Ligand-Enabled Palladium-Catalyzed [3 + 2] Annulation of Aryl Iodides with Maleimides via C(sp3)-H Activation.

Palladium-catalyzed intermolecular [3 + 2] annulation reactions via C-H activation represent a powerful and charming tool for assembling cyclopentanes. Herein, we have developed a strategy for the palladium-catalyzed intermolecular alkene-relayed annulation reaction of aryl iodides and maleimides via C(sp3)-H activation for the construction of polycyclic structures. In contrast to directed-group-enabled intermolecular maleimide-relayed [3 + 2] annulation reactions, this protocol stands out for its utilization of aryl iodides as substrates. Notably, monoprotected amino acids played a crucial role as ligands in this reaction, which is rarely observed in C-H activation reactions initiated with organohalides.

Rh-Catalyzed Carbonylative Cyclization of Propargylic Alcohols with Aryl Boronic Acids.

2(3H)-Furanones are tremendously important not only because of their wide occurrence in bioactive compounds but also due to their versatility in organic synthesis. Here, a straightforward approach to 2(3H)-furanones from readily available tertiary propargylic alcohols with arylboronic acids in the presence of CO using rhodium as a catalyst has been established. The method exhibits a broad substrate scope tolerating useful functional groups with a moderate to high stereoselectivity.

Pathogenicity studies and molecular characterization of DPV infection in ducklings.

In the spring of 2023, 10 to 21-day-old chicks in a broiler duck farm in Shandong Province, China, developed swelling of the head and neck, moist eyes with mucous discharge, difficulty in walking, shrinking of the neck, and loose and disorganized coat. Anatomical observation revealed hemorrhages in the esophageal mucosa, myocardium, and liver, and severe hemorrhages in the trachea with copious inflammatory secretions. Soon after, similar symptoms appeared in a large number of ducks in the flock, which eventually led to the elimination of all the 20,000-odd newly introduced ducklings on the farm, resulting in huge economic losses. We detected duck plague virus in the tissues of liver, spleen and lungs of diseased and dead ducks, and successfully isolated the pathogenic strain, named SD423, by inoculating duck embryos and inoculating duck embryo fibroblasts. We successfully conducted animal regression experiments with the isolated strain, and the experimental animals in the 1 d of age group showed symptoms of swollen eyes and tearing, shrinking of the neck, crouching, and hemorrhage in organs such as the liver and intestines successively from the 3rd d. We sequenced the whole genome of the isolated duck plague strain, and by comparing the homology with the published duck plague virus whole sequences in Genbank, the virus strain obtained in this study had the highest homology with the Chinese virulent strain SD (MN518864.1), with nucleotide (nt) homology of about 99.90% and amino acid (aa) homology of about 99.75%, which indicated that the isolate is a virulent strain. Previously, it was reported that the natural infection of duck plague virus mainly occurs above 30 d of age, but the duck plague virus found in this study can naturally infect ducklings up to 20 d of age, and the mortality rate is as high as 100%. In this study, the pathogenicity test and whole genome sequence analysis of this isolate provided data support and theoretical basis for further research on pathogenicity and virulence-related gene analysis of duck plague virus.

Macroscopic and microscopic analysis of the effects of moisture content and dry density on the strength of loess.

To clarify the impact of moisture content and dry density on the strength of loess, the remolded loess samples with different moisture content and dry density were prepared, and the influence of moisture content and dry density on loess strength was explored from the macro level by direct shear test without suction control. On this basis, the mechanism of the influence of moisture content and dry density on loess strength was explored from the micro level by nuclear magnetic resonance method. The research results indicate that: In the case of low water content, there are peak points in the stress-strain curve of remolded loess, exhibiting strain softening characteristics. In the case of high water content, there is no obvious peak in the stress-strain curve, exhibiting strain hardening characteristics. Moisture has a significant impact on the shear strength of remolded loess. As the moisture content of the soil sample increases, the cohesion decreases significantly, and the change in internal friction angle is not obvious. As the moisture content continues to increase, the free water content continues to increase. Free water will continuously soften the soil particle structure, reduce the bonding force between soil particles, and cause the cohesion to decrease with the increase of moisture content. The change in dry density also has a significant impact on the shear strength parameters of remolded loess. As the dry density of the soil sample increases, the cohesion increases. The smaller the dry density, the larger the pore ratio, and the looser the contact between soil particles, weakening the bonding effect. The larger the pore ratio, the more bound water is converted to free water, and the strong bonding force between the water film and soil particles disappears. Both of these microscopic factors can lead to a decrease in cohesion with a decrease in dry density.

