Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Personalized analysis of human cancer multi-omics for precision oncology.

Multi-omics technologies, encompassing genomics, proteomics, and transcriptomics, provide profound insights into cancer biology. A fundamental computational approach for analyzing multi-omics data is differential analysis, which identifies molecular distinctions between cancerous and normal tissues. Traditional methods, however, often fail to address the distinct heterogeneity of individual tumors, thereby neglecting crucial patient-specific molecular traits. This shortcoming underscores the necessity for tailored differential analysis algorithms, which focus on particular patient variations. Such approaches offer a more nuanced understanding of cancer biology and are instrumental in pinpointing personalized therapeutic strategies. In this review, we summarize the principles of current individualized techniques. We also review their efficacy in analyzing cancer multi-omics data and discuss their potential applications in clinical practice.

The asymmetric impact of decision-making confidence on regret and relief.

When individuals make uncertain decisions, they often evaluate the correctness of their choices in what is referred to as decision-making confidence. The outcomes of such decision-making can lead to counterfactual thinking wherein alternative possible outcomes are contemplated. This, in turn, can elicit counterfactual emotions including upward and downward counterfactual thinking, which, respectively, refer to regret and relief. Decision-making confidence and counterfactual emotions have key effects on how individuals learn from the past and prepare for the future. However, there has been little understanding of how these experiences are related. For this study, 98 total adults were recruited with the goal of assessing the connections between decision-making confidence and sensations of regret and relief when completing a card-based gambling task. The results of this study suggest that decision-making confidence may reduce the intensity of relief while increasing the degree of regret experienced. These findings thus emphasize the important effect that decision confidence has on emotional processing.

PhosMap: An ensemble bioinformatic platform to empower interactive analysis of quantitative phosphoproteomics.

BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS)-based quantitative phosphoproteomics has been widely used to detect thousands of protein phosphorylation modifications simultaneously from the biological specimens. However, the complicated procedures for analyzing phosphoproteomics data has become a bottleneck to widening its application. METHODS: Here, we develop PhosMap, a versatile and scalable tool to accomplish phosphoproteomics data analysis. A standardized phosphorylation data format was created for data analyses, from data preprocessing to downstream bioinformatic analyses such as dimension reduction, differential phosphorylation analysis, kinase activity, survival analysis, and so on. For better usability, we distribute PhosMap as a Docker image for easy local deployment upon any of Windows, Linux, and Mac system. RESULTS: The source code is deposited at https://github.com/BADD-XMU/PhosMap. A free PhosMap webserver (https://huggingface.co/spaces/Bio-Add/PhosMap), with easy-to-follow fashion of dashboards, is curated for interactive data analysis. CONCLUSIONS: PhosMap fills the technical gap of large-scale phosphorylation research by empowering researchers to process their own phosphoproteomics data expediently and efficiently, and facilitates better data interpretation.

Diatomite supported highly-dispersed ZnO/Zn-co-embedded ZIF-8 derived porous carbon composites for adsorption desulfurization.

The metal organic framework (MOFs)-derived porous carbon materials with highly dispersed metal active sites were of the exclusive application foreground in many field, such as catalyst, electrochemistry, adsorption desulfurization and so on. However, the loss issue of metal active sites in MOFs frame was indispensable during the high temperature carbonization because of the lower boiling point of many metals, thus fundamentally affecting the atom-scale uniform distribution merit of MOFs-derived porous carbon materials. This work was to provide a novel strategy to address the loss issue of the active metal volatilization in the fabrication of MOFs-derived porous carbon materials. The ZnO nanosheets were pre-grown on the surface of diatomite by using in-situ microwave-assisted preparation, and thereafter the Zn-containing ZIF-8 particles covered the surface of ZnO nanosheets by virtue of the ZnO-induced growth. The results affirmed that the high content Zn-doped porous carbon materials were achieved and the Zn volatilization in MOFs was restrained on account of the occurrence of ZnO on diatomite (DE) surface during the carbonization. The adsorption desulfurization performance of the ZnO/Zn-embedded porous carbon materials/DE (ZnO/Zn/C@DE) was examined by the sulfur-containing compounds in simulated oil. The adsorption desulfurization performance investigation indicated that the ZnO/Zn/C@DE had the optimum adsorption capacities of 45.3 mg/g for benzothiophene and 37.4 mg/g for thiophene. Nonetheless, the competitive adsorption desulfurization finding of toluene in simulated oil showed that the adsorption capacities of ZnO/Zn/C@DE for TH and BT were dramatically descended, suggesting the presence of S-M interaction, wherein S stood for the S atom in a thiophene molecule and their analogs, and M for Zn atoms in porous carbon materials.

