Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Development and Validation of a Nomogram for Predicting Nutritional Risk Based on Frailty Scores in Older Stroke Patients.

BACKGROUND: In older stroke patients with frailty, nutritional deficiencies can amplify their susceptibility, delay recovery, and deteriorate prognosis. A precise predictive model is crucial to assess their nutritional risk, enabling targeted interventions for improved clinical outcomes. OBJECTIVE: To develop and externally validate a nutritional risk prediction model integrating general demographics, physical parameters, psychological indicators, and biochemical markers. The aim is to facilitate the early identification of older stroke patients requiring nutritional intervention. METHODS: This was a multicenter cross-sectional study. A total of 570 stroke patients were included, 434 as the modeling set and 136 as the external validation set. The least absolute shrinkage selection operator (LASSO) regression analysis was used to select the predictor variables. Internal validation was performed using Bootstrap resampling (1000 iterations). The nomogram was constructed based on the results of logistic regression. The performance assessment relied on the receiver operating characteristic curve (ROC), Hosmer--Lemeshow test, calibration curves, Brier score, and decision curve analysis (DCA). RESULTS: The predictive nomogram encompassed seven pivotal variables: Activities of Daily Living (ADL), NIHSS score, diabetes, Body Mass Index (BMI), grip strength, serum albumin levels, and depression. Together, these variables comprehensively evaluate the overall health and nutritional status of elderly stroke patients, facilitating accurate assessment of their nutritional risk. The model exhibited excellent accuracy in both the development and external validation sets, evidenced by AUC values of 0.934 and 0.887, respectively. Such performance highlights its efficacy in pinpointing elderly stroke patients who require nutritional intervention. Moreover, the model showed robust goodness of fit and practical applicability, providing essential clinical insights to improve recovery and prognosis for patients prone to malnutrition. CONCLUSIONS: Elderly individuals recovering from stroke often experience significant nutritional deficiencies. The nomogram we devised accurately assesses this risk by combining physiological, psychological, and biochemical metrics. It equips healthcare providers with the means to actively screen for and manage the nutritional care of these patients. This tool is instrumental in swiftly identifying those in urgent need of targeted nutritional support, which is essential for optimizing their recovery and managing their nutrition more effectively.

Covalent Organic Frameworks: Linkage Chemistry and Its Critical Role in The Evolution of π Electronic Structures and Functions.

Covalent organic frameworks (COFs) provide a molecular platform for designing a novel class of functional materials with well-defined structures. A crucial structural parameter is the linkage, which dictates how knot and linker units are connected to form two-dimensional polymers and layer frameworks, shaping ordered π-array and porous architectures. However, the roles of linkage in the development of ordered π electronic structures and functions remain fundamental yet unresolved issues. Here we report the designed synthesis of COFs featuring four representative linkages: hydrazone, imine, azine, and C=C bonds, to elucidate their impacts on the evolution of π electronic structures and functions. Our observations revealed that the hydrazone linkage provides a non-conjugated connection, while imine and azine allow partial π conjugation, and the C=C bond permits full π-conjugation. Importantly, the linkage profoundly influences the control of π electronic structures and functions, unraveling its pivotal role in determining key electronic properties such as band gap, frontier energy levels, light absorption, luminescence, carrier density and mobility, and magnetic permeability. These findings highlight the significance of linkage chemistry in COFs and offer a general and transformative guidance for designing framework materials to achieve electronic functions.

Molecular regulatory mechanisms of erythropoiesis and related diseases.

The metabolism of cells and blood circulation allow for the constant production and destruction of red blood cells. Erythrocyte formation allows red blood cells to regenerate, which is crucial for maintaining the equilibrium of the organism. Erythrocyte formation is a multi-step, intricate process with distinct structural and functional characteristics at each stage. Erythropoiesis is regulated by a number of signaling pathways; malfunctional regulatory mechanisms may result in disease and aberrant erythropoiesis. Therefore, this article focuses on a review of the erythroid formation process, related signaling pathways, and red blood cell lineage diseases.

