ortho-Alkynyl Benzyl Alcohols as C6 Synthons in Regioselective Construction of Polysubstituted Naphthalenes.

A straightforward methodology for the assembly of polysubstituted naphthalenes from ortho-alkynyl benzyl alcohols, enabled by using catalytic amounts of Tf2O, has been developed. This transformation not only features transition-metal free and without using other bases and additives but also provides a new synthetic application for ortho-alkynyl benzyl alcohols, i.e., as C6 synthons for the construction of PAHs.

Effects of organic pollutants on struvite crystallization kinetics and the molecular mechanism of inhibition on crystal growth.

The abilities of improving phosphorus (P) resources sustainability and reducing water eutrophication make struvite crystallization technology attract increasing interest in wastewater treatment, but struvite crystallization process may be affected by various impurities in wastewater. In this study, the effects of nine representative ionic surfactants including three types (anionic, cationic and zwitterionic) on crystallization kinetics and product quality of struvite were investigated, and the influencing mechanism was further probed. The results demonstrated that anionic surfactants significantly inhibit crystal growth so as to reduce crystal size especially in a-axis direction, change crystal morphology and decrease P recovery efficiency, and also lead to a slight decline in product purity. In contrast, cationic and zwitterionic surfactants have no obvious influence on the formation of struvite. A series of experimental characterizations and molecular simulations collectively revealed that the inhibition of crystal growth by anionic surfactants is attributed to the adsorption of anionic surfactant molecules on struvite crystal surface and subsequent blockage of active growth sites. The binding ability of surfactant molecules with the Mg2+ exposed on struvite crystal surface was highlighted to be the most essential factor determining the adsorption behavior and adsorption capacity. Anionic surfactants with stronger binding ability with Mg2+ have more intense inhibitory effect, but a large molecular volume of anionic surfactants will weaken the adsorption capacity on crystal surface so as to reduce the inhibitory effect. Contrastively, cationic and zwitterion surfactants without binding ability with Mg2+ have no inhibitory effect. These findings enable us to have a clearer understanding of the impact of organic pollutants on struvite crystallization and make a preliminary judgment on the organic pollutants that may have the ability to inhibit the crystal growth of struvite.

Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases.

Kynurenine pathway (KP), the primary pathway of L-tryptophan (Trp) metabolism in mammals, contains several neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Its imbalance involved in aging and neurodegenerative diseases (NDs) has attracted much interest in therapeutically targeting KP enzymes and KP metabolite-associated receptors, especially kynurenine monooxygenase (KMO). Currently, many agents have been discovered with significant improvement in animal models but only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD). In this review, we describe neuroactive KP metabolites, discuss the dysregulation of KP in aging and NDs and summarize the development of KP regulators in preclinical and clinical studies, offering an outlook of targeting KP for NDs treatment in future.

Calf muscle pump tensing as a novel maneuver to improve the diagnostic performance of detecting patent foramen ovale during transesophageal echocardiography.

Objective: The Valsalva maneuver is the most sensitive provocative maneuver for patent foramen ovale detection. However, nearly half of patients are unable to perform the Valsalva maneuver well. The aim of this study was to investigate the mechanism of action of calf muscle pump tensing (TENSE) as a novel patent foramen ovale (PFO) provocative maneuver and to evaluate the diagnostic value for PFO and the effect on right-to-left shunt volume compared with the Valsalva maneuver. Methods: This study prospectively investigated 171 patients who were highly suspected to have PFO clinically. Five patients with atrial septal defects newly diagnosed on transesophageal echocardiography (TEE) were excluded. 166 patients were injected with agitated saline under three provocative maneuvers: Valsalva maneuver, TENSE, and Valsalva + TENSE combined maneuver. The patients were divided into the effective Valsalva group (n = 93) and ineffective Valsalva group (n = 73) according to whether they could perform an effective Valsalva maneuver. TENSE consisted of the straightening of both lower limbs, and when the right atrium was filled with microbubbles, the patient performed instantaneous ankle dorsiflexion movements while maintaining dorsiflexion for 3-5 s. Results: Overall, the PFO detection rate of the Valsalva + TENSE combined maneuver (78 [50.1%]) was significantly higher than that of the Valsalva maneuver (51 [30.7%]) and TENSE maneuver (57 [34.3%]) (P < 0.001). In the patients who were able to perform an effective Valsalva maneuver, the PFO detection rate by TENSE was not significantly different from that by the Valsalva maneuver (Valsalva 37/93 [39.8%] vs. TENSE 31/93 [33.3%], P > 0.05), while for the patients who performed an ineffective Valsalva maneuver, the PFO detection rate by the TENSE maneuver was higher than that by the Valsalva maneuver (TENSE 26/73 [35.6%] vs. Valsalva14/73[19.2%], P = 0.017). Conclusion: TENSE is a simple and effective provocative maneuver in the diagnosis of PFO using TEE and can assist the Valsalva maneuver. For patients who cannot perform an effective Valsalva maneuver, TENSE can be an alternative to the Valsalva maneuver to some extent.

Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement.

Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 inhibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.

A High Triglyceride-Glucose Index Value Is Associated With an Increased Risk of Carotid Plaque Burden in Subjects With Prediabetes and New-Onset Type 2 Diabetes: A Real-World Study.

Background: The triglyceride-glucose (TyG) index has been proposed as a convincing indicator of insulin resistance and has been found to be associated with atherosclerosis among diabetic patients. However, the relationship between the TyG index and arteriosclerosis in subjects with prediabetes and new-onset type 2 diabetes (T2D) remains uncertain. The purpose of this study was to assess the degree of carotid plaque burden in patients with prediabetes and new-onset T2D and to investigate the association between the TyG index and the degree of carotid plaque burden in this population. Methods: This was a cross-sectional observational study that included 716 subjects aged 40-70 years old with prediabetes or new-onset T2D. Demographic, anthropometric, and laboratory measurements were collected. Participants underwent carotid arteriosclerosis evaluation by ultrasonography, and the degree of atherosclerosis was evaluated according to the carotid plaque burden. The TyG index was calculated. Results: The population was stratified into high or low TyG index groups according to the median TyG index value. Higher values were associated with a higher BMI and waist circumference as well as higher total cholesterol, triglyceride, low-density lipoprotein cholesterol, plasma glucose, glycated hemoglobin, fasting C-peptide, and C-reactive protein levels (P < 0.001). The high TyG index group had a higher atherosclerotic plaque burden than the low TyG index group (P < 0.001). Multiclassification logistic regression analysis showed that the TyG index was positively associated with a high plaque burden [odds ratio (OR): 16.706, 95% confidence interval (CI): 3.988-69.978, P = 0.000], while no association was found between the TyG index and a low/moderate plaque burden. This association remained consistent in the subgroup analysis. In multiple linear regression analysis, sex, age, and the TyG index were found to be independently associated with carotid plaque burden. For each unit increase in the TyG index, the risk of a high carotid plaque burden increased 1.595-fold. Conclusion: A high TyG index was positively associated with a high carotid plaque burden in subjects with prediabetes and new-onset T2D. Clinicians should pay close attention to the TyG index to help these patients receive the greatest benefit from early intervention.

Elasticity evaluation of the plantar fascia: A shear wave elastography study involving 33 early-stage plantar fasciopathy subjects.