A dual-targeted Gd-based contrast agent for magnetic resonance imaging in tumor diagnosis.

Enhanced magnetic resonance imaging (MRI) has important clinical value in the diagnosis of tumors. Much effort has been made to improve the relaxivity and specificity of contrast agents (CAs) in tumor diagnosis over the past few decades. However, there is still a lack of CAs which not only enhance the signal intensity of tumors rather than surrounding tissues in MRI but also maintain a high signal intensity prolonged for a long time. Herein, we synthesized a dual-targeted CA, RGD-(DOTA-Gd)-TPP (RDP), in which RGD is used to target the αvß3 integrin receptor overexpressed in tumor cells and TPP is used to bind to a mitochondrion further. The structure of RDP was characterized and its properties, such as relaxivity and biosafety, were measured and in vitro and in vivo MRI assays were carried out. It has been proven that RDP has higher relaxivity of aqueous solution than Magnevist used in clinics. Moreover, RDP achieved higher signal intensity and a longer signal duration in tumor imaging. Therefore, RDP can be applied as the potential dual-targeted MRI CA for clinical tumor diagnosis.

Regioselective Diels-Alder Reactions of Anthracenes with Olefins via Visible Light Photocatalysis in a Homogeneous Solution.

Diels-Alder cycloaddition of anthracene with olefin is achieved in a homogeneous solution via energy transfer under visible light. A series of substrates including electroneutral styrene derivatives can be successfully converted into the corresponding cycloadducts in a head-to-head orientation with high to excellent yields. The high ortho-regioselectivity, mild condition, and broad substrate scope enable promising advances in organic transformation.

Hesperetin promotes bladder cancer cells death via the PI3K/AKT pathway by network pharmacology and molecular docking.

Patients with bladder cancer (BLCA) still show high recurrence after surgery and chemotherapy. Hesperetin (HE), as a natural compound, has attracted researchers' attention due to its low toxicity and easy access. However, the inhibitory effect of HE on BLCA remains unknown. The hub genes and enrichment pathways regulated by HE in the treatment of BLCA were predicted by network pharmacology. The molecular docking of HE and hub proteins was visualized. Colony and CCK8 assays were used to test cell proliferation, and BLCA migration was confirmed by transwell and wound healing assays. In addition, the occurrence of apoptosis and ferroptosis was demonstrated by Hoechst staining, transmission electron microscopy (TEM) and ROS (reactive oxygen species) assay. Western Blotting was performed to validate the hub proteins, target functions and pathways. SRC, PIK3R1 and MAPK1 were identified as hub targets for HE in BLCA, involving the PI3k/AKT pathway. Furthermore, HE inhibited the proliferation and migration of BLCA cells. The MMP2/MMP9 proteins were significantly inhibited by HE. The increased expression of Bax and cleaved caspase-3 indicated that HE could promote BLCA cell apoptosis. In addition, Hoechst staining revealed concentrated and illuminated apoptotic nuclei. The activation of ROS and the decline of GPX4 expression suggested that HE might induce ferroptosis as an anti-BLCA process. Shrunk mitochondria and apoptotic bodies were observed in BLCA cells treated with HE, with reduced or absent mitochondrial cristae. We propose for the first time that HE could inhibit the proliferation and migration of BLCA cells and promote apoptosis and ferroptosis. HE may act by targeting proteins such as SRC, PIK3R1 and MAPK1 and the PI3K/AKT pathway.