Baicalin inhibits hepatocellular carcinoma cell growth and metastasis by suppressing ROCK1 signaling.

Hepatocellular carcinoma (HCC) is a common malignancy affecting many people worldwide. Baicalin is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi. It can effectively inhibit the occurrence and development of HCC. Nonetheless, the mechanism through which Baicalin inhibits HCC growth and metastasis remain unknown. This work discovered that Baicalin inhibited HCC cell proliferation, invasion, metastasis while inducing cell cycle arrest at the G0/G1 phase and apoptosis. In vivo HCC xenograft results indicated that Baicalin inhibited HCC growth. Western blotting analysis indicated that Baicalin suppressed the expressions of ROCK1, p-GSK-3ß, and ß-catenin, whereas it up-regulated the expressions of GSK-3ß and p-ß-catenin. Baicalin also reduced the expressions of Bcl-2, C-myc, Cyclin D1, MMP-9, and VEGFA, while increasing the expression of Bax. Molecular docking revealed that Baicalin docked in the binding site of the ROCK1 agonist, with a binding energy of -9 kcal/mol between the two. In addition, lentivirus-mediated suppression of ROCK1 expression improved the inhibitory effect of Baicalin on the proliferation, invasion, and metastasis of HCC and the expression of proteins associated with ROCK1/GSK-3ß/ß-catenin signaling pathway. Moreover, restoring ROCK1 expression decreased the anti-HCC efficacy of Baicalin. These findings suggest that Baicalin may decrease HCC proliferation and metastasis by suppressing ROCK1/GSK-3ß/ß-catenin signaling.

Impact of humidity and flowrate on the thoron measurement sensitivity of electrostatic radon monitors.

The accurate measurement of thoron activity concentration is an important issue in both thoron exposure evaluation and in reducing its influence on radon measurement. For radon monitors based on electrostatic collection technique and an alpha spectrometry analyser, air humidity and sampling flowrate are key factors influencing the sensitivity of thoron activity concentration measurement. For the purpose of improving thoron measurement sensitivity and stability, theoretical derivation and experimental studies were systemically performed in this study. The results show that thoron measurement sensitivity decreases as a negative exponential function with absolute humidity increasing, and the sensitivity of thoron is much lower than that of radon under the same conditions, which is mainly caused by the small value of the concentration ratio of thoron inside to outside of the chamber. When the air exchange rate of the measurement chamber (sampling flowrate/inner volume) increases, the measurement sensitivity of thoron gas first increases rapidly and then decreases slowly after reaching its maximum at the air exchange rate of 0.24 s-1. In practice, in the normal air exchange rate range (for example <0.05 s-1), increasing the sampling flowrate could greatly improve the thoron measurement sensitivity, which consequently suggests an effective way to update thoron measurement under the present conditions of the monitor.

Deletion of large-conductance calcium-activated potassium channels promotes vascular remodelling through the CTRP7-mediated PI3K/Akt signaling pathway.

The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture, and abnormal expression or dysfunction of this channel is linked to many vascular diseases. Vascular remodelling is the early pathological basis of severe vascular diseases. Delaying the progression of vascular remodelling can reduce cardiovascular events, but the pathogenesis remains unclear. To clarify the role of BK channels in vascular remodelling, we use rats with BK channel α subunit knockout (BK α ‒/‒). The results show that BK α ‒/‒ rats have smaller inner and outer diameters, thickened aortic walls, increased fibrosis, and disordered elastic fibers of the aortas compared with WT rats. When the expression and function of BK α are inhibited in human umbilical arterial smooth muscle cells (HUASMCs), the expressions of matrix metalloproteinase 2 (MMP2), MMP9, and interleukin-6 are enhanced, while the expressions of smooth muscle cell contractile phenotype proteins are reduced. RNA sequencing, bioinformatics analysis and qPCR verification show that C1q/tumor necrosis factor-related protein 7 ( CTRP7) is the downstream target gene. Furthermore, except for that of MMPs, a similar pattern of IL-6, smooth muscle cell contractile phenotype proteins expression trend is observed after CTRP7 knockdown. Moreover, knockdown of both BK α and CTRP7 in HUASMCs activates PI3K/Akt signaling. Additionally, CTRP7 is expressed in vascular smooth muscle cells (VSMCs), and BK α deficiency activates the PI3K/Akt pathway by reducing CTRP7 level. Therefore, we first show that BK channel deficiency leads to vascular remodelling. The BK channel and CTRP7 may serve as potential targets for the treatment of cardiovascular diseases.

