Chronic stress influences the macrophage M1-M2 polarization balance through ß-adrenergic signaling in hepatoma mice.

Chronic stress negatively affects the immune system and promotes tumor progression. Tumor-associated macrophage (TAM) is an important component of the tumor immune microenvironment. However, the influence of chronic stress on M1-M2 polarization of TAM is unclear. We used flow cytometry to measure the M1-M2 polarization of TAM in chronic stress hepatocellular carcinoma (HCC) bearing mice. We also measured the level of norepinephrine and blocked ß-adrenergic signaling to explore the role of ß-adrenergic receptor in the effect of chronic stress on M1-M2 polarization of TAM. We found that chronic stress disrupts the M1-M2 polarization in tumor tissues, increased the level of CD11b+Ly6C+CCR2+ monocyte and interleukin-1beta in blood and promoted the growth of HCC. Furthermore, chronic stress upregulated the level of CCL2 in tumor tissues. Finally, we found chronic stress increased norepinephrine level in serum and propranolol, a blocker of ß-adrenergic signaling, inhibited HCC growth, recovered the M1-M2 polarization balance of TAM in tumor tissues, blocked the increase of CD11b+Ly6C+CCR2+ monocytes in blood, and blocked the increase of CCL2 in tumor tissues induced by chronic stress. Our study indicated that chronic stress disrupts the M1-M2 polarization balance of TAMs through ß-adrenergic signaling, thereby promoting the growth of HCC.

Visible-Light Self-Powered Photodetector with High Sensitivity Based on the Type-II Heterostructure of CdPSe3/MoS2.

Transition metal thiophosphates (MTPs) are a group of emerging van der Waals materials with widely tunable band gaps. In the MTP family, CdPSe3 is demonstrated to possess a wide energy band gap and high carrier mobility, making it a potential candidate in optoelectronic applications. Here, we reported photoelectric response behaviors of both CdPSe3- and CdPSe3/MoS2-based photodetectors (noted as CPS and CM, respectively); these showed prominent photoelectric performances, and the latter proved to be significantly superior to the former. These devices exhibited ultralow dark current at a magnitude order of 10-12 A and fine cycle and air stabilities. Compared with CPS, CM demonstrated the highest responsivity (91.12 mA/W) and detectivity (1.74 × 1011 Jones) at 5 V under 425 nm light illumination. Besides, CM showed self-powered photoelectric responses at zero bias, which was attributed to the improved separation efficiency of photogenerated carriers by the built-in electric field at the interface of the p-n junction. This work proves a prospect for the CM device in portable, self-powered optoelectronic device applications.

Spatial distribution and community composition of endophytic fungi within Mussaenda pubescens stems.

Endophytic fungi, pivotal in facilitating plant co-evolution, significantly enhance plant growth, stress resistance, and environmental adaptability. Despite their importance, the spatial distribution of stem endophytic fungi (SEF) within host plants remains poorly characterized. Here, we employed high-throughput sequencing to conduct a comparative analysis of SEF communities in Mussaenda pubescens on a regional scale. Our findings reveal that whole-SEF communities were overwhelmingly dominated by members of the phylum Ascomycota, accounting for 85.9 %, followed by Basidiomycota at 13.9 %, and that alpha diversity within the whole-SEF community of M. pubescens remains relatively consistent across sampling sites. However, significant variation was observed within conditionally abundant taxa (CAT), conditionally rare or abundant taxa (CRAT), and conditionally rare taxa (CRT). Climatic factors emerged as the primary influence on SEF community distribution, followed by spatial distance and stem chemical properties. Neutral community modeling results suggested that both stochastic and deterministic processes play a role in shaping whole-SEF communities, with deterministic processes having a stronger influence on CRT subcommunities. Furthermore, the CRT co-occurrence network exhibited a more complex structure, characterized by higher values of network betweenness and degree relative to CAT and CRAT subcommunities. These findings enhance our understanding of community assembly and ecological interactions between stem fungal endophytes, presenting opportunities for harnessing fungal resources for the benefit of humanity.

Community assembly of ectomycorrhizal fungal communities in pure and mixed Pinus massoniana forests.

