Visible Light-Induced, Nickel-Catalyzed Late-Stage 4-Alkylation of Hantzsch Esters with Alkyl Bromide.

Herein, visible light-induced, nickel-catalyzed direct functionalization of the Hantzsch esters (HEs) with readily accessible alkyl bromides has been successfully achieved by taking advantage of HE as the reductant and substrate through an aromatization-dearomatization process. In this strategy, the single electron reduction of alkyl bromides by reactive Ni(I) species is essential for the success of this late-stage transformation. A wide range of 4-alkyl-1,4-dihydropyridines were rapidly assembled in moderate to good yields under mild conditions, rendering this photoinduced approach attractive for synthetic and medicinal chemistry.

Amine-Borane-Mediated, Nickel/Photoredox-Catalyzed Cross-Electrophile Coupling between Alkyl and Aryl Bromides.

Nickel/photoredox catalysis has emerged as a powerful platform for exploring nontraditional and challenging cross-couplings. Herein, a metallaphotoredox catalytic protocol has been developed on the basis of a tertiary amine-ligated boryl radical-induced halogen atom transfer process under blue-light irradiation. A wide variety of aryl and heteroaryl bromides featuring different functional groups and pharmaceutical moieties were facilely coupled to rapidly install C(sp3)-enriched aromatic scaffolds. The compatibility of Lewis base-ligated borane with nickel catalysis was well exemplified to extend the chemical space for Ni-catalyzed cross-electrophile coupling.

Phosphine-Mediated Morita-Baylis-Hillman-Type/Wittig Cascade: Access to E-Configured 3-Styryl- and 3-(Benzopyrrole/furan-2-yl) Quinolinones.

A phosphine-mediated, well-designed Morita-Baylis-Hillman-type/Wittig cascade for the rapid assembly of a quinolinone framework from benzaldehyde derivatives is developed for the first time. By rationally combining I2/NIS-mediated cyclization, biologically relevant 3-(benzopyrrole/furan-2-yl) quinolinones were facilely synthesized in a one-pot process by starting from 3-styryl-quinolinones bearing an o-hydroxy/amino group, significantly expanding the chemical space of this privileged skeleton. Further utility of this protocol is illustrated by successfully performing this transformation in a catalytic manner through in situ reduction of phosphine oxide by phenylsilane.

Prevalence and associated factors of suicidal ideation among college students during the COVID-19 pandemic in China: a 3-wave repeated survey.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic, a major public health crisis, harms individuals' mental health. This 3-wave repeated survey aimed to examine the prevalence and correlates of suicidal ideation at different stages of the COVID-19 pandemic in a large sample of college students in China. METHODS: Using a repeated cross-sectional survey design, we conducted 3 online surveys of college students during the COVID-19 pandemic at 22 universities in Guandong, China. The 3 surveys were conducted during the outbreak period (T1: 3 February to 10 February 2020, N = 164,101), remission period (T2: 24 March to 3 April 2020, N = 148,384), and normalized prevention and control period (T3: 1 June to 15 June 2020, N = 159,187). Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire-9. A range of suicide-related factors was assessed, including sociodemographic characteristics, depression, anxiety, insomnia, pre-existing mental health problems, and COVID-19-related factors. RESULTS: The prevalence of suicidal ideation was 8.5%, 11.0% and 12.6% at T1, T2, and T3, respectively. Male sex (aOR: 1.35-1.44, Ps < 0.001), poor self-perceived mental health (aOR: 2.25-2.81, Ps < 0.001), mental diseases (aOR: 1.52-2.09, P < 0.001), prior psychological counseling (aOR: 1.23-1.37, Ps < 0.01), negative perception of the risk of the COVID-19 epidemic (aOR: 1.14-1.36, Ps < 0.001), depressive symptoms (aOR: 2.51-303, Ps < 0.001) and anxiety symptoms (aOR: 1.62-101.11, Ps < 0.001) were associated with an increased risk of suicidal ideation. CONCLUSION: Suicidal ideation appeared to increase during the COVID-19 pandemic remission period among college students in China. Multiple factors, especially mental health problems, are associated with suicidal ideation. Psychosocial interventions should be implemented during and after the COVID-19 pandemic to reduce suicide risk among college students.

An aryl thiol-vinyl azide coupling reaction and a thiol-vinyl azide coupling/cyclization cascade: efficient synthesis of ß-ketosulfides and arene-fused 5-methylene-2-pyrrolidinone derivatives.