The support dilemma of stroke inpatients and family caregivers under COVID-19 prevention and control: a qualitative study in China.

China has implemented a strict isolation system in hospitals since the COVID-19 pandemic, that adversely affected the psychology of inpatients and their caregivers. Face-to-face, semi-structured interviews with 22 stroke inpatients from two municipal hospitals were conducted to explore the psychological, emotional and related support needs of stroke inpatients and their family caregivers under this environment. Results which showed that external support for stroke inpatients and their family caregivers was insufficient highlight the necessity for developing specific nursing interventions that meet the psychological and emotional needs of inpatients and the caregivers.

Deletion of BK channels decreased skeletal and cardiac muscle function but increased smooth muscle contraction in rats.

Large conductance calcium-activated potassium channel (BK channel) is widely expressed in skeletal muscle, myocardium, smooth muscle and other muscle tissues. Mutation, abnormal expression and altered activity of BK channel are linked to muscle-related diseases such as dyskinesia, epilepsy and erectile dysfunction. In order to compare the effects of BK channel on different muscle tissues, we constructed BK channel gene knockout rats||||||| (BK-/- rats). HE staining, open field and grip strength tests, ultrasound, blood pressure measurement and vascular tension test were utilized to explore the effects of BK channel deletion on the structure and function changes in skeletal muscle, myocardium, and vascular smooth muscle (VSM). It was found that compared with wild-type rats, the BK-/- rats showed decreased skeletal muscle fiber area, grip, movement distance and speed at 2 and 12 months of ages. At heart, the muscle fiber area, cardiac systolic/diastolic function and heart rate decreased in BK-/- rats. The wall of the left ventricle became thin. However, the vascular wall of BK-/- rats thickened, the pulse wave velocity was increased, and the VSM contraction was enhanced. Unexpectedly, both systolic and diastolic blood pressure were reduced in BK-/- rats, while pulse pressure difference was increased. These results suggest that BK channel may have different effects on different types of muscle tissue, and it should be noted that different parts of muscle tissue may have different effects when BK channel-related drugs are used.

Insecticidal and acetylcholine esterase inhibition activity of Rhododendron thymifolium essential oil and its main constituent against two stored product insects.

In this work, we investigated the bioactivities of the essential oil (EO) extracted from the Rhododendron thymifolium and its principal germacrone against Lasioderma serricorne and Tribolium castaneum. The EO was obtained by steam distillation. Germacrone was obtained by cryogenic crystallization. The bioactivity of EO and germacrone was tested via contact and repellent activity assays. The results showed that EO and germacrone possessed contact and repellent activities against two species of insects. EO exhibited obvious contact activity against the L. serricorn adults, larvae and T. castaneum larvae with LD50 values of 29.15 µg/adult, 42.73 µg/larva, 19.65 µg/larva respectively. Germacrone exhibited excellent contact activity against the L. serricorne adults, larvae and the T. castaneum larvae with LD50 values of 17.18 µg/adult, 20.94 µg/larva, 20.93 µg/larva respectively. And at the highest testing concentrations (78.63 and 15.73 nL/cm2), the repellent activity of EO and germacrone on two target insects was comparable to that of the positive control (DEET) after 30 h exposure. In especially, in the treatment of the 120 h after the repellent activity of EO and germacrone against T.castaneum adults and larvae were still very significant and showed the same level percentage repellency as DEET. Meanwhile, germacrone exhibited inhibition of acetylcholinesterase activity with IC50 values of 3%. The results indicated that the EO of R. thymifolium and germacrone had the potential to be developed as natural insecticides and repellents for the control of T. castaneum and L. serricorne.