Ectomycorrhizal (EcM) fungi play an important role in nutrient cycling and community ecological dynamics and are widely acknowledged as important components of forest ecosystems. However, little information is available regarding EcM fungal community structure or the possible relationship between EcM fungi, soil properties, and forestry activities in Pinus massoniana forests. In this study, we evaluated soil properties, extracellular enzyme activities, and fungal diversity and community composition in root and soil samples from pure Pinus massoniana natural forests, pure P. massoniana plantations, and P. massoniana and Liquidambar gracilipes mixed forests. The mixed forest showed the highest EcM fungal diversity in both root and bulk soil samples. Community composition and co-occurrence network structures differed significantly between forest types. Variation in the EcM fungal community was significantly correlated with the activities of ß-glucuronidase and ß-1,4-N-acetylglucosaminidase, whereas non-EcM fungal community characteristics were significantly correlated with ß-1,4-glucosidase and ß-glucuronidase activities. Furthermore, stochastic processes predominantly drove the assembly of both EcM and non-EcM fungal communities, while deterministic processes exerted greater influence on soil fungal communities in mixed forests compared to pure forests. Our findings may inform a deeper understanding of how the assembly processes and environmental roles of subterranean fungal communities differ between mixed and pure plantations and may provide insights for how to promote forest sustainability in subtropical areas.

Changes in temporal lobe activation during a sound stimulation task in patients with sensorineural tinnitus: a multi-channel near-infrared spectroscopy study.

BACKGROUND: The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. METHODS: In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. RESULTS: When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P < 0.05), and the healthy control group exhibited a high activation, according to the fNIRS measurement data. The blood oxygen concentration level in the patient group was dramatically enhanced after one month of acupuncture therapy under the identical stimulation task settings, and it was favorably connected with the levels of THI and TEQ scales. CONCLUSIONS: Using sensorineural tinnitus illness as an example, fNIRS technology has the potential to disclose future pathological study on subjective diseases throughout time. Other clinical disorders involving the temporal lobe and adjacent brain areas may also be examined, in addition to tinnitus-related brain alterations.

Impact of perinatal factors on meconium aspiration syndrome in full-term newborns and the construction of a column chart prediction model: An observational study.

To explore the influence of perinatal-related factors on meconium aspiration syndrome (MAS) in full-term neonates and construct a nomogram prediction model for risk stratification of neonatal MAS and adoption of preventive measures. A total of 424 newborns and their mothers who were regularly examined at our hospital between January 2020 and December 2023 who had meconium-contaminated amniotic fluid during delivery were retrospectively selected as participants. Neonates were divided into MAS and non-MAS groups based on whether MAS occurred within 3 days after birth. Data from the 2 groups were analyzed, and factors influencing MAS were screened using multivariate logistic regression analysis. The R3.4.3 software was used to construct a nomogram prediction model for neonatal MAS risk. Receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using a decision curve. Among the 424 neonates with meconium-stained amniotic fluid, 51 developed MAS within 3 days of birth (12.03%). Multivariate logistic regression analysis showed that a low amniotic fluid index before delivery (OR = 2.862, P = .019), advanced gestational age (OR = 0.526, P = .034), cesarean section (OR = 2.650, P = .013), severe amniotic fluid contamination (OR = 4.199, P = .002), low umbilical cord blood pH (OR = 2.938, P = .011), and low neonatal Apgar 1-min score (OR = 3.133, P = .006) were influencing factors of MAS in full-term neonates. Based on the above indicators, a nomogram prediction model for MAS risk of full-term newborns was constructed. The area under the ROC curve of the model was 0.931. The model was also tested for goodness-of-fit deviation (χ2 = 3.465, P = .903). Decision curve analysis found that the model was clinically effective in predicting the net benefit of MAS risk in neonates with meconium-stained amniotic fluid. The construction of a column chart prediction model for neonatal MAS risk based on prenatal amniotic fluid index, gestational age, delivery method, amniotic fluid contamination level, newborn umbilical blood pH value, and Apgar 1-min score has a certain application value.

Metabolomics perspectives into the co-exposure effect of polycyclic aromatic hydrocarbons and metals on renal function: A meet-in-the-middle approach.

Studies on the dose effects of kidney impairment and metabolomes in co-exposure to polycyclic aromatic hydrocarbons (PAHs) and metals are limited. We aimed to identify overall associations and metabolic perturbations in 130 participants (53 petrochemical workers and 77 controls) exposed to a PAHs-metals mixture in Southern China. The urinary 7 hydroxylated PAHs and 15 metal(loid)s were determined, and serum creatinine, beta-2 microglobulin, and estimated glomerular filtration rate were health outcomes. The liquid chromatography-mass spectrometry-based method was applied to serum metabolomics. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-response relationships, and pathway analysis, "meet-in-the-middle" approach, and mediation effect analyses were conducted to identify potential metabolites and biological mechanisms linking exposure with nephrotoxic effects. Our results indicated that renal function reduction was associated with a PAHs-metals mixture in a dose-dependent manner, and 1-hydroxynaphthalene and copper were the most predominant contributors among the two families of pollutants. Furthermore, the metabolic disruptions associated with the early onset of kidney impairment induced by the combination of PAHs and metals encompassed pathways such as phenylalanine-tyrosine-tryptophan biosynthesis, phenylalanine metabolism, and alpha-linolenic acid metabolism. In addition, the specifically identified metabolites demonstrated excellent potential as bridging biomarkers connecting the reduction in renal function with the mixture of PAHs and metals. These findings shed light on understanding the overall associations and metabolic mechanism of nephrotoxic effects of co-exposure to PAHs and metals.