The addition reaction of thiol to vinyl azide has been extensively studied. Variously substituted aryl thiols are all viable for this coupling process. The scope of the other partner is successfully expanded from α-aryl vinyl azide to α-alkyl vinyl azide. A thiol-vinyl azide coupling/cyclization cascade is realized with substituted aryl vinyl azides carrying a 2-methoxycarbonyl group. The value of ß-ketosulfide products was demonstrated by its application in S-heterocycle synthesis.

A phosphine-catalysed one-pot domino sequence to access cyclopentene-fused coumarins.

A novel phosphine-catalysed, one-pot domino approach for the annulation of 2-formylphenyl alkynoates with activated methylene compounds to construct various cyclopentene-fused dihydrocoumarins is reported. This developed strategy provides a facile and efficient approach for the synthesis of structurally complex coumarins from inexpensive and readily available alkynoates.

Cytotoxic gelsedine-type indole alkaloids from Gelsemium elegans.

A chemical investigation on the 95% ethanol extract of the aerial part of Gelsemium elegans resulted in the isolation of three new gelsedine-type indole alkaloids, 14ß-hydroxygelselenidine (1), 11-methoxygelseziridine (2), and 14ß-hydroxygelsedethenine (3). Structural elucidation of all the compounds was accomplished by spectral methods such as 1 D and 2 D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against five human non-small-cell lung cancer cell lines. Consequently, alkaloid 3 exhibited cytotoxic activities for all tested tumor cell lines with IC50 values from 8.3 to 9.8 µM. [Formula: see text].

Stereoselective synthesis of all-cis boryl tetrahydroquinolines via copper-catalyzed regioselective addition/cyclization of o-aldiminyl cinnamate with B2Pin2.

A copper catalyzed intramolecular 1,2-carboboration of o-aldiminyl cinnamate has been realized in both regio- and stereoselective fashions. This reaction provides a convenient entry to highly valuable and otherwise challenging cis-2,3,4-trisubstituted tetrahydroquinolines carrying a 4-boryl group. An unusual non-Michael addition intermediate or alternatively, a cyclic enolate is proposed to account for the intriguing all-cis configuration in the final products.

Anion Channel Inhibitor NPPB-Inhibited Fluoride Accumulation in Tea Plant (Camellia sinensis) Is Related to the Regulation of Ca²âº, CaM and Depolarization of Plasma Membrane Potential.

Tea plant is known to be a hyper-accumulator of fluoride (F). Over-intake of F has been shown to have adverse effects on human health, e.g., dental fluorosis. Thus, understanding the mechanisms fluoride accumulation and developing potential approaches to decrease F uptake in tea plants might be beneficial for human health. In the present study, we found that pretreatment with the anion channel inhibitor NPPB reduced F accumulation in tea plants. Simultaneously, we observed that NPPB triggered Ca(2+) efflux from mature zone of tea root and significantly increased relative CaM in tea roots. Besides, pretreatment with the Ca(2+) chelator (EGTA) and CaM antagonists (CPZ and TFP) suppressed NPPB-elevated cytosolic Ca(2+) fluorescence intensity and CaM concentration in tea roots, respectively. Interestingly, NPPB-inhibited F accumulation was found to be significantly alleviated in tea plants pretreated with either Ca(2+) chelator (EGTA) or CaM antagonists (CPZ and TFP). In addition, NPPB significantly depolarized membrane potential transiently and we argue that the net Ca(2+) and H⁺ efflux across the plasma membrane contributed to the restoration of membrane potential. Overall, our results suggest that regulation of Ca(2+)-CaM and plasma membrane potential depolarization are involved in NPPB-inhibited F accumulation in tea plants.

Al(3+) -promoted fluoride accumulation in tea plants (Camellia sinensis) was inhibited by an anion channel inhibitor DIDS.

BACKGROUND: Generally, tea plants are grown in acid soil which is rich in aluminum (Al) and fluoride (F). A recent publication showed that pretreatment with Al(3+) promoted F accumulation in tea plants by increasing endogenous Ca(2+) and calmodulin (CaM). A high level of F in tea leaves not only impairs tea quality but also might pose a health risk for people drinking tea regularly. Therefore it is important to try to find some clues which might be beneficial in controlling F accumulation in tea plants grown in acid soil (Al(3+) ). RESULTS: It was found that diisothiocyanostilbene-2,2-disulfonic acid (DIDS) significantly reduced Al(3+) -promoted F accumulation in tea plants. Additionally, Al(3+) plus DIDS treatment stimulated significantly higher Ca(2+) efflux and decreased the CaM level in tea roots compared with Al(3+) treatment. Besides, significantly higher depolarization of membrane potential was shown in tea roots treated with Al(3+) plus DIDS than in those treated with Al(3+) , as well as higher net total H(+) efflux and plasma membrane H(+) -ATPase activity. CONCLUSION: Al(3+) -promoted F accumulation in tea plants was inhibited by an anion channel inhibitor DIDS. Ca(2+) /CaM and membrane potential depolarization may be the components involved in this process. © 2016 Society of Chemical Industry.