Efficacy of Astragalus membranaceus-Carthamus tinctorius in cerebral ischemia/reperfusion injury: Insights from metabolomics and mass spectrometry imaging.

BACKGROUND: The combination of Astragalus membranaceus and Carthamus tinctorius (AC) exhibits significant therapeutic effects in cerebral ischemia/reperfusion injury (CIRI). Understanding the metabolic characteristics of brain microregions and disturbances in tissues and systemic circulation is crucial for elucidating the mechanisms of CIRI and the therapeutic benefits of AC. However, in situ metabolic regulation of the complex brain structure has not been adequately studied, and the therapeutic mechanism of AC requires immediate clarification. PURPOSE: The present study aimed to unveil the specific metabolic reprogramming of CIRI at systemic and microregional levels, identify key metabolic pathways and metabolites, and elucidate the therapeutic mechanisms of AC. METHODS: Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a newly developed technique, was used to investigate metabolites in brain microregions. Hematoxylin-eosin, Nissl, and immunofluorescence staining were performed to visualize the microscopic changes associated with spatial metabolism. A comprehensive metabolomics study was conducted on serum, brain tissue, and microregions, along with neurological assessments, cerebral infarction measurements, and Evans blue experiments, to assess the systemic and local metabolic effects of AC treatment for CIRI. RESULTS: AC significantly reduced neurological damage, minimized infarct size, and repaired blood-brain barrier damage in CIRI rats. AFADESI-MSI demonstrated that the metabolic imbalance caused by CIRI primarily occurs in the cerebral cortex, hippocampus, caudate putamen, thalamus, cerebellar cortex, and fiber tract regions. Significant changes in 16 metabolites were observed in these regions, corresponding to neuron damage, glial cell activation, and neural repair. 20 metabolites from serum and 4 from brain tissue varied significantly with the sham group. Comprehensive metabolomics analysis indicated a close relationship among serum, tissue, and microregional metabolism. CIRI-induced systemic and localized metabolic disorders involve 14 metabolic pathways. AC conferred therapeutic benefits in CIRI by reversing various metabolic imbalances. CONCLUSION: AFADESI-MSI efficiently visualized brain microregion metabolism. Comprehensive metabolomics analysis revealed detailed insights into the specific metabolic reprogramming in CIRI and the therapeutic impacts of AC. AC demonstrated significant clinical potential as an adjunct therapy to existing CIRI treatments.

Refined Cumulative Risk Assessment of Pb, Cd, and as in TCM Decoction Based on Bioavailability through In Vitro Digestion/MDCK Cells.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32-72.49% and 4.98-51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were <1, indicating acceptable health risks. Collectively, our innovation on cumulative risk assessment of TCM and TCM decoction provides a novel strategy with the main purpose of improving population health.

Comprehensive analysis of clinical data and radiomic features from contrast enhanced CT for differentiating benign and malignant pancreatic intraductal papillary mucinous neoplasms.

