Abstract
We herein report a method for the synthesis of 1,4‐dicarbonyl compounds using light‐activated electron donor‐acceptor (EDA) complexes. This multi‐component reaction involves the ...photoactivation of EDA complexes formed by carboxylic acid derivatives, triphenylphosphine, and sodium iodide, resulting in single‐electron reduction. The subsequent decarboxylation fragmentation leads to the formation of nucleophilic alkyl free radicals, which can undergo sequential radical coupling reactions with electron‐deficient and electron‐rich olefins. This method has been successfully applied to various aliphatic carboxylic acid derivatives, including tertiary, secondary, and primary ones, as well as multiple types of electron‐deficient olefins and enol silyl ethers. The entire process is conducted under mild conditions, indicating its potential for the synthesis of valuable synthetic compounds.
This article sheds light on the ongoing employment stagnation in the United States by investigating the links between the rise of finance and firm employment dynamics during the 1982–2005 period. I ...argue that the rise of finance marginalized the role of labor in revenue generating and sharing processes, which led to employment stagnation among the largest nonfinancial firms in the United States. Evidence suggests that increasing investment in financial assets depresses the workforce size. The growing dependence on debt reprioritizes the order of distribution, heightening the need for workforce reduction. The increasing rewards for shareholders generate a downsize-and-distribute spiral, in which labor expense becomes a primary target of cost-cutting strategies. Further analysis indicates that production and service workers are more vulnerable to shifts associated with the rise of finance than managers and professionals.
The connection between vitamin D to non-alcoholic fatty liver disease (NAFLD) is still unclear. Herein, the relationship of vitamin D with NAFLD and liver fibrosis (LF) detected by vibration ...controlled transient elastography was investigated in US adults.
The National Health and Nutrition Examination Survey of 2017-2018 was employed for our analysis. Participants were categorized as having either vitamin D deficiency (<50 nmol/L) or vitamin D sufficiency (≥50 nmol/L). A controlled attenuation parameter score of ≥ 263 dB/m was employed to define NAFLD. Significant LF was identified by the liver stiffness measurement value of ≥ 7.9 kPa. Multivariate logistic regression was adopted to explore the relationships.
Among the 3407 participants, the prevalence of NAFLD and LF was 49.63% and 15.93% respectively. Compared to participants without NAFLD, no significant difference in serum vitamin D was observed in NALFD participants (74.26 vs. 72.24 nmol/L; p = 0.21). Using multivariate logistic regression analysis, no obvious connection of vitamin D status to NAFLD (sufficiency vs. deficiency, OR 0.89, 95%CI 0.70-1.13) was discovered. However, among NAFLD participants, the sufficiency of vitamin D represents a lower LF risk (OR 0.56, 95%CI 0.38-0.83). When evaluated in quartiles, in comparison to the lowest quartile, high vitamin D represents low LF risk in a dose-dependent manner (Q2 vs. Q1, OR 0.65, 95%CI 0.37-1.14; Q3 vs. Q1, OR 0.64, 95%CI 0.41-1.00; Q4 vs. Q1, OR 0.49, 95%CI 0.30-0.79).
No relationship was found between vitamin D and CAP-defined NAFLD. However, a positive connection of the high serum vitamin D to the reduced LF risk was found among NAFLD subjects.
Key messages:
Our study found no relationship between vitamin D and CAP-defined NAFLD in US adults.
High serum vitamin D was inversely associated with liver fibrosis in a dose-dependent manner among NAFLD participants.
The 2008 collapse of the world financial system, while proximately linked to the housing bubble and risk-laden mortgage backed securities, was a consequence of the financialization of the U.S. ...economy since the 1970s. This article examines the institutional and income dynamics associated with the financialization of the U.S. economy, advancing a sociological explanation of income shifts into the finance sector. Complementary developments include banking deregulation, finance industry concentration, increased size and scope of institutional investors, the shareholder value movement, and dominance of the neoliberal policy model. As a result, we estimate that between 5.8 and 6.6 trillion dollars were transferred to the finance sector since 1980. We conclude that understanding inequality dynamics requires attention to market institutions and politics.
Primary liver cancer, particularly hepatocellular carcinoma (HCC) remains a significant disease worldwide. It is among the top three causes of cancer death in the Asia Pacific region because of the ...high prevalence of its main etiological agents, chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In this region, the incidence of HCC has been static over recent decades. Older age is a major risk factor; the incidence increasing sharply after age 40 years. There is a male predilection, with male to female ratio of 3:1, except in elderly Japanese with equal sex incidence or female predominance. In most Asia‐Pacific countries, chronic HBV infection accounts for 75–80% of cases; Japan, Singapore and Australia/New Zealand are exceptions because of higher prevalence of HCV infection. In spite of advances in surgery, liver transplantation and newer pharmaco/biological therapies, the survival rate has improved only slightly over recent decades, and this could be attributable to earlier diagnosis (‘lead‐time bias’). The majority of patients present with advanced diseases, hence reducing the chance of curative treatment. The importance of HCC may decrease in two to three decades when the prevalence of chronic HBV infection decreases as a result of the universal HBV vaccination programs implemented in late 1980s in most Asia‐Pacific countries, and because of reduced incidence of medical transmission of HCV. However, transmission of HCV by injection drug use, and rising prevalence of obesity and diabetes, both independent risk factors for HCC, may partly offset this decline.