A meta-analysis of the association between post-traumatic stress disorder and cancer risk.

Background: Several studies have investigated the link between post-traumatic stress disorder (PTSD) and cancer risk but reported mixed results. The objective of our study was to investigate the association between PTSD and cancer risk. Methods: Studies published in English about the relationship between PTSD and cancer incidence were systematically searched. We performed a meta-analysis to estimate the relative risks (RR) and 95% confidence intervals (CI) for cancer incidence. Result: A total of 3,129 articles were screened. Finally, 8 articles and 11 studies were included in the meta-analysis. We found that PTSD was not associated with cancer risk compared with controls. For site-specific cancer, our results showed that women with PTSD were associated with higher risk of ovarian cancer than controls. However, PTSD was not associated with the risk of gastrointestinal cancer, breast cancer and lung cancer. Conclusion: These analyzes based on studies published in English suggest that PTSD is associated with ovarian cancer risk, although the evidence base is very limited. Future studies are needed to investigate the mechanisms that PTSD diagnosis influenced cancer incidence depending on types of cancer.

Gastric ectopic pancreas adenocarcinoma: A case report and literature review.

The incidence of malignant transformation in ectopic pancreas (EP), including adenocarcinoma, is extremely rare. Herein, we presented a single case with invasive adenocarcinoma caused by the EP in the stomach. The patient consulted our hospital due to abdominal discomfort with acid regurgitation. Computed tomography scan showed a pyloric obstruction and thickening of the gastric wall in the gastric antrum; a digestive endoscopic examination showed mucosal congestion, swelling in the anterior pyloric area, and pyloric canal stenosis. Next, the patient underwent gastrointestinal surgery, and the distal gastrectomy specimens revealed a deviation of 10 cm towards the lesser curvature and an extension of 22 cm towards the greater curvature. A 5.5 x 5.4 cm round-like mass was found during surgery. Pathological examination suggested invasive submucosal adenocarcinoma located under the gastric antrum mucosa. Our report provides additional clinical experience for diagnosing EP with canceration in the stomach.

Identification of highly potent 2,4-diarylaminopyrimidine analogs of a typical piperidinyl-4-ol moiety as promising antitumor ALK inhibitors.

In light of the cocrystal structure of ceritinib with anaplastic lymphoma kinase (ALK)WT protein, a series of novel 2,4-diarylaminopyrimidine analogs (L1-L25) bearing a typical piperidinyl-4-ol moiety were designed and synthesized with improved biological and physicochemical properties. Satisfyingly, most compounds demonstrated moderate to excellent antitumor effects with IC50 values below 5 µM on ALK-positive Karpas299 and H2228 cells. In particular, L6 bearing the 1-(6-methoxy-pyridin-2-yl)-4-(morpholinomethyl)piperidinyl-4-ol moiety was detected as the optimal compound against ALK-dependent cell lines of Karpas299 (0.017 µM) and H2228 cells (0.052 µM), in company with encouraging ALK enzyme inhibition (ALKWT , IC50 = 1.8 nM). In addition, L6 was also capable of inhibiting ALK-resistant mutations, including ALKL1196M (3.9 nM) and ALKG1202R (5.2 nM). Remarkably, L6 typically repressed colony formation and migration of H2228 cells in a dose-dependent manner. Meanwhile, acridine orange-ethidium bromide staining analysis indicated that the proapoptotic effect of L6 was better than that of ceritinib at the same concentration (50 nM). Ultimately, the binding patterns of L6 to ALKWT and ALKG1202R were ideally established, which further confirmed the structural basis in accordance with the structure-activity relationship analysis.

Combined ARHGEF6 and Tumor Mutational Burden may serve as a potential biomarker for immunotherapy of lung adenocarcinoma.