The primary aim of this investigation was to leverage radiomics features derived from contrast-enhanced abdominal computed tomography (CT) scans to devise a predictive model to discern the benign and malignant nature of intraductal papillary mucinous neoplasms (IPMNs). Radiomic signatures were meticulously crafted to delineate benign from malignant IPMNs by extracting pertinent features from contrast-enhanced CT images within a designated training cohort (n = 84). Subsequent validation was conducted with data from an independent test cohort (n = 37). The discriminative ability of the model was quantitatively evaluated through receiver operating characteristic (ROC) curve analysis, with the integration of carefully selected clinical features to improve the comparative analysis. Arterial-phase images were utilized to construct a model comprising 8 features for distinguishing between benign and malignant cases. The model achieved an accuracy of 0.891 [95% confidence interval (95% CI), 0.816-0.996] in the cross-validation set and 0.553 (95% CI 0.360-0.745) in the test set. Conversely, employing 9 features from the venous-phase resulted in a model with a cross-validation accuracy of 0.862 (95%CI 0.777-0.946) and a test set accuracy of 0.801 (95% CI 0.653-0.950).Integrating the identified clinical features with imaging features yielded a model with a cross-validation accuracy of 0.934 (95% CI 0.879-0.990) and a test set accuracy of 0.904 (95% CI 0.808-0.999), thereby further improving its discriminatory ability. Our findings distinctly illustrate that venous-phase radiomics features eclipse arterial-phase radiomic features in terms of predictive accuracy regarding the nature of IPMNs. Furthermore, the synthesis and meticulous screening of clinical features with radiomic data significantly increased the diagnostic efficacy of our model, underscoring the pivotal importance of a comprehensive and integrated approach for accurate risk stratification in IPMN management.

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography.

BACKGROUND: The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. MATERIALS AND METHODS: This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression. RESULTS: A total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: ß = 0.116; positive remodelling: ß = 0.138; spotty calcification: ß = 0.091; NOS: ß = 0.427; OS: ß = 0.659: SIS: ß = 1.114; SSS: ß = 2.987; PID: ß = 2.716, all P value < 0.001). CONCLUSIONS: Abnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

A novel bioaccessibility-based probabilistic risks assessment of potentially toxic elements (PTEs) in earthworm.

Introduction: Early risk assessment studies usually based on total heavy metal (loid) contents, inevitably leading to an overestimation of the health risks. In addition, inputs are represented as single-point estimates in deterministic models, leading to underestimation or overestimation of the health risks. Methods: To overcome these barriers, a novel probabilistic risk assessment strategy based on the combinational use of bioaccessibility and Monte Carlo simulation was developed to assess heavy metal (loid) associated health risks of earthworms in this study. To obtain a realistic and robust probabilistic risk assessment, heavy metal (loid) exposure duration and frequency were determined using our questionnaire data. Results: As a result, the mean gastrointestinal bioaccessibility was in the order: Cd > As > Cu > Hg. The mean hazard index (HI) values for investigated metal (loid)s were 0.65 and 0.59 for male and female, respectively, demonstrating an acceptable health risk in an average community. However, the 90th percentile of HI values was 1.87 and 1.65 for male and female, respectively. And the total non-cancer risks of heavy metal (loid) exposure exceeded the acceptable threshold for 19.9% and 17.8% of male and female, respectively. In addition, the total cancer risk (TCR) value through co-exposure to As and Cd suggested that the carcinogenic risks may be of concern for average exposure population. Sensitivity analyses revealed that the exposure frequency and bioaccessible As concentration were the dominant contributors to the total risk variance, which provided meaningful implications for environmental management. Conclusion: Altogether, the refined strategy based on bioaccessibility and Monte Carlo simulation is the first of its kind, such effort attempts to scientifically guide the rational clinic use of TCM and the improvement of population-health.

Mechanism of immune activation mediated by genomic instability and its implication in radiotherapy combined with immune checkpoint inhibitors.