Isolation and culture of vascular smooth muscle cells from rat placenta.

We developed a new separation method for isolating placental vascular smooth muscle cells (PVSMCs) from a rat in this study. Our method used the magnetic force between a magnet and ferrous ferric oxide (Fe3 O 4 ) to make the separation and extraction processes easier and more efficient. From the first to sixth generation, the cells isolated using this protocol were identified as smooth muscle cells (SMCs) by their immunoreactivity to the SMC markers and by the "hill and valley" morphology. PVSMCs were exposed to angiotensin II (1 µmol/L) and resulted in sharply increased intracellular Ca 2+ concentration. Furthermore, activation of protein kinase C (PKC) increased concomitantly with a decrease in calponin expression. These results indicate that the isolated cells had biological activity. Our method of isolating PVSMCs from rat leads to isolation of cultured cells with activity and high purity. The approach will be useful in research studies on placental vascular diseases.

Evaluation of riboflavin photochemical treatment for inactivation of HCT116 tumor cells mixed in simulative intraoperative salvage blood.

BACKGROUND: Radiation and filtration have achieved satisfactory results in inactivation or removal of tumor cells mixed in salvage blood, but some drawbacks remain. This study evaluated the inactivation on HCT116 cells mixed in simulative salvage blood by riboflavin photochemical treatment. METHODS: HCT116 cells were added to the whole blood to simulate contaminated salvaged blood. The mixed blood was added with riboflavin of 50 µmol/L final concentration and illuminated by ultraviolet light. The samples were divided into control group and Experimental Groups 1 (18 J/cm2 ), 2 (23.4 J/cm2 ), and 3 (28.8 J/cm2 ). An autotransfusion system (Cell Saver Elite, Haemonetics) was used to simulate the intraoperative blood salvage procedure to deal with whole blood. The apoptosis rate and tumorigenicity of HCT116 cells and the superimposed damage to red blood cells (RBCs) were evaluated. RESULTS: The apoptosis rates of HCT116 in Experimental Groups 1, 2, and 3 were much higher than that in the control group. Tumor growth was found in the control group, but no tumor growth was found in the three experimental groups. The hemolysis rates in the three experimental groups were significantly higher than that in the control group, but much lower than the quality standard of RBCs at the end of preservation. The concentration of adenosine triphosphate in RBCs was comparable in the control and experimental groups. CONCLUSION: Riboflavin at a 50 µmol/L final concentration and 18 J/cm2 ultraviolet illumination can effectively inactivate HCT116 cells in salvaged blood, with minimum damage to the structure and function of RBCs, and the main quality indexes of salvaged RBCs were within the standard range.

New Caffeoylquinic Acid Derivatives and Flavanone Glycoside from the Flowers of Chrysanthemum morifolium and Their Bioactivities.

The Chrysanthemum morifolium flower is widely used in China and Japan as a food, beverage, and medicine for many diseases. In our work, two new caffeoylquinic acid derivatives (1, 2), a new flavanone glycoside (3), and six reported flavanones (4⁻9) were isolated and identified from the flowers of C. morifolium. The chemical structures of all isolates were elucidated by the analysis of comprehensive spectroscopic data as well as by comparison with previously reported data. The isolated constituents 1⁻8 were evaluated for their neuroprotective activity, and compounds 3 and 4 displayed neuroprotective effects against hydrogen peroxide-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.

First-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor alone or with whole-brain radiotherapy for brain metastases in patients with EGFR-mutated lung adenocarcinoma.