ARHGEF6, a member of the Dbl-related guanylate exchanger (GEF) family, is highly expressed in gastric cancer and glioma. However, scientists still do not know whether it plays a pivotal role in the pathogenesis of lung adenocarcinoma（LUAD）. The prognostic significance of ARHGEF6 expression was assessed by TCGA data. This paper focuses on the level of immune infiltration associated with ARHGEF6 and explored the relationship of this gene with the tumor mutational burden (TMB), immune checkpoints, and drug sensitivity. The results showed that the high expression of ARHGEF6 was associated with a good prognosis in LUAD patients, and positively correlated with a variety of immune cells and drugs. Meanwhile, ARHGEF6 was found to be negatively correlated with TMB. In conclusion, the results of this study suggest that ARHGEF6 is a protective gene in LUAD patients. A combination of ARHGEF6 and TMB could be used as a potential biomarker in the screening of immunotherapy regimens, which are provided to patients with LUAD.

Association between immune cells in peripheral blood and psychiatric symptoms.

Background: There are bidirectional associations between immunological dysfunction and psychiatric symptoms. However, the associations between the levels of immune cells in the peripheral blood and psychiatric symptoms remain unclear. The present study aimed to evaluate levels of immune cells in peripheral blood in people with positive psychiatric symptoms. Methods: This retrospective study analyzed data from routine blood tests and psychopathology and sleep quality assessments. Data were compared between a group of 45 patients with de novo psychological symptoms and 225 matched controls. Results: Patients with psychiatric symptoms had higher white blood cell and neutrophil counts compared with controls. However, in a subgroup analysis, neutrophil counts were significantly higher than in controls only in patients with multiple psychiatric symptoms. Furthermore, monocyte counts were significantly higher in patients with multiple psychiatric symptoms than in controls. Further, sleep quality was lower in patients with psychiatric symptoms than in controls. Conclusion: White blood cell and neutrophil counts in the peripheral blood of patients with psychiatric symptoms were significantly higher and sleep quality was significantly lower than in controls. Participants with multiple psychiatric symptoms showed more significant differences in peripheral blood immune cell counts than other subgroups. These results provided evidence for the relationship between psychiatric symptoms, immunity, and sleep.

Modulating Lipid Membrane Morphology by Dynamic DNA Origami Networks.

Membrane morphology and its dynamic adaptation regulate many cellular functions, which are often mediated by membrane proteins. Advances in DNA nanotechnology have enabled the realization of various protein-inspired structures and functions with precise control at the nanometer level, suggesting a viable tool to artificially engineer membrane morphology. In this work, we demonstrate a DNA origami cross (DOC) structure that can be anchored onto giant unilamellar vesicles (GUVs) and subsequently polymerized into micrometer-scale reconfigurable one-dimensional (1D) chains or two-dimensional (2D) lattices. Such DNA origami-based networks can be switched between left-handed (LH) and right-handed (RH) conformations by DNA fuels and exhibit potent efficacy in remodeling the membrane curvatures of GUVs. This work sheds light on designing hierarchically assembled dynamic DNA systems for the programmable modulation of synthetic cells for useful applications.

Impact of Beta Blockers on Breast Cancer Incidence and Prognosis.

Several studies have investigated the link between beta blockers (BB) and breast cancer outcomes but have reported mixed results. Our aim was to investigate the relationship between BB and breast cancer outcomes. Literatures investigating the relationship between BB and breast cancer outcomes were searched through PubMed and Embase. A total 43 articles were included by meta-analysis. We found BB increased breast cancer risk (n = 22, RR: 1.169, 95% CI: 1.063-1.285). We also found BB were associated with a lower overall survival (OS, n = 19, RR: 1.125, 95% CI: 1.078-1.173) and a higher recurrence risk (n = 8, RR: 1.130, 95% CI: 1.040-1.227) for breast cancer. Interestingly, subgroup analyses found only selective BB increased breast cancer risk (n = 5, RR: 1.766, 95% CI: 1.148-2.718) and recurrence risk (n = 2, RR: 1.168 -, 95% CI: 1.026-1.328) while only nonselective BB were associated with a lower OS (n = 4, RR: 1.135, 95% CI: 1.073-1.202) for breast cancer. Moreover, we found BB were associated with a significantly lower OS (n = 3, RR: 2.751, 95% CI: 1.213-6.238) and higher recurrence (n = 2, RR: 1.284, 95% CI: 1.102-1.497) only in luminal breast cancer while with a higher PFS (n = 2, RR: 0.585, 95% CI: 0.343-0.997) in Her2+ breast cancer. No significant differences in terms of CSM (n = 19, RR: 1.009, 95% CI: 0.947-1.077), PFS (n = 4, RR: 0.932, 95% CI: 0.616-1.305), and DFS (n = 2, RR: 0.776, 95% CI: 0.512-1.176) were observed. Our results provide evidence of the relationship between BB and breast cancer incidence and prognosis.