We investigate the dynamics of neutral timelike particles around a hairy black hole in Horndeski’s theory, which is characterized by a coupling parameter with the dimension of length. With deriving ...the particles’ relativistic periastron precessions, a preliminary bound on the hairy black hole is obtained by using the result of the S2 star’s precession with GRAVITY. It is tighter than the previous result constrained by the shadow size from EHT observations of M87* by about 3–4 orders of magnitude. We also analyse the particles’ periodic motions around the hole in the strong gravitational field. It clearly shows that small variations in the coupling parameter can make the neutral particles’ motions back and forth from the quasi-periodic orbits to the periodic orbits or no bound orbit. Our present work might provide hints for distinguishing the hairy black hole in Horndeski’s theory from the classical hole by using the particles’ dynamics in the strong gravitational field.
Severe acute respiratory infection (SARI), a significant global health concern, imposes a substantial disease burden. In China, there is inadequate data concerning the monitoring of respiratory ...pathogens, particularly bacteria, among patients with SARI. Therefore, this study aims to delineate the demographic, epidemiological, and aetiological characteristics of hospitalised SARI patients in Central China between 2018 and 2020.
Eligible patients with SARI admitted to the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2020 were included in this retrospective study. Within the first 24 h of admission, respiratory (including sputum, nasal/throat swabs, bronchoalveolar lavage fluid, thoracocentesis fluid, etc.), urine, and peripheral blood specimens were collected for viral and bacterial testing. A multiplex real-time polymerase chain reaction (PCR) diagnostic approach was used to identify human influenza virus, respiratory syncytial virus, parainfluenza virus, adenovirus, human bocavirus, human coronavirus, human metapneumovirus, and rhinovirus. Bacterial cultures of respiratory specimens were performed with a particular focus on pathogenic microorganisms, including S. pneumoniae, S. aureus, K. pneumoniae, P. aeruginosa, Strep A, H. influenzae, A. baumannii, and E. coli. In cases where bacterial culture results were negative, nucleic acid extraction was performed for PCR to assay for the above-mentioned eight bacteria, as well as L. pneumophila and M. pneumoniae. Additionally, urine specimens were exclusively used to detect Legionella antigens. Furthermore, epidemiological, demographic, and clinical data were obtained from electronic medical records.
The study encompassed 1266 patients, with a mean age of 54 years, among whom 61.6% (780/1266) were males, 61.4% (778/1266) were farmers, and 88.8% (1124/1266) sought medical treatment in 2020. Moreover, 80.3% (1017/1266) were housed in general wards. The most common respiratory symptoms included fever (86.8%, 1122/1266) and cough (77.8%, 986/1266). Chest imaging anomalies were detected in 62.6% (792/1266) of cases, and 58.1% (736/1266) exhibited at least one respiratory pathogen, with 28.5% (361/1266) having multiple infections. Additionally, 95.7% (1212/1266) of the patients were from Henan Province, with the highest proportion (38.3%, 486/1266) falling in the 61-80 years age bracket, predominantly (79.8%, 1010/1266) seeking medical aid in summer and autumn. Bacterial detection rate (39.0%, 495/1266) was higher than viral detection rate (36.9%, 468/1266), with the primary pathogens being influenza virus (13.8%, 175/1266), K. pneumoniae (10.0%, 127/1266), S. pneumoniae (10.0%, 127/1266), adenovirus (8.2%, 105/1266), P. aeruginosa (8.2%, 105/1266), M. pneumoniae (7.8%, 100/1266), and respiratory syncytial virus (7.7%, 98/1266). During spring and winter, there was a significant prevalence of influenza virus and human coronavirus, contrasting with the dominance of parainfluenza viruses in summer and autumn. Respiratory syncytial virus and rhinovirus exhibited higher prevalence across spring, summer, and winter. P. aeruginosa, K. pneumoniae, and M. pneumoniae were identified at similar rates throughout all seasons without distinct spikes in prevalence. However, S. pneumoniae showed a distinctive pattern with a prevalence that doubled during summer and winter. Moreover, the positive detection rates of various other viruses and bacteria were lower, displaying a comparatively erratic prevalence trend. Among patients admitted to the intensive care unit, the predominant nosocomial bacteria were K. pneumoniae (17.2%, 43/249), A. baumannii (13.6%, 34/249), and P. aeruginosa (12.4%, 31/249). Conversely, in patients from general wards, predominant pathogens included influenza virus (14.8%, 151/1017), S. pneumoniae (10.4%, 106/1017), and adenovirus (9.3%, 95/1017). Additionally, paediatric patients exhibited significantly higher positive detection rates for influenza virus (23.9%, 11/46) and M. pneumoniae (32.6%, 15/46) compared to adults and the elderly. Furthermore, adenovirus (10.0%, 67/669) and rhinovirus (6.4%, 43/669) were the primary pathogens in adults, while K. pneumoniae (11.8%, 65/551) and A. baumannii (7.1%, 39/551) prevailed among the elderly, indicating significant differences among the three age groups.