We proposed to compare the outcomes of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) alone with EGFR-TKI plus whole-brain radiotherapy (WBRT) for the treatment of brain metastases (BM) in patients with EGFR-mutated lung adenocarcinoma. A total of 1665 patients were screened from 2008 to 2014, and 132 were enrolled in our study. Among the 132 patients, 72 (54.5%) harbored a deletion in exon 19, 97 (73.5%) showed multiple intracranial lesions, and 67 (50.8%) had asymptomatic BM. Seventy-nine patients (59.8%) were treated with EGFR-TKI alone, 53 with concomitant WBRT. The intracranial objective response rate was significantly higher in the EGFR-TKI plus WBRT treatment group (67.9%) compared with the EGFR-TKI alone group (39.2%) (P = 0.001). After a median follow-up of 36.2 months, 62.1% of patients were still alive. The median intracranial TTP was 24.7 months (95% CI, 19.5-29.9) in patients who received WBRT, which was significantly longer than in those who received EGFR-TKI alone, with the median intracranial TTP of 18.2 months (95% CI, 12.5-23.9) (P = 0.004). There was no significant difference in overall survival between WBRT and EGFR-TKI alone groups, (median, 48.0 vs 41.1 months; P = 0.740). The overall survival is significantly prolonged in patients who had an intracranial TTP exceeding 22 months compared to those who developed intracranial progression <22 months after treatment, (median, 58.0 vs 28.0 months; P = 0.001). For EGFR-mutated lung adenocarcinoma patients with BM, treatment with concomitant WBRT achieved a higher response rate of BM and significant improvement in intracranial progression-free survival compared with EGFR-TKI alone.

Impact of the radiotherapy combined with cisplatin plus paclitaxel chemotherapy on the immunologic functions in the patients with esophageal cancer.

To study the impact of radiotherapy combined with cisplatin plus paclitaxel chemotherapy on the immunologic functions in the patients with esophageal cancer, from July 2012 to September 2014, 82 patients of esophageal cancer which were receiving treatment in our hospital chose out for this research. Among them, 42 patients received radiotherapy only, as the control group; while the other 40 patients with concurrent cisplatin plus paclitaxel chemo radiotherapy was taken as the observation group. Then the immunologic functions, toxic and side effects were compared between the two groups as well as the survival rates after 3-year-followup-visit, Th level of the total T cells, Th cells and the ratio of Th cells to Ts cells after receiving treatment all increased significantly compared with prior treatment. And the difference was statistically significant (P<0.05). After the treatment, the level of T cells, Th cells and the ratio of Th cells to Ts cells of the observation group were all significantly lower than the control group, and the difference was statistically significant (P<0.05). While the difference of the ratio of Ts cells to natural killer cells (NK cells) between the two groups were not significant. The toxic and side effects were mainly myelosuppression, decrease leukocyte, esophagit, nausea and vomiting, and it was not statistically significant in the difference between the two groups (P >0.05), the survival rates from the first year to the third year in the observation group were respectively significantly higher than the control group, and the difference was statistically significant (P<0.05). Radiotherapy combined with cisplatin plus paclitaxel chemotherapy could properly increase the immunologic functions in patients with esophageal cancer, benefiting for the survival rate with a good security. Therefore, it was worth promoting.

Expression of basic fibroblast growth factor, CD31, and α-smooth muscle actin and esophageal cancer recurrence after definitive chemoradiation.