Double filtration plasmapheresis for children with different types of critical kidney diseases: a single-center retrospective cohort study.

Background: Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Methods: Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Results: Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. Conclusions: The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer.

Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity. Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism. Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA-transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan-Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models. Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients. Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

Nasal mucosal care before and after nasal endoscopic surgery based on computational information system resource sharing technology.

This study presents an in-depth analysis on a machine-designed computational web-based information system, which was used to conduct nasal mucosal care before and after nasal endoscopic surgery for chronic sinusitis. The system was developed and implemented using the mainstream B/S structure model with a Java development framework and MySQL database. Sinus irrigation solution has been shown to be effective for postoperative flushing after nasal endoscopy, by eliminating mucosal edema and promoting mucosal epithelialization at the operative cavity, and it is currently a desirable method that deserves promotion. By comparing the time required for surgical cavity cleaning, the rinsing solution was shown to be key of the physical flushing effect in the initial period after nasal endoscopy. It could remove blood cemented and surgical cavity surface cemented skin and secretions. In addition, the sinus irrigation solution can accelerate the mucosal epithelialization of the operative cavity more effectively than compounded saline. It could effectively eliminate mucosal edema, restore its protective and defensive functions, and help local blood circulation, secretion absorption, mucosal growth, mucosal regeneration and repair, and mucus cilia removal.

Replacing the tropolonic methoxyl group of colchicine with methylamino increases tubulin binding affinity with improved therapeutic index and overcomes paclitaxel cross-resistance.

AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.

The Diagnosis of Congestive Heart Failure Based on Generalized Multiscale Entropy-Wavelet Leaders.

Congestive heart failure (CHF) is a chronic heart condition associated with debilitating symptoms that can lead to mortality. The electrocardiogram (ECG) is a noninvasive and simple diagnostic method that can show detectable changes in CHF. However, manual diagnosis of ECG signals is often erroneous due to the small amplitude and duration of the ECG signals. This paper presents a CHF diagnosis method based on generalized multiscale entropy (MSE)-wavelet leaders (WL) and extreme learning machine (ELM). Firstly, ECG signals from normal sinus rhythm (NSR) and congestive heart failure (CHF) patients are pre-processed. Then, parameters such as segmentation time and scale factor are chosen, and the multifractal spectrum features and number of ELM hidden layer nodes are determined. Two different data sets (A, B) were used for training and testing. In both sets, the balanced data set (B) had the highest accuracy of 99.72%, precision, sensitivity, specificity, and F1 score of 99.46%, 100%, 99.44%, and 99.73%, respectively. The unbalanced data set (A) attained an accuracy of 99.56%, precision of 99.44%, sensitivity of 99.81%, specificity of 99.17%, and F1 score of 99.62%. Finally, increasing the number of ECG segments and different algorithms validated the probability of detection of the unbalanced data set. The results indicate that our proposed method requires a lower number of ECG segments and does not require the detection of R waves. Moreover, the method can improve the probability of detection of unbalanced data sets and provide diagnostic assistance to cardiologists by providing a more objective and faster interpretation of ECG signals.

Mapping network connectivity between internet addiction and residual depressive symptoms in patients with depression.

Background and aims: Depression often triggers addictive behaviors such as Internet addiction. In this network analysis study, we assessed the association between Internet addiction and residual depressive symptoms in patients suffering from clinically stable recurrent depressive disorder (depression hereafter). Materials and methods: In total, 1,267 depressed patients were included. Internet addiction and residual depressive symptoms were measured using the Internet Addiction Test (IAT) and the two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices. Network stability was examined using the case-dropping procedure. Results: The prevalence of IA within this sample was 27.2% (95% CI: 24.7-29.6%) based on the IAT cutoff of 50. IAT15 ("Preoccupation with the Internet"), IAT13 ("Snap or act annoyed if bothered without being online") and IAT2 ("Neglect chores to spend more time online") were the most central nodes in the network model. Additionally, bridge symptoms included the node PHQ1 ("Anhedonia"), followed by PHQ2 ("Sad mood") and IAT3 ("Prefer the excitement online to the time with others"). There was no gender difference in the network structure. Conclusion: Both key central and bridge symptoms found in the network analysis could be potentially targeted in prevention and treatment for depressed patients with comorbid Internet addiction and residual depressive symptoms.