Various genetic and epigenetic changes associated with genomic instability (GI), including DNA damage repair defects, chromosomal instability, and mitochondrial GI, contribute to development and progression of cancer. These alterations not only result in DNA leakage into the cytoplasm, either directly or through micronuclei, but also trigger downstream inflammatory signals, such as the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Apart from directly inducing DNA damage to eliminate cancer cells, radiotherapy (RT) exerts its antitumor effects through intracellular DNA damage sensing mechanisms, leading to the activation of downstream inflammatory signaling pathways. This not only enables local tumor control but also reshapes the immune microenvironment, triggering systemic immune responses. The combination of RT and immunotherapy has emerged as a promising approach to increase the probability of abscopal effects, where distant tumors respond to treatment due to the systemic immunomodulatory effects. This review emphasizes the importance of GI in cancer biology and elucidates the mechanisms by which RT induces GI remodeling of the immune microenvironment. By elucidating the mechanisms of GI and RT-induced immune responses, we aim to emphasize the crucial importance of this approach in modern oncology. Understanding the impact of GI on tumor biological behavior and therapeutic response, as well as the possibility of activating systemic anti-tumor immunity through RT, will pave the way for the development of new treatment strategies and improve prognosis for patients.

Development of High-Precision NO2 Gas Sensor Based on Non-Dispersive Infrared Technology.

Increasing concerns about air quality due to fossil fuel combustion, especially nitrogen oxides (NOx) from marine and diesel engines, necessitate advanced monitoring systems due to the significant health and environmental impacts of nitrogen dioxide (NO2). In this study, a gas detection system based on the principle of the non-dispersive infrared (NDIR) technique is proposed. Firstly, the pyroelectric detector was developed by employing an ultra-thin LiTaO3 (LT) layer as the sensitive element, integrated with nanoscale carbon material prepared by wafer-level graphics technology as the infrared absorption layer. Then, the sensor was hermetically sealed using inert gas through energy storage welding technology, exhibiting a high detectivity (D*) value of 4.19 × 108 cm·âˆšHz/W. Subsequently, a NO2 gas sensor was engineered based on the NDIR principle employing a Micro Electro Mechanical System (MEMS) infrared (IR) emitter, featuring a light path chamber length of 1.5 m, along with integrated signal processing and software calibration algorithms. This gas sensor was capable of detecting NO2 concentrations within the range of 0-500 ppm. Initial tests indicated that the gas sensor exhibited a full-scale relative error of less than 0.46%, a limit of 2.8 ppm, a linearity of -1.09%, a repeatability of 0.47% at a concentration of 500 ppm, and a stability of 2% at a concentration of 500 ppm. The developed gas sensor demonstrated significant potential for application in areas such as industrial monitoring and analytical instrumentation.

Corrigendum: Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

[This corrects the article DOI: 10.3389/fimmu.2024.1302903.].

Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK1 receptors.

Chronic primary pain (CPP) occurs in the absence of tissue injury and includes temporomandibular disorders (TMD), fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS). CPP is commonly considered a stress-related chronic pain and often presents as wide-spread pain or comorbid pain conditions in different regions of the body. However, whether prolonged stress can directly result in the development of CPP comorbidity remains unclear. In the present study, we adapted a 21 day heterotypic stress paradigm in mice and examined whether chronic stress induced wide-spread hyperalgesia, modeling comorbid CPP in the clinic. We found that chronic stress induced anxiety- and depression-like behaviors, and resulted in long-lasting wide-spread hyperalgesia over several body regions such as the orofacial area, hindpaw, thigh, upper back and abdomen in female mice. We further found that the expression of cholecystokinin (CCK)1 receptors was significantly increased in the L4-L5 spinal dorsal horn of the female mice after 14 and 21 day heterotypic stress compared with the control animals. Intrathecal injection of the CCK1 receptor antagonist CR-1505 blocked pain hypersensitivity in the subcervical body including the upper back, thigh, hindpaw and abdomen. These findings suggest that the upregulation of spinal CCK1 receptors after chronic stress contributes to the central mechanisms underlying the development of wide-spread hyperalgesia, and may provide a potential and novel central target for clinical treatment of CPP.

A Comprehensive Analysis of Fel Ursi and Its Common Adulterants Based on UHPLC-QTOF-MSE and Chemometrics.

