoglobin among the three groups. The triglyceride level was higher in Group A than in Group B and Group C (both p < 0.01). Group A had a higher level of high-density lipoprotein cholesterol than Group C (p < 0.01). The fasting plasma glucose level was higher in Group A than in Group B and Group C (both, p < 0.01). These findings indicated that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. CONCLUSION: Therefore, detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

The study found that tumor abnormal protein, glycosylated hemoglobin, high-density lipoprotein cholesterol, and fasting plasma glucose were independent factors for patients having type 2 diabetes mellitus complicated with lung adenocarcinoma in situ. Detecting tumor abnormal protein levels may help diagnose lung adenocarcinoma in situ in patients with type 2 diabetes mellitus.

Clinical Significance of Thrombelastography Results in Patients with Lung Adenocarcinoma in Situ Complicated with Type 2 Diabetes.

To investigate the significance of thrombelastography (TEG) in patients who have lung adenocarcinoma in situ (LAIS) complicated with type 2 diabetes (T2D), 120 subjects were enrolled: 40 with LAIS, 40 with LAIS and T2D (LAIS + T2D), and 40 healthy controls (HCs). Correlation analysis was used to assess the relationships of TEG with indicators of T2D. The LAIS + T2D group had lower reaction time (R), rate of clot formation (K), estimated percentage of lysis (EPL), and lysis after 30 min (LY30), but higher maximum amplitude (MA), angle (α), and coagulation index (CI) than other group. Compared with the HC group, the LAIS group had lower R, K, EPL, and LY30, but higher MA, α, and CI. In LAIS + T2D group, R and LY30 had negatively correlations with fasting blood glucose (FBG) and triglycerides (TGs); α and MA had positive correlations with FBG and TG; K had negative correlations with FBG; EPL had negative correlations with FBG and low-density lipoprotein (LDL); and CI had positive correlations with FBG and LDL. TEG may be a useful indicator of blood coagulation dysfunction in these patients rather the healthy individuals.

Electrochemical oxidative N-H/P-H cross-coupling with H2 evolution towards the synthesis of tertiary phosphines.

Tertiary phosphines(iii) find widespread use in many aspects of synthetic organic chemistry. Herein, we developed a facile and novel electrochemical oxidative N-H/P-H cross-coupling method, leading to a series of expected tertiary phosphines(iii) under mild conditions with excellent yields. It is worth noting that this electrochemical protocol features very good reaction selectivity, where only a 1 : 1 ratio of amine and phosphine was required in the reaction. Moreover, this electrochemical protocol proved to be practical and scalable. Mechanistic insights suggested that the P radical was involved in this reaction.

Electrochemical Difunctionalization of Terminal Alkynes: Access to 1,4-Dicarbonyl Compounds.

1,4-Dicarbonyl compounds are versatile scaffolds for the heterocycle synthesis, including the Paal-Knorr reaction. Herein, a feasible electrosynthesis method to access 1,4-dicarbonyl compounds has been developed from simple alkynes and 1,3-dicarbonyl compounds. When the undivided cell is combined with the constant current mode, aryl alkynes containing numerous medicinal motifs with 1,3-dicarbonyl esters or ketones react smoothly. External oxidant and catalyst-free conditions conform to the requirements of green synthesis.

Impact of Diabetes Mellitus on Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia Patients: A Meta-Analysis.

Background: Benign prostatic hyperplasia (BPH) is a disease that causes lower urinary tract symptoms (LUTS), which are the most common urological problem in approximately one-third of the male population aged over 50 years. Some studies have suggested that diabetes may be a risk factor for the development of BPH. However, whether diabetes aggravates the LUTS of BPH patients is still controversial. Aim: To investigate the impact of diabetes mellitus on LUTS in BPH patients. Methods: A literature search was conducted using Web of Science, Embase, PubMed, and China National Knowledge Infrastructure literature databases. This meta-analysis was registered in PROSPERO (registration number: CRD 42020200794). Fixed- or random-effects models were used for analysis according to heterogeneity. The results of the systematic analysis are presented as weighted mean difference (WMD) with the corresponding 95% confidence intervals (CI). Results: In total, 1308 studies were retrieved from databases and 18 articles comprising 1685 cases and 4653 controls were selected for meta-analysis. The results of the meta-analysis showed that the International Prostate Symptom Score (IPSS) value and prostate volume of BPH patients with diabetes was significantly higher than that of BPH patients without diabetes. Conclusions: This systematic review is the first to evaluate the impact of diabetes mellitus on LUTS in BPH patients. The results of our meta-analysis support the hypothesis that LUTS in BPH patients is increased in patients with diabetes mellitus compared with controls, which suggests that physicians should pay more attention to BPH patients with diabetes mellitus. Systematic Review Registration: PROSPERO [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=200794], identifier CRD 42020200794.