Background: Plantar fasciopathy, the most common foot condition seen in elderly and athletic populations, can be diagnosed and differentially diagnosed with imaging modalities such as ultrasound shear wave elastography (SWE). However, standard guidelines for ultrasound elastography of the plantar fascia are lacking. The purpose of this study was to determine the impact of the region of interest (ROI) on the evaluation of the plantar fascia elasticity and confirm the screening accuracy of SWE in the early-stage of plantar fasciopathy. Methods: This was an observational case‒control study involving 50 feet of 33 early-stage plantar fasciopathy subjects (the plantar fasciopathy group) and 96 asymptomatic feet of 48 healthy volunteers (the non-pain group). Clinical information, including age, gender, height, weight, visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Scale score (AOFAS), and the symptom duration, were recorded. All participants underwent both conventional ultrasound and SWE evaluation. The plantar fascia elastic parameters included SWEsingle-point, calculated with a single-point ROI set at the greatest thickness of the plantar fascia, and SWEmulti-point, calculated by multipoint ROIs set continuously from the origin at the calcaneus to about 2 cm from the calcaneal origin. Results: The plantar fasciopathy group presented a higher VAS score (median [IQR), 4.00 (3.00) vs. 0.00 (0.00), p < 0.001] and lower AOFAS score [median (IQR), 79.50 (3.00) vs. 100.00 (10.00), p < 0.001] than the non-pain group. The median plantar fascia thickness of the plantar fasciopathy group was significantly greater than that of the non-pain group [median (IQR), 3.95 (1.37) mm vs 2.40 (0.60) mm, p < 0.001]. Abnormal ultrasound features, including echogenicity, border irregularities, and blood flow signals, were more prominent in the plantar fasciopathy group than in the non-pain group (29% vs. 0%, p < 0.001; 26% vs. 1%, p < 0.001; 12% vs. 0%, p < 0.001, respectively). Quantitative analysis of the plantar fascia elasticity revealed that the difference between the value of SWEsingle-point and SWEmultipoint was significant [median (IQR), 65.76 (58.58) vs. 57.42 (35.52) kPa, p = 0.02). There was a moderate and significant correlation between the value of SWEsingle-point and heel pain. However, there was no correlation between the value of SWEmultipoint and heel pain. Finally, we utilized the results of SWEsingle-point as the best elastic parameter reflecting clinical heel pain and found that SWEsingle-point could provide additional value in screening early-stage plantar fasciopathy, with an increase in sensitivity from 76% to 92% over conventional ultrasound alone. Additionally, compared with conventional ultrasound and SWE, the use of both improved the accuracy of screening for plantar fasciopathy. Although there were no significant differences in the negative predictive value of conventional ultrasound, SWE, and their combination, the positive predictive value when using both (90.20%) was significantly greater than that when using conventional ultrasound (74.50%) or SWE alone (76.50%). Conclusion: The plantar fascia elastic parameter calculated with single-point ROIs set at the greatest thickness of the plantar fascia is positively correlated with fascia feel pain. Single-point analysis is sufficient for the screening of the early-stage plantar fasciopathy using SWE. SWEsingle-point may provide additional valuable information for assessing the severity of plantar fasciopathy.

The Role of Imaging Techniques in Management of COVID-19 in China: From Diagnosis to Monitoring and Follow-Up.

In December 2019, an outbreak of coronavirus infection emerged in Wuhan, Hubei Province of China, which is now named Coronavirus Disease 2019 (COVID-19). The outbreak spread rapidly within mainland China and globally. This paper reviews the different imaging modalities used in the diagnosis and treatment process of COVID-19, such as chest radiography, computerized tomography (CT) scan, ultrasound examination, and positron emission tomography (PET/CT) scan. A chest radiograph is not recommended as a first-line imaging modality for COVID-19 infection due to its lack of sensitivity, especially in the early stages of infection. Chest CT imaging is reported to be a more reliable, rapid, and practical method for diagnosis of COVID-19, and it can assess the severity of the disease and follow up the disease time course. Ultrasound, on the other hand, is portable and involves no radiation, and thus can be used in critically ill patients to assess cardiorespiratory function, guide mechanical ventilation, and identify the presence of deep venous thrombosis and secondary pulmonary thromboembolism. Supplementary information can be provided by PET/CT. In the absence of vaccines and treatments for COVID-19, prompt diagnosis and appropriate treatment are essential. Therefore, it is important to exploit the advantages of different imaging modalities in the fight against COVID-19.

WITHDRAWN: Role of Cardiovascular Color Doppler Imaging Information Technology Under Artificial Intelligence Neural Network in the Diagnosis of Septic Shock Patients.

This article has been withdrawn at the request of the Editor-in-Chief. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Clinical Applications of Superb Microvascular Imaging in the Liver, Breast, Thyroid, Skeletal Muscle, and Carotid Plaques.

This article reviews the clinical applications of Superb Microvascular Imaging (SMI; Canon Medical Systems, Otawara, Japan) in the liver, breast, thyroid, skeletal muscle, and carotid plaques. Diseases that are closely associated with angiogenesis can be diagnosed by SMI in a relatively early phase, and using SMI can prevent adverse reactions associated with the contrast agents used in contrast-enhanced ultrasound. Super Microvascular Imaging also shows particular value in grading disease activities and monitoring therapeutic responses. Although SMI has some limitations, such as a lack of clinical standards, it can add information to conventional ultrasound examinations and may become a noninvasive alternative to invasive diagnostic procedures for many clinical conditions.