There is cumulative evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aims of this study were to analyze the expression of basic fibroblast growth factor (FGF-2), CD31, and α-smooth muscle actin (SMA) in esophageal cancer patients and to establish their significance as indicators of disease recurrence after definitive chemoradiation (CRT). Protein expressions of FGF-2, CD31, and SMA were evaluated by immunohistochemistry and Western blot analysis in 70 patients, 20 with esophageal squamous cell carcinoma (ESCC) and 50 with locally recurrent ESCC after definitive CRT. Twenty matched normal esophageal squamous epithelium were also studied as controls. Esophageal cancer tissues showed positive expression of FGF-2, CD31, and SMA; in contrast, FGF-2 expression was not detected and only little staining for CD31 and SMA was noted in normal epithelium. Protein levels of FGF-2, CD31, and SMA were significantly elevated in recurrent ESCC. Among the patients with locally recurrent disease, expression of FGF-2 and SMA was notably high in whom the tumor recurred locally within 24 months after definitive CRT. The 2- and 5-year local recurrence-free survival rate was 15.4 % and 0 in patients with high FGF-2 expression, compared with 45.8 and 33.3 % in those who expressed low FGF-2, respectively (P = 0.005). Of patients who expressed high SMA, the 2- and 5-year local recurrence-free survival rate was 21.7 and 8.7 %, respectively, compared to those with low SMA expression which was 37.0 and 22.2 %, respectively (P = 0.016). Overexpression of FGF-2 and SMA is associated with local recurrence and reduced recurrence-free survival after definitive CRT for ESCC. The data also suggest that targeting stromal cells may be an attractive approach for esophageal cancer therapy strategies.

Combining microbiome and pseudotargeted metabolomics revealed the alleviative mechanism of Cupriavidus sp. WS2 on the cadmium toxicity in Vicia unijuga A.Br.

Cadmium (Cd) pollution is one of the most severe toxic metals pollution in grassland. Vicia unijuga (V. unijuga) A.Br. planted nearby the grassland farming are facing the risk of high Cd contamination. Here, we investigated the beneficial effects of a highly Cd tolerant rhizosphere bacterium, Cupriavidus sp. WS2, on Cd contaminated V. unijuga. Through plot experiments, we set up four groups of treatments: the control group (without WS2 or Cd), the Cd group (with only Cd addition), the WS2 group (with only WS2 addition), and the WS2/Cd group (with WS2 and Cd addition), and analyzed the changes in physiological indicators, rhizosphere microorganisms, and stem and leaf metabolites of V. unijuga. Results of physiological indicators indicated that Cupriavidus sp. WS2 had strong absorption and accumulation capacity of Cd, exogenous addition of strain WS2 remarkably decreased the Cd concentrations, and increased the plant heights, the biomass, the total protein concentrations, the chlorophyll contents and the photosynthetic rate in stems and leaves of V. unijuga under Cd stress. Cd treatment increased the abundance of Cd tolerant bacterial genera in rhizosphere microbiome, but these genera were down-regulated in the WS2/Cd group. Pseudotargeted metabolomic results showed that six common differential metabolites associated with antioxidant stress were increased after co-culture with WS2. In addition, WS2 activated the antioxidant system including glutathione (GSH) and catalase (CAT), reduced the contents of oxidative stress markers including malondialdehyde (MDA) and hydrogen peroxide (H2O2) in V. unijuga under Cd stress. Taken together, this study revealed that Cupriavidus sp.WS2 alleviated the toxicity of V. unijuga under Cd exposure by activating the antioxidant system, increasing the antioxidant metabolites, and reducing the oxidative stress markers.

Multiomics Reveals Mechanisms of Alternaria oxytropis Inhibiting Pathogenic Fungi in Oxytropis ochrocephala.

Endophytic fungi can benefit the host plant and increase the plant resistance. Now, there is no in-depth study of how Alternaria oxytropis (A. oxytropis) is enhancing the ability of inhibiting pathogenic fungi in Oxytropis ochrocephala (O. ochrocephala). In this study, the fungal community and metabolites associated with endophyte-infected (EI) and endophyte-free (EF) O. ochrocephala were compared by multiomics. The fungal community indicated that there was more A. oxytropis, less phylum Ascomycota, and less genera Leptosphaeria, Colletotrichum, and Comoclathris in the EI group. As metabolic biomarkers, the levels of swainsonine and apigenin-7-O-glucoside-4-O-rutinoside were significantly increased in the EI group. Through in vitro validation experiments, swainsonine and apigenin-7-O-glucoside-4-O-rutinoside can dramatically suppress the growth of pathogenic fungi Leptosphaeria sclerotioides and Colletotrichum americae-borealis by increasing the level of oxidative stress. This work suggested that O. ochrocephala containing A. oxytropis could increase the resistance to fungal diseases by markedly enhancing the content of metabolites inhibiting pathogenic fungi.

New-designed measurement device for radon and thoron activity concentration based on gas direct detection.

A new-designed measurement device for radon and thoron activity concentration is developed based on gas direct measurement to support their in-situ calibration. It consists of a 2000 mm2 Passivated Implanted Planar Silicon (PIPS) detector, a Multi-Channel Analyzer (MCA), a Micro Controller Unit (MCU), and a small electrostatic chamber with a volume of nearly 23 ml. The device records those alpha particles emitted from radon and thoron gas, and the detection efficiency and the crosstalk factor of 218Po/216Po are determined by Monte Carlo simulation. Measurement results have been compared with AlphaGUARD DF2000 in pure radon and thoron environments, respectively. Results show that the measurement results of the devices and the reference monitor agree well with each other, with an average relative deviation of 0.48% for radon gas from about 3300 Bq/m3 to 38 kBq/m3 and -3.25% for thoron gas from about 25 kBq/m3 to 70 kBq/m3. Uncertainty assessment has also been done, and a relative system uncertainty of radon is about 6.8%, while that of thoron is nearly 7.3%.

Biejiajian pill inhibits progression of hepatocellular carcinoma by downregulating PDGFRß signaling in cancer-associated fibroblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Biejiajian pill (BJJP) is a canonical formula that is clinically used to treat chronic liver disease, especially to decrease the incidence of hepatocellular carcinoma (HCC). However, the mechanisms underlying the prevention of HCC progression by BJJP remain unclear. AIM OF THE STUDY: This study aimed to determine whether BJJP inhibits HCC progression by downregulating platelet-derived growth factor receptor beta (PDGFRß) signaling in cancer-associated fibroblasts (CAFs) in a mouse model of diethylnitrosamine (DEN)/carbon tetrachloride (CCl4)-induced HCC. MATERIALS AND METHODS: C57BL/6 male mice were intraperitoneally injected with DEN 2 weeks after birth, followed by repeated injections of CCl4 weekly from 6 weeks of age onwards, to recapitulate features of HCC. At week 14, BJJP was orally administered to mice. The effects of BJJP on HCC progression were evaluated using histology, immunohistochemistry, and serum biochemical marker levels. Transcriptome analysis, molecular docking, quantitative real-time PCR, and Western blot were used to study the genes targeted by BJJP and the associated signaling pathway. The effects of BJJP on PDGFRß signaling in CAFs and the underlying mechanism were demonstrated. RESULTS: BJJP treatment significantly suppressed carcinogenesis and cancer progression, and it ameliorated liver inflammation in mice with HCC. A total of 176 genes, including PDGFRß, were significantly downregulated after BJJP treatment and five components of BJJP with high binding affinity to PDGFRß were identified. BJJP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK3ß) by suppressing PDGFRß expression in CAFs, and it also downregulated the expression of the downstream proteins hepatocyte growth factor (HGF) and vascular endothelial growth factor A (VEGF-A). Furthermore, BJJP-containing serum consistently reduced PDGFRß, HGF, and VEGF-A expression levels in HSC-derived CAFs in vitro. Importantly, PDGF-BB induced PDGFRß activation in CAFs and both BJJP and sunitinib (a kinase inhibitor) inhibited PDGF-BB/PDGFRß signaling. CONCLUSION: BJJP inhibits the progression of HCC through suppressing VEGF-A and HGF expression in CAFs by downregulating PDGFRß signaling.