Positive roles of the Ca2+ sensors GbCML45 and GbCML50 in improving cotton Verticillium wilt resistance.

As a universal second messenger, cytosolic calcium (Ca2+) functions in multifaceted intracellular processes, including growth, development and responses to biotic/abiotic stresses in plant. The plant-specific Ca2+ sensors, calmodulin and calmodulin-like (CML) proteins, function as members of the second-messenger system to transfer Ca2+ signal into downstream responses. However, the functions of CMLs in the responses of cotton (Gossypium spp.) after Verticillium dahliae infection, which causes the serious vascular disease Verticillium wilt, remain elusive. Here, we discovered that the expression level of GbCML45 was promoted after V. dahliae infection in roots of cotton, suggesting its potential role in Verticillium wilt resistance. We found that knockdown of GbCML45 in cotton plants decreased resistance while overexpression of GbCML45 in Arabidopsis thaliana plants enhanced resistance to V. dahliae infection. Furthermore, there was physiological interaction between GbCML45 and its close homologue GbCML50 by using yeast two-hybrid and bimolecular fluorescence assays, and both proteins enhanced cotton resistance to V. dahliae infection in a Ca2+-dependent way in a knockdown study. Detailed investigations indicated that several defence-related pathways, including salicylic acid, ethylene, reactive oxygen species and nitric oxide signalling pathways, as well as accumulations of lignin and callose, are responsible for GbCML45- and GbCML50-modulated V. dahliae resistance in cotton. These results collectively indicated that GbCML45 and GbCML50 act as positive regulators to improve cotton Verticillium wilt resistance, providing potential targets for exploitation of improved Verticillium wilt-tolerant cotton cultivars by genetic engineering and molecular breeding.

Direct α-Arylation of Benzo[b]furans Catalyzed by a Pd3 Cluster.

As an interim paradigm for the catalysts between those based on more conventional mononuclear molecular Pd complexes and Pdn nanoparticles widely used in organic synthesis, polynuclear palladium clusters have attracted great attention for their unique reactivity and electronic properties. However, the development of Pd cluster catalysts for organic transformations and mechanistic investigations is still largely unexploited. Herein, we disclose the use of trinuclear palladium (Pd3Cl) species as an active catalyst for the direct C-H α-arylation of benzo[b]furans with aryl iodides to afford 2-arylbenzofurans in good yields under mild conditions. With this method, broad substrate adaptability was observed, and several drug intermediates were synthesized in high yields. Mechanistic studies indicated that the Pd3 core most likely remained intact throughout the reaction course.

Using Mathematical and Statistical Analysis to Investigate the Correlation between Exacerbation of Chronic Obstructive Pulmonary Disease and Risk of Subclinical Atherosclerosis.

Purpose: As the number of patients with chronic obstructive pulmonary disease continues to increase, it is increasingly important to understand the impact of cardiovascular risk on the progression of chronic obstructive pulmonary disease, which can provide guidance for clinical medication and recommendations for patient care and rehabilitation. The purpose of this study was to investigate the relationship between cardiovascular risk and the progression of chronic obstructive pulmonary disease (COPD). Methods: Selected COPD patients admitted to hospital from June 2018 to July 2020 were included in the study for prospective analysis, and patients who showed more than two instances of moderate deterioration or severe deterioration within one year before the consultation were defined as COPD patients, and all participants underwent relevant tests and assessments. Results: Multivariate correction analysis showed that a worsening phenotype improved the risk of carotid artery intima-media thickness exceeding 75% by nearly three times, and it had no relation with the degree of COPD severity and global cardiovascular risk; in addition, the relationship between a worsening phenotype and high carotid intima-media thickness (c-IMT) was more pronounced in patients under 65 years of age. Conclusions: The existence of subclinical atherosclerosis is individually related to the worsening phenotype, and the difference is more obvious in young patients. Therefore, the control of vascular risk factors in these patients should be strengthened.

Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones.

Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were upregulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but downregulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA- and ABA-signaling pathways and by inducing ROS accumulation.

Is Phenotypic Evolution Affected by Spiders' Construction Behaviors?

What happens when organisms actively modify their environment? Clarifying the role of construction behavior on a macroevolutionary scale is crucial to interpreting phenotypic evolution. Spiders, an extremely successful group of animals exhibiting a wide variety of functional, morphological, and behavioral diversity, are ideal candidates to test whether animal behaviors are related to their phenotypic evolution. Herein, we reconstructed the phylogenomic relationships of 303 spiders covering 105 families with 99 newly developed molecular markers that universally apply across Araneae, and explicitly tested the potential link between construction behavior and somatic evolution based on extensive morphological data from 3,342 extant species and 682 fossil species. Our dated molecular phylogeny provides the backbone for analyses, revealing the behavioral and ecological processes behind these spiders' morphological adaptations. Evolutionary model analyses showed the artifacts constructed by spiders, especially the suspending webs, expand the spider's ability to inhabit different habitats. These artifacts have more substantial impacts on their somatic traits than habitats and promote different trajectories of morphological evolution. Specifically, for spiders, silk-lined burrowing produced larger bodies, relatively shorter legs, and longer patellae, while web-building produced smaller bodies, relatively longer legs, and shorter patellae, and hunting promoted an intermediate morphological size. Molecular convergence analysis showed that genes related to morphogenesis or response to stimulus and stress are enriched in spiders with construction behavior. Our study demonstrated that the construction behavior of an animal plays a crucial role in determining the direction and intensity of the selection pressure imposed on it and provides strong evidence that construction behaviors are associated with phenotypic evolution on macroevolutionary timescales. [Araneae; body size; habitat change; molecular marker; leg length; phylogenomics.].

Dust dominates the summer melting of glacier ablation zones on the northeastern Tibetan Plateau.

Dust and black carbon (BC) can darken snow and ice surface and play pivotal roles in glacier mass loss. Thus, a quantitative assessment of their contributions to glacier summer melting is critical. During the summer of 2018, surface snow and ice were sampled, and the albedo and mass balance were continuously measured in the ablation zone of Laohugou Glacier No. 12 in the western Qilian Mountains. The physical properties of dust and BC were measured in the laboratory, and their impacts on glacier surface albedo reduction and melting were simulated. The results indicate that the ice surface in the ablation zone was enriched with substantial amounts of particles, and the average particle concentrations of these samples were hundreds of times higher than those of fresh snow. The BC mass absorption cross-sections (MACs) ranged from 3.1 m2 g-1 at 550 nm for dirty ice to 4.6 m2 g-1 for fresh snow, largely owing to meltwater percolation and particle collapse. The spectral variations in dust MACs were significantly different in the visible light bands and near-infrared bands from those in the other areas. Moreover, the two-layer surface energy and mass balance model with the new albedo parameterization formula was validated and agreed well with the experimental measurements of spectral albedo, broadband albedo, and mass balance. BC and dust combined resulted in 26.7 % and 54.4 % of the total mass loss on the cleaner and dirtier (particle enriched) surfaces in the ablation zone, respectively, compared to particle-free surfaces, and although both impurities played vital roles, dust was the more prominent factor in accelerating glacier melting on the northeastern Tibetan Plateau. This study emphasizes the importance of dust in cryosphere changes where Tibetan glaciers are strongly affected by Asian dust deposition.

Clinical Study on the Efficacy of Bevacizumab in Combination with Pembrolizumab on Cellular Immune Function in the Treatment of Driver Gene-Negative Stage IV Lung Adenocarcinoma.

Purpose: To explore the efficacy of bevacizumab in combination with PD-1 immune drug pembrolizumab on cellular immune function in the treatment of driver gene-negative stage IV lung adenocarcinoma and its short-term survival effect. Methods: From February 2020 to December 2021, 85 patients with driver gene-negative stage IV lung adenocarcinoma were admitted to our hospital and treated with first-line therapy, and their clinical records were reviewed retrospectively. According to the treatments, the patients were separated into two groups the combination group (n = 45) and the control group (n = 40). The treatment regimen of the control group was an AP chemotherapy regimen (pemetrexed combined with cisplatin) + PD-1 immune drug pembrolizumab. The treatment regimen of the combination group was AP chemotherapy regimen + PD-1 immune drug pembrolizumab combined with bevacizumab. We evaluated the pre- and post-treatment cellular immunological function of the two patient groups and discussed the difference between them. Results: There was a substantial difference in the overall effective rate and the disease control rate between the two groups, with the former being 27.50% compared to 48.89% and the latter being 72.50% compared to 93.33% among these 85 patients studied. The KPS for the combination group improved and stayed at 91.11% after treatment, which is considerably better than the KPS for the control group, which was 42.50% (χ 2 = 23.09, P < 0.05). There was no significant difference (P > 0.05) in the numbers of CD3+, CD4+, CD19+, CD8+, or CD4+/CD8+ cells pretreatment between the two groups, but after treatment, the combination group had significantly higher numbers of all these cells. Neither the CD8+ nor the CD19+ level was significantly different between the control and combination groups (P > 0.05). Furthermore, the incidence of common clinical side effects was similar between the two groups (P > 0.05). Proteinuria, tiredness, increased alanine aminotransferase, hypertension, immunological pneumonia, muscle pain, arthralgia, hypothyroidism, etc. were the most common side effects reported among both groups throughout therapy. A grade IV side effect is rare. After follow-up until March 2022, the median PFS for the control group was 9.00 ± 1.65 months (95% CI, 5.76-12.24) and the mean PFS was 11.48 ± 0.91 months (95% CI, 9.69-13.26). Comparison of the median PFS of the combination group (13.00 ± 1.10) months (95% CI: 10.84-15.16) with the average PFS of the group (15.52 ± 0.88) months (95% CI = 13.79-17.25) reveals a statistically significant difference (P < 0.05). Conclusion: Combining bevacizumab with the PD-1 immune medication pembrolizumab to treat patients with stage IV lung adenocarcinoma improves the quality of life, short-term therapeutic effectiveness, immune function, and PFS.

A Tibetan ice core covering the past 1,300 years radiometrically dated with 39Ar.

Ice cores from alpine glaciers are unique archives of past global and regional climate conditions. However, recovering climate records from these ice cores is often hindered by the lack of a reliable chronology, especially in the age range of 100 to 500 anni (a) for which radiometric dating has not been available so far. We report on radiometric 39Ar dating of an ice core from the Tibetan Plateau and the construction of a chronology covering the past 1,300 a using the obtained 39Ar ages. This is made possible by advances in the analysis of 39Ar using the laser-based detection method atom trap trace analysis, resulting in a twofold increase in the upper age limit of 39Ar dating. By measuring the anthropogenic 85Kr along with 39Ar we quantify and correct modern air contamination, thus removing a major systematic uncertainty of 39Ar dating. Moreover, the 85Kr data for the top part of the ice core provide information on firn processes, including the age difference between the ice and its enclosed gas. This first application of 39Ar and 85Kr to an ice core facilitates further ice cores from nonpolar glaciers to be used for recovering climate records of the Common Era, a period including pronounced anomalies such as the Little Ice Age and the Medieval Warm Period.

In lung adenocarcinoma, low expression of the cell surface extracellular nucleotidase CD39 is related to immune infiltration and a poor prognosis.

Background: Extracellular nucleotidase on the cell surface CD39 plays a crucial role in the tumor microenvironment in the immunosuppressive adenosine pathway. However, the association between CD39 and lung adenocarcinoma has rarely been recorded. This study aimed to explore the involvement of CD39 in the biological processes of lung cancer. Methods: First, a prediction model was established by analyzing the expression of CD39 in lung adenocarcinoma and its relationships with clinical evidence of lung adenocarcinoma using The Cancer Genome Atlas (TCGA) and Tumor IMmune Estimation Resource (TIMER) databases. In the TCGA and TIMER databases, the relationship between CD39 and immune cells and the relationship with immune-related expressed genes were studied. Subsequently, using gene set enrichment analysis (GSEA), the potential mechanism of action was investigated. Results: Lung adenocarcinoma patients with elevated CD39 expression had improved overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). CD39 expression was reduced in lung adenocarcinoma tumor tissue in the TCGA and TIMER databases. The nomogram's C-index was 0.688 (0.665-0.712), indicating some consistency in the prediction model. According to the TIMER and TCGA databases, CD39 expression was strongly connected with several immune cells invading and with immune checkpoint-related markers such as PDCD1, CD274, CTLA-4, and several functional T cells. GSEA revealed that CD39 influences the extracellular matrix, immunological microenvironment, programmed death 1 (PD-1) expression, glucose metabolism, PTEN stability, inflammatory response, and angiogenesis in lung cancer. Conclusions: The current study's findings demonstrated that CD39 can be employed as a possible predictive biomarker for lung adenocarcinoma and may enhance the patients' poor prognosis by preventing the immunological escape of tumor cells from the lung adenocarcinoma tumor microenvironment.

Downregulation of LINC00115 inhibits the proliferation and invasion of lung cancer cells in vitro and in vitro.

BACKGROUND: Lung cancer is a common malignant tumor in clinical practice. Its morbidity and mortality rank first among malignant tumors. However, the pathogenesis of lung cancer has not been fully clarified. This study found that LINC00115 is highly expressed in lung cancer tissues, but the role and molecular mechanisms of LINC00115 in the occurrence and progression of lung cancer are still unclear. METHODS: Fluorescence quantitative PCR was used to detect the expression of LINC00115 in lung cancer tissues and para-carcinoma tissues. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect the effects of LINC00115 knockdown on the proliferation, clone formation, invasion, and migration of lung cancer cells. Western blot was used to detect the effects of LINC00115 knockdown on the expression of epithelial-mesenchymal transition (EMT)-related molecules. Finally, a xenograft model in nude mice was used to detect the effect of LINC00115 knockdown on the proliferation of lung cancer cells in vivo. RESULTS: Compared with para-carcinoma tissue, LINC00115 was highly expressed in lung cancer tissue. Cell function experiments showed that knockdown of LINC00115 could significantly inhibit the proliferation, invasion, and migration of lung cancer cells. Western blot results showed that knockdown of LINC00115 could significantly inhibit the expression of the EMT-related proteins N-cadherin, vimentin, and fibronectin, and promoted the expression of E-cadherin. In vivo experiments in nude mice showed that knockdown of LINC00115 could significantly inhibit the proliferation of lung cancer tissues in vivo. CONCLUSIONS: LINC00115 is highly expressed in lung cancer tissues, and knockdown of LINC00115 can significantly inhibit the proliferation and invasion of lung cancer, which provides a theoretical basis for the design of targeted molecules for the subsequent treatment of lung cancer.

Anticancer Effect of Troxerutin in Human Non-Small-Cell Lung Cancer Cell A549 and Inhibition of Tumor Formation in BALB/c Nude Mice.

This study is intended to explore the anticancer, antiproliferative, and chemopreventive action of troxerutin (TX) in human non-small-cell lung cancer cell (A549) using BALB/c nude mice. 2 × 106 A549 cells were subcutaneously injected into mice, along with 10 µM and 20 µM/kg body weight of TX orally for 19 days. On the last day, tumor weight and volume were assessed. Stress marker enzymes such as Aryl hydrocarbon hydroxylase (AHH), lactate dehydrogenase (LDH), 5'Nucleotidase (5'ND), and γ-glutamyltranspeptidase (γ-GT) were estimated in the lung tissues. Cytotoxicity of TX was assessed using MTT assay. Expression of carcinoembryonic antigen (CEA) and inflammatory cytokines were also analyzed. Histopathological examination of tissue sections and immunohistochemical examination of proliferating cell nuclear antigen (PCNA) were also performed. mRNA expression of p53, p21, cyclin D1, P13k, Akt, and mTOR were analyzed using RT-PCR. TX administered orally in a dose-dependent manner markedly reverted the level of stress marker enzymes to a significant extent. TX also exhibited significant protection against lung cancer cells, as evidenced by cytotoxicity assay and histopathological studies. It was also found to reduce the expression of PCNA, cyclin D1, P13k, Akt, and mTOR, but increase the expression of p53 and p21. TX has also been shown to reduce cancer cell inflammation, as was evidenced by reduced expression of inflammatory cytokines. Thus TX could be used as an effective chemopreventive and anticancer agent in treating cancer.

DUSP1 regulates hippocampal damage in epilepsy rats via ERK1/2 pathway.

OBJECTIVE: To investigate the effects of DUSP1 on the hippocampal injury of young rats with epilepsy (EP) through mediating ERK1/2 signaling pathway. METHODS: Young SD