In Central China, among patients with SARI, the prevailing viruses included influenza virus, adenovirus, and respiratory syncytial virus. Among bacteria, K. pneumoniae, S. pneumoniae, P. aeruginosa, and M. pneumoniae were frequently identified, with multiple infections being very common. Additionally, there were substantial variations in the pathogen spectrum compositions concerning wards and age groups among patients. Consequently, this study holds promise in offering insights to the government for developing strategies aimed at preventing and managing respiratory infectious diseases effectively.
We developed metal- and photosensitizer-free cross-dehydrogenative coupling (CDC) systems to promote the cleavage of strong C(sp
3
)H bonds through a distinct non-photoredox engaged hydrogen atom ...transfer (HAT) process. Mechanistic experiments indicate that this reaction predominantly proceeds through an energy transfer mechanism from excited-state heteroarenes to peroxides, with the direct irradiation of peroxides serving as a supplementary and secondary pathway to promote homolysis of the OO bond. The resulting oxygen radicals undergo HAT from a substrate C-H bond, followed by addition of the obtained alky radical to heteroarenes, facilitating the formation of the key C-C bond. The conclusion that
tert
-butyl peroxybenzoate (TBPB) and heteroarenes are the optimal energy transfer pairs was drawn by screening a series of peroxides. In addition to its efficiency and step-economy, this approach boasts environmental advantages, making it suitable for the late-stage functionalization of pharmaceuticals and drug-like molecules, while accommodating a wide range of functional groups.
This study introduces a novel, eco-friendly method for Minisci alkylation without harmful catalysts, advancing sustainable pharmaceutical synthesis through energy transfer from heteroarenes to peroxide, offering significant environmental benefits.
In desmoplastic melanoma, tumor cells and tumor-associated fibroblasts are the major dominators playing a critical role in the fibrosis morphology as well as the immunosuppressive tumor ...microenvironment (TME), compromising the efficacy of therapeutic options. To overcome this therapeutic hurdle, we developed an innovative chemo-immunostrategy based on targeted delivery of mitoxantrone (MIT) and celastrol (CEL), two potent medicines screened and selected with the best anticancer and antifibrosis potentials. Importantly, CEL worked in synergy with MIT to induce immunogenic tumor cell death. Here, we show that when effectively co-delivered to the tumor site at their optimal ratio by a TME-responsive nanocarrier, the 5:1 combination of MIT and CEL significantly triggered immunogenic tumor apoptosis and recovered tumor antigen recognition, thus eliciting overall antitumor immunity. Furthermore, the strong synergy benefitted the host in reduced drug exposure and side effects. Collectively, the nanocarrier-mediated chemo-immunotherapy successfully remodeled fibrotic and immunosuppressive TME, arrested cancer progression, and further inhibited tumor metastasis to major organs. The affected tumors remained dormant long after dosing stopped, resulting in a prolonged progression-free survival and sustained immune surveillance of the host bearing desmoplastic melanoma.
Sonodynamic therapy (SDT) has rapidly developed as a powerful alternative to traditional photodynamic therapy due to its intrinsically deeper tissue-penetration. However, single SDT dose is incapable ...of radical cure because the long-term hypoxia of tumor limits its therapeutic effect. Herein, we developed a biomimetic nanoplatform with dual pH/ultrasound response, homologous targeting and low phototoxicity for combined nitric oxide (NO) gas therapy with SDT to solve the problem. This nanoplatform is composed of zeolite imidazole framework-8 material embedded with nitrosoglutathione (GSNO) and chlorin e6 (Ce6) by one-step encapsulation, and then wrapped by homologous tumor cell membrane. In vitro and in vivo experiments indicate that the biomimetic nanoplatform has excellent biocompatibility and shows higher retention in tumor by homologous targeting. Importantly, it can sustainably release the encapsulated drug in acidic tumor microenvironment and accelerate degradation by ultrasound (US). Furthermore, NO released from GSNO and reactive oxygen species generated by Ce6, which are both triggered by US, react with each other to produce highly reactive peroxynitrite to inhibit the growth of tumor. Moreover, by repeated US irradiation, the tumor hypoxia can be relieved for a much-longer term, resulting in an effective gas-sonodynamic combined treatment. This study fully utilizes the advantages of US, providing a new strategy for high-performance cancer therapy.
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