A candidate prognostic biomarker: TFEB inhibits tumor progression via elevating CDKN1A in bladder cancer.

Bladder cancer(BC) is among the most prevalent malignancies in the world, with 549,393 new cases documented in 2018, and most BC patients have a poor prognosis. Transcription factor EB (TFEB) is considered a crucial controller of lysosomal-associated diseases, but a growing number of research in recent years have reported that TFEB plays other functions in tumors independent of lysosomal autophagy. In this study, we aimed to assess whether TFEB is a biomarker for BC and a molecular target for BC therapy. TFEB was lowly expressed in BC tissues relative to paracancerous tissues, and its elevated expression was strongly associated to a better prognosis for BC patients. TFEB overexpression markedly suppressed cell proliferation, limited cell migration, and accelerated apoptosis. Tumor growth in vivo was also suppressed. Mechanistically, we found that TFEB promoted CDKN1A expression by binding to the upstream progenitor of the CDKN1A promoter, which was also dependent on p53. Finally, Immune cell infiltration in BC tissues, PDL-1 expression, and Single-cell RNA sequencing data revealed immunotherapy may have a positive correlation with TFEB expression. Our study identifies that TFEB regulates CDKN1A in BC and has a positive prognostic value, while its expression is also positively correlated with immune cell infiltration. Therefore, TFEB may represent a recent therapeutic target for BC.

Cu+-Doped PVA-Derived Mesoporous Carbon@Diatomite Adsorbent for Selective Adsorption Desulfurization.

Herein, we successfully constructed a Cu+-doped PVA-derived mesoporous carbon@diatomite (DE) composite by virtue of N2-suffered carbonization and self-reduction at a high temperature. The structure and composition of C/Cu@DE composite adsorbents were determined by a series of characterizations. The results affirmed that Cu+ species are highly scattered in PVA-derived mesoporous carbon, which covered the DE surface. The effect of carbonization temperature on the structure and composition of the C/Cu@DE composite adsorbents were intensively investigated, indicating that the C/Cu@DE composite at an 800 °C carbonization temperature (C/Cu@DE-800 °C) showed the formation of many Cu+ species and preferable hierarchical pore properties. The adsorption experiments of benzothiophene (BT) indicated that C/Cu@DE-800 °C possessed a better adsorption capacity. The adsorption behavior of BT onto C/Cu@DE-800 °C was investigated by a variety of adsorption times, initial concentrations, and recycle times, of which the largest adsorption capacity for BT attained 34.2 mg/g. Furthermore, the adsorption kinetics, intraparticle diffusion, adsorption isotherms, and adsorption thermodynamics of BT onto C/Cu@DE-800 °C was deeply studied, which contributed to the proposed adsorption mechanism.

Longitudinal detection of subcategorized CD44v6+ CTCs and circulating tumor endothelial cells (CTECs) enables novel clinical stratification and improves prognostic prediction of small cell lung cancer: A prospective, multi-center study.