BACKGROUND: As one of the four most valuable animal medicines, Fel Ursi, named Xiong Dan (XD) in China, has the effect of clearing heat, calming the liver, and brightening the eyes. However, due to the special source of XD and its high price, other animals' bile is often sold as XD or mixed with XD on the market, seriously affecting its clinical efficacy and consumers' rights and interests. In order to realize identification and adulteration analysis of XD, UHPLC-QTOF-MSE and multivariate statistical analysis were used to explore the differences in XD and six other animals' bile. METHODS: XD, pig gall (Zhu Dan, ZD), cow gall (Niu Dan, ND), rabbit gallbladder (Tu Dan, TD), duck gall (Yan Dan, YD), sheep gall (Yang Dan, YND), and chicken gall (Ji Dan, JD) were analyzed by UHPLC-QTOF-MSE, and the MS data, combined with multivariate analysis methods, were used to distinguish between them. Meanwhile, the potential chemical composition markers that contribute to their differences were further explored. RESULTS: The results showed that XD and six other animals' bile can be distinguished from each other obviously, with 27 ions with VIP > 1.0. We preliminarily identified 10 different bile acid-like components in XD and the other animals' bile with significant differences (p < 0.01) and VIP > 1.0, such as tauroursodeoxycholic acid, Glycohyodeoxycholic acid, and Glycodeoxycholic acid. CONCLUSIONS: The developed method was efficient and rapid in accurately distinguishing between XD and six other animals' bile. Based on the obtained chemical composition markers, it is beneficial to strengthen quality control for bile medicines.

Palladium-Catalyzed Cascade Carbonylation Reaction: Synthesis of Fused Isoindolinones.

A palladium-catalyzed cascade carbonylation reaction of 2-bromo-N-(2-iodophenyl)benzamides with benzylidenecyclopropanes for the synthesis of fused isoindolinone derivatives has been developed. A broad range of 6/5/6/6 tetracyclic isoindolinone products were efficiently prepared in moderate to good yields with diverse substitution. Two carbonyl groups were incorporated into the substrates in a single step with the formation of four carbon-carbon bonds and two carbon-heteroatom bonds.

Phenolic Constituents with Glucose Uptake and GLUT4 Translocation Bioactivities from the Fruits of Cordia dichotoma.

From the fruits of Cordia dichotoma, 11 new phenolic compounds, dichotomins A-K, were isolated, together with 19 known compounds. Through the analysis of detailed NMR data and HRESIMS data, the planar structures of all compounds were confirmed. Using NMR calculations, the absolute configuration of dichotomins A-K was elucidated by comparing their observed and computed electronic circular dichroism (ECD) spectra. Dichotomin H (8) and dichotomin I (9) were determined as two pairs of enantiomers. The enantiomers of compounds 8 and 9 were separated using chiral-phase high-performance liquid chromatography (HPLC), and the stereostructure of each enantiomer was determined by similarly calculating the ECD. Compounds 3, 5, 7, 17, 18, 23-25, and 27-30 increased glucose uptake by 1.04- to 2.85-folds at concentrations of 30 µg/mL. Further studies revealed that compounds 3 and 5 had a moderate effect on glucose transporter 4 (GLUT4) translocation activity in L6 cells. At 30 µg/mL, compound 3 significantly enhanced AMPK phosphorylation and GLUT4 expression. As a whole, compound 3 has the potential to be a drug candidate for the treatment of type 2 diabetes mellitus (T2DM).

Dynamic immunoediting by macrophages in homologous recombination deficiency-stratified pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.

Origin recognition complex 6 overexpression promotes growth of glioma cells.

The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 (origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2, Cyclin B2, and DNA topoisomerase II (TOP2A), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6. RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.

[Material basis of kidney Yang deficiency rats before and after salt processing of Dipsacus asper based on spectrum-effect relationship].