Sleep disturbance and attempted suicide in rural China: a case-control study.

This study aimed to examine the association between sleep disturbance and attempted suicide in rural China. The study group included 409 suicide attempters from six rural counties in Shandong Province, China and an equal number of controls matched on age, sex, and residency. Sleep disturbance was assessed by the item "sleep restless" in the Center for Epidemiologic Studies Depression Scale. Sleep disturbance was reported more frequently in suicide attempters than in controls (1-2 days/week, 9.0% vs. 4.4%; 3-4 days/week, 11.5% vs. 2.4%; ≥5 days/week, 30.3% vs. 7.5%, χ 2= 128.72, p < 0.001). Suicide risk was significantly associated with increased frequency of sleep disturbance (OR = 3.98, 95% CI = 1.62-9.74 for 1-2 days/week; OR = 3.28, 95% CI = 1.21-8.84 for 3-4 days/week; OR = 2.41, 95% CI = 1.26-4.60 for ≥5 days/week) even after adjusting for potential psychosocial confounding factors and mental disorders. This finding may have important implications for early intervention and prevention of suicide.

Beck Hopelessness Scale: Psychometric Properties Among Rural Chinese Suicide Attempters and Non-Attempters.

The authors recruited 401 suicide attempters from general hospitals and 409 matched non-attempters to evaluate the psychometric properties of the Beck Hopelessness Scale (BHS) in rural China. All participants completed the BHS, Center for Epidemiologic Studies Depression Scale (CES-D), and Trait Anxiety Inventory (TAI). Suicide attempters had higher BHS scores than non-attempters. Cronbach's alpha coefficients were satisfactory and BHS scores significantly correlated to CES-D and TAI scores. Confirmatory factor analysis supported a four-factor model for suicide attempters and a five-factor model for non-attempters. The BHS is satisfactory in assessing hopelessness among suicide attempters in rural China.

Rationality and effectiveness of transarterial chemoembolization as an initial treatment for BCLC B stage HBV-related hepatocellular carcinoma.

BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is recommended as standard care for intermediate hepatocellular carcinoma (HCC). We analyse the rationality and effectiveness of TACE with BCLC B stage HBV-related HCC in a large cohort. METHODS: A total of 1516 patients with BCLC B stage from 7724 HBV-related HCCs who received TACE as initial treatment were retrospectively studied. The treatment response was assessed by the mRECIST criteria. The overall survival was calculated with life-table method and compared with the Mantel-Cox test. The prognostic factors were assessed using Cox proportional hazards. RESULTS: The 1-, 3- and 5-year overall survival rates were 84%, 29% and 19% respectively for all patients. Alpha-foetoprotein, Child-Pugh classification, tumour size and number were independent prognostic factors. The 5-year survival for patients with CR, PR, SD and PD were 39%, 19%, 2% and 0%, respectively (P < 0.0001). Child-Pugh A liver function (P = 0.002) and smaller tumour (P < 0.0001) were associated with CR/PR response. After TACE, the 5-year survival rates for patients who received surgical resection, local ablation, repeated TACE and other therapies were 52%, 29%, 12%, 10% respectively (P < 0.0001). In 328 CR patients, the prognosis of 151 patients received surgical resection is better than 177 patients not undergo liver resection (5-year survival: 52% & 27%, P < 0.0001). CONCLUSIONS: Transarterial chemoembolization is a safe and efficacious treatment for BCLC B stage HBV-related HCC. A low AFP level, small tumour, low tumour number and good liver function predicted good survival. Tumour response after initial TACE, an independent prognostic factor of overall survival, was associated with tumour extent and influenced subsequent treatment.

Programmed system for fatigue life prediction of excavator turntables based on multi-body dynamics and finite element analysis.

This study focuses on predicting mechanical fatigue in excavator turntables, critical components susceptible to failure due to variable operational loads. While conventional methods like finite element analysis(FEA) and multiaxial fatigue criteria have been used, they are limited by the complexity and cost of obtaining real operational load spectra. To address this challenge, our research presents a comprehensive approach that integrates multi-body dynamics modeling, finite element analysis, and MATLAB-based fatigue life prediction systems. Our methodology involves creating a finite element model for stress analysis, synthesizing load spectra from operational data, and utilizing Weibull distribution to analyze load magnitude probabilities. Subsequently, MATLAB imported the load spectrum and built the fatigue prediction framework to finalize the analysis. Furthermore, we have fully open-sourced our code on an open platform, incorporating default load profiles and predictive models within the code. Key findings pinpoint areas prone to stress concentration and fatigue. Key findings identify stress concentration areas and fatigue-prone regions, providing valuable insights for design optimization and durability improvement.

Lessons from an elderly patient with pulmonary embolism caused by protein S deficiency: a case report.

BACKGROUND: Lower limb deep vein thrombosis (DVT) concurrent with pulmonary embolism (PE) is perilous, particularly in the elderly, exhibiting heterogeneity with thrombophilia mutations. Tailored treatment is essential, yet sudden deaths complicate causative factor elucidation. This report emphasizes genetic testing necessity in PE patients with thrombophilia indicators, facilitating cause identification, personalized treatment guidance, and family education. CASE PRESENTATION: This study details a 75-year-old Chinese woman with DVT and PE, where genetic testing identified thrombophilia, guiding personalized treatment decisions. RESULTS: Upon admission, the patient, after over 10 days of bed rest, presented chest tightness, shortness of breath, and unilateral leg swelling. Diagnostic measures revealed DVT and a substantial PE. Genetic testing identified a PROS1 gene C200A>C mutation, reducing protein S activity. Following 2 weeks of anticoagulation and inferior vena cava filter insertion, the patient, discharged, initiated lifelong anticoagulant therapy. A 1-year follow-up showed no recurrent thrombotic events. Family members carrying the mutation received informed and educational interventions. CONCLUSION: Genetic testing for thrombophilic predisposition post-PE is crucial, elucidating etiology, guiding individualized treatment, and playing a pivotal role in family education.

Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Noncoding RNA network crosstalk in organ fibrosis.

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.

The landscape of histone modification in organ fibrosis.

An increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues are the primary pathological alterations linked to organ fibrosis. If fibrosis is not treated, organ structure is destroyed, function can decline, or even fail, posing a serious risk to human life and health. Numerous organs develop fibrosis, and organ fibroproliferative illnesses account for almost 45% of patient deaths from various diseases in the industrialized world, as well as a major cause of disability and mortality in many other diseases. Recently, it has become evident that histone modification is an important way to regulate gene expression in organ fibrosis. Histone modifications alter the structure of chromatin, thereby affecting gene accessibility. Histone acetylation modifications relax chromatin, making it easier for gene transcription factors to access DNA, thereby promoting gene transcription. In addition, histone modifications recruit other proteins to interact with chromatin to form complexes that further regulate gene expression. Histone methylation modifications recruit methylation-reading proteins that recognize methylation marks and alter gene expression status. It not only affects the normal physiological function of cells, but also plays an important role in organ fibrosis. This article reviews the important role played by histone modifications in organ fibrosis and potential therapeutic approaches.

Photoredox/Nickel Dual Catalysis-Enabled Aryl Formylation with 2,2-Dimethoxy-N,N-dimethylethan-1-amine as CO Source.

Herein, a dual photoredox/nickel catalyzed formylation of aryl bromide with commercially available 2,2-dimethoxy-N,N-dimethylethan-1-amine as an effective CO source has been successfully achieved, delivering a series of aromatic aldehydes in moderate to good yields. Compared with the traditional reductive carbonylation process, this newly designed synthetic protocol provides a straightforward toolbox to access aromatic aldehydes, obviating the use of carbon monoxide and stoichiometric reductants. Finally, the utility of this direct formylation reaction was demonstrated in the pharmaceutical analogue synthesis.

New aspects of the epigenetic regulation of EMT related to pulmonary fibrosis.

Pulmonary fibrosis is a chronic and progressive fibrotic disease that results in impaired gas exchange, ventilation, and eventual death. The pro-fibrotic environment is instigated by various factors, leading to the transformation of epithelial cells into myofibroblasts and/or fibroblasts that trigger fibrosis. Epithelial mesenchymal transition (EMT) is a biological process that plays a critical role in the pathogenesis of pulmonary fibrosis. Epigenetic regulation of tissue-stromal crosstalk involving DNA methylation, histone modifications, non-coding RNA, and chromatin remodeling plays a key role in the control of EMT. The review investigates the epigenetic regulation of EMT and its significance in pulmonary fibrosis.