Current management of small cell lung cancer (SCLC) remains challenging. Effective biomarkers are needed to subdivide patients presenting distinct treatment response and clinical outcomes. An understanding of heterogeneous phenotypes of aneuploid CD31- circulating tumor cells (CTCs) and CD31+ circulating tumor endothelial cells (CTECs) may provide novel insights in the clinical management of SCLC. In the present translational and prospective study, increased cancer metastasis-related cell proliferation and motility, accompanied with up-regulated mesenchymal marker vimentin but down-regulated epithelial marker E-cadherin, were observed in both lentivirus infected SCLC and NSCLC cells overexpressing the stemness marker CD44v6. Aneuploid CTCs and CTECs expressing CD44v6 were longitudinally detected by SE-iFISH in 120 SCLC patients. Positive detection of baseline CD44v6+ CTCs and CD44v6+ CTECs was significantly associated with enhanced hepatic metastasis. Karyotype analysis revealed that chromosome 8 (Chr8) in CD44v6+ CTCs shifted from trisomy 8 towards multiploidy in post-therapeutic patients compared to pre-treatment subjects. Furthermore, the burden of baseline CD44v6+ CTCs (t0) or amid the therapy (t1-2), the ratio of baseline CD31+ CTEC/CD31- CTC (t0), and CTC-WBC clusters (t0) were correlated with treatment response and distant metastases, particularly brain metastasis, in subjects with limited disease (LD-SCLC) but not in those with extensive disease (ED-SCLC). Multivariate survival analysis validated that longitudinally detected CD44v6+/CD31- CTCs was an independent prognostic factor for inferior survival in SCLC patients. Our study provides evidence for the first time that comprehensive analyses of CTCs, CTECs, and their respective CD44v6+ subtypes enable clinical stratification and improve prognostic prediction of SCLC, particularly for potentially curable LD-SCLC.

Amine-Free, Directing-Group-Free and Redox-Neutral α-Alkylation of Saturated Cyclic Ketones.

The activation of the α-C-H bond of ketones typically requires an amine and a directing group to guide the reaction selectivity in amine-catalysis carbonyl chemistry. For an α-C-H bond activation of ketone, directing groups are also required to control the reaction selectivity. Reported herein is the first α-alkylation of cyclic ketones in the absence of an amine catalyst and directing group. 1 H NMR, XPS, EPR studies and DFT calculations indicate that an α-carbon radical intermediate is formed through direct and selective activation of the inert α-C-H bond of ketones chelating on the surface of colloidal quantum dots (QDs). Such an interaction is essential for weakening the C-H bond, as exemplified, using CdSe QDs as the sole photocatalyst to execute α-C-H alkylation of cyclic ketones under visible-light irradiation. Without an amine catalyst and directing group, the high step- and atom-economy transformation under redox-neutral condition opens a new way for α-C-H functionalization of ketones in carbonyl chemistry.

[Microplastics pollution in the Yellow River basin: current status and control strategy].

Microplastics pollution has attracted worldwide attention. Compared with the status quo of microplastics pollution in marine environment and other major rivers and lakes, the relevant data of the Yellow River basin is relatively inadequate. The abundance, types, and spatial distribution characteristics of microplastic pollution in the sediments and surface water of the Yellow River basin were reviewed. Meanwhile, the status of microplastic pollution in the national central city and Yellow River Delta wetland was discussed, and the corresponding prevention and control measures were put forward. The results showed that the spatial distribution of microplastics pollution in sediments and surface water of the Yellow River basin increased from upstream to downstream, especially in the Yellow River Delta wetland. There are obvious differences between the types of microplastics in sediment and surface water in the Yellow River basin, which is mainly related to the materials of microplastics. Compared with similar regions in China, the microplastics pollution levels in national key cities and national wetland parks in the Yellow River basin are in the medium to high degree, which should be taken seriously. Plastics exposure through various ways will cause serious impact on aquaculture and human health in the Yellow River beach area. To control microplastic pollution in the Yellow River basin, it is necessary to improve the relevant production standards, laws and regulations, and improve the capacity of biodegradable microplastics and the degradation capacity of plastic wastes.

Properties of flavonoids in the treatment of bladder cancer (Review).

Given its high recurrence and rapid progress, bladder cancer (BLCA) treatment has become a major problem for clinicians. BLCA is difficult to control even with surgical resection and extensive use of chemotherapeutic drugs. The non-toxicity and ease of accessibility of natural compounds have attracted much attention in recent years. Flavonoids serve an essential role given their antioxidant, antibacterial, anticancer and cardiovascular properties. They are mainly divided into several subclasses; flavones, flavanones, flavonols, flavanols, anthocyanins isoflavones and chalcones. Over the years, the role of flavonoids in BLCA has been extensively studied. The present review provided a comprehensive overview of the classification of flavonoids and substantiate the role of epithelial-mesenchymal transition, cancer stem cells, angiogenesis, epigenetic regulation and programmed cell death in BLCA. The present review emphasized that flavonoids for BLCA treatment are worthy of further study and anti-BLCA drugs have huge prospects for clinical use.