This paper aims to study the spectrum-effect relationship between the fingerprints before and after salt processing of Dipsacus asper and the efficacy of warming and tonifying kidney Yang and find the main active components against kidney Yang deficiency before and after salt processing of D. asper, so as to provide the basis for clarifying the effect of salt processing on kidney Yang deficiency. The HPLC fingerprint before and after salt processing of D. asper was established by the HPLC-DAD. 15 common peaks were obtained, and 11 components were identified. The content changes of various components in rat serum were detected, and the difference in efficacy before and after salt processing was compared. The results of pharmacological experiments showed that salt processing of D. asper could enhance the kidney index. At the same dose, there was a significant difference between the raw D. asper and D. asper after salt processing groups. Compared with the model group, the contents of ACTH, cAMP, CORT, E_2, GH, Na~+-K~+-ATPase, T, and T4 in the serum of rats in the administration group increased to a certain extent, and the contents of cGMP and TNF-α decreased to a certain extent. Among them, there were significant differences in the above indexes in the serum of rats in the high-dose group of raw D. asper, middle-dose group of D. asper after salt processing, high-dose group of D. asper after salt processing, and the positive drug group. The overall results showed that D. asper after salt processing was more effective than raw D. asper in preventing kidney yang deficiency. The efficacy of D. asper was evaluated by grey correlation analysis, entropy method, and Pearson correlation analysis, and the components of D. asper after salt processing against kidney yang deficiency were screened out. According to the results of correlation degree ranking, the components with increased ranking before and after salt processing of D. asper were loganin, chlorogenic acid, dipsacoside A, asperosaponin Ⅵ, caffeic acid, and isochlorogenic acid B. It was preliminarily speculated that these compounds may be the potential pharmacodynamic components for the treatment of kidney yang deficiency before and after salt processing of D. asper. The changing components before and after the salt processing of D. asper were determined, which proved that D. asper after salt processing was superior to D. asper in the treatment of kidney yang deficiency. The spectrum-effect relationship between the efficacy of D. asper before and after salt processing and the treatment of kidney yang deficiency was established, which laid a foundation for the subsequent study on the pharmacodynamic components and molecular mechanism of salt processing of D. asper.

[Effects of " Air Pollution Prevention and Control Action Plan " on PM2.5 and Chemical Compositions in Zhengzhou in Polluted Winters].

The Air Pollution Prevention and Control Action Plan （APPCAP） was promulgated in China in 2013. To explore the effectiveness of APPCAP on PM2.5 in winter in Zhengzhou, PM2.5 samples were collected in Zhengzhou Monitoring Center during December 2013 and December 2018. The chemical composition of PM2.5 was analyzed, including EC, OC, water soluble ions, and metal elements. Pollution episodes under different stages were selected to investigate the changes in PM2.5 concentration and composition. The results showed that： ① The average concentration of PM2.5 in winter in Zhengzhou decreased from （215.38 ±107.28） µg·m-3 in 2013 to （77.45 ±49.81） µg·m-3 in 2018, with a decrease rate of 64%. ② The concentrations of EC, K+, SO42-, and Cl- decreased by 85%, 80%, 78%, and 72%, respectively, and the decrease rate in OC, NH4+, and NO3- was 50%, 41%, and 32%, respectively. ③ Compared with those in winter of 2013, the ratios of OC/EC in winter of 2018 increased by 2.6 times, and the proportion of secondary organic carbon in OC increased to 57%； meanwhile, values of sulfur oxidation rate and nitrogen oxidation rate increased by 1.5 and 1.0 times, respectively, indicating heavy secondary pollution in Zhengzhou. ④ The mass ratios of NO3-/SO42-increased from 0.8 ±0.2 in 2013 to 2.5 ±1.0 in 2018, indicating that the contribution of mobile sources increased and surpassed fixed sources as the main source in Zhengzhou. ⑤The comparison results of different stages of the heavy pollution process showed that ρ（PM2.5） decreased significantly in 2018 compared with that in 2013, with the peak concentration decreasing by 61%. The main chemical composition changed from OC, NO3-, SO42-, and NH4+ to OC, NO3-, and NH4+. The results indicated that the primary emission source control in Zhengzhou had achieved remarkable effects, but the contribution of secondary generation to PM2.5 showed an elevated trend； thus, the influence of secondary generation requires further attention in the future.