Non-pharmacological intervention effects on apathy caused by central nervous system organic diseases: A network meta-analysis.

BACKGROUND: To evaluate the best non-pharmacological interventions on apathy in patients with central nervous system (CNS) organic diseases. METHODS: We searched PubMed, Web of Science, Embase, Cochrane Library electronic databases, China national knowledge infrastructure, Wanfang and Chinese biomedical literature database studies published from 2011 to May 29, 2021. A combination of subject words and free words were used for searching. Randomized controlled trials (RCTs) of non-pharmacological interventions for apathy in patients with central nervous organic disease were included. Two researchers independently identified the eligible RCTs and extracted information. The risk of bias within each individual trial was assessed using the Cocharane Collaboration's tool. Review Manager 5.4 and ADDIS 1.16.5 were used for data analysis. RESULTS: A total of 5324 related studies were obtained in the initial screening, and final 8 RCTs including 334 patients were included, involving 4 non-pharmacological interventions of cognitive intervention, repetitive transcranial magnetic stimulation (rTMS), music therapy and occupational therapy. Direct comparison results showed that rTMS, cognitive intervention, and occupational therapy were superior to the conventional group (P < .05). Network Meta repeated rTMS, cognitive intervention was superior to the conventional group (P < .05), while the other groups did not differ from with the conventional group (P > .05). The order of superiority was rTMS, cognitive intervention, occupational therapy, music therapy, and conventional group. CONCLUSION: Current evidence suggests that rTMS and cognitive interventions are more effective than the conventional intervention in improving apathy in patients with CNS organic diseases. It still needs more non-pharmacological intervention studies with high quality, larger sample sizes for further exploration.

LAMTOR3 is a prognostic biomarker in kidney renal clear cell carcinoma.

OBJECTIVE: The objective of the study was to investigate the expression of LAMTOR3 in kidney renal clear cell carcinoma (KIRC) and its clinical significance. METHODS: The expression of LAMTOR3 in KIRC and its relationship with clinical features were analyzed using the UALCAN online database. The results were verified using KIRC gene chip data and clinical specimens. The prognosis of KIRC patients was analyzed with the GEPIA2 database. GO, KEGG, and GSEA analyses were conducted to analyze the possible molecular mechanism of LAMTOR3 in KIRC. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection. RESULTS: UALCAN database analysis showed that LAMTOR3 expression in KIRC was significantly lower than in normal kidney tissues and correlated with the clinical stage, pathological grade, and tumor genotype (p < .05). GSE53757 dataset analysis consistently showed that the expression of LAMTOR3 in KIRC was significantly lower than in normal kidney tissues (p < .01). GEPIA2 database analysis indicated that patients with low LAMTOR3 expression had poor overall and disease-free survival rates. GSEA analysis suggested that LAMTOR3 positively regulated the citrate cycle and drug metabolism cytochrome P450 and negatively regulated folate biosynthesis and olfactory transduction. The expression of LAMTOR3 in KIRC was also significantly correlated with immune cell infiltration. Finally, IHC showed that LAMTOR3 expression in the KIRC tissues was lower than in the adjacent normal tissues. CONCLUSION: LAMTOR3 expression is significantly lower in KIRC. LAMTOR3 may be a potential marker for KIRC diagnosis and therapy.

Effects of photographer physical attractiveness on photograph aesthetic value assessment.

Existent studies have demonstrated that being physically attractive leads to preferences and rewards in various scenarios involving performance evaluation. In this study, we explored whether a photographer's physical attractiveness could affect others' assessment of a photograph's aesthetic value. Participants (N=54) accomplished an online task to pair portraits and non-portrait photographs, followed by completing two questionnaires on cognitive reflection and empathy. Analytical results revealed that an attractive photographer was more likely to be associated with a highly aesthetic photograph, and this bias was moderated by the participant's level of cognitive reflection and empathy. Meanwhile, it could be reduced by the participant's professional experience.

Direct, Site-Selective and Redox-Neutral α-C-H Bond Functionalization of Tetrahydrofurans via Quantum Dots Photocatalysis.

As one of the most ubiquitous bulk reagents available, the intrinsic chemical inertness of tetrahydrofuran (THF) makes direct and site-selective C(sp3 )-H bond activation difficult, especially under redox neutral condition. Here, we demonstrate that semiconductor quantum dots (QDs) can activate α-C-H bond of THF via forming QDs/THF conjugates. Under visible light irradiation, the resultant alkoxyalkyl radical directly engages in radical cross-coupling with α-amino radical from amino C-H bonds or radical addition with alkene or phenylacetylene, respectively. In contrast to stoichiometric oxidant or hydrogen atom transfer reagents required in previous studies, the scalable benchtop approach can execute α-C-H bond activation of THF only by a QD photocatalyst under redox-neutral condition, thus providing a broad of value added chemicals starting from bulk THFs reagent.

Modeling and prediction for diesel performance based on deep neural network combined with virtual sample.

The performance models are the critical step for condition monitoring and fault diagnosis of diesel engines, and are an important bridge to describe the link between input parameters and targets. Large-scale experimental methods with higher economic costs are often adopted to construct accurate performance models. To ensure the accuracy of the model and reduce the cost of the test, a novel method for modeling the performances of marine diesel engine is proposed based on deep neural network method coupled with virtual sample generation technology. Firstly, according to the practical experience, the four parameters including speed, power, lubricating oil temperature and pressure are selected as the input factors for establishing the performance models. Besides, brake specific fuel consumption, vibration and noise are adopted to assess the status of marine diesel engine. Secondly, small sample experiments for diesel engine are performed under multiple working conditions. Moreover, the experimental sample data are diffused for obtaining valid extended data based on virtual sample generation technology. Then, the performance models are established using the deep neural network method, in which the diffusion data set is adopted to reduce the cost of testing. Finally, the accuracy of the developed model is verified through experiment, and the parametric effects on performances are discussed. The results indicate that the overall prediction accuracy is more than 93%. Moreover, power is the key factor affecting brake specific fuel consumption with a weighting of 30% of the four input factors. While speed is the key factor affecting vibration and noise with a weighting of 30% and 30.5%, respectively.

Eddy covariance measurements of ozone flux above and below a southern subtropical forest canopy.

While extensive eddy covariance (EC) measurements of ozone (O3) flux have been reported in American and European forests, such measurements in Asian forests are scarce. Here, we presented the first EC measurements of O3 flux at two levels (above and below the canopy) in a Chinese forest. Above the canopy, O3 always moved downward, with a maximum O3 flux intensity of -15 ~ -10 nmol m-2 s-1 occurring at 9:00-14:00 LT and a maximum O3 deposition velocity of 1.23 cm s-1 occurring at 9:00 LT; both of these values fell to nearly 0 at night. The O3 deposition flux and O3 deposition velocity below the canopy were both lower than those above the canopy. This discrepancy reached the maximum at 9:00-15:00 local time (LT), with the O3 deposition flux and O3 deposition velocity below the canopy being approximately 35 and 42% of those above the canopy, respectively. The O3 flux was well correlated with the CO2 flux and the latent heat flux, suggesting the important role of stomatal uptake in O3 deposition. The O3 deposition velocity increased with the increase in the air temperature, relative humidity, photosynthetically active radiation and friction velocity, but when these meteorological factors exceeded their optimum values, the increase in the O3 deposition velocity tended to be flat. These findings advanced our understanding of the interactions between forests and the atmosphere. This unique dataset is also of great significance for the validation of relevant models concerned with the various impacts of the rapid increase in global O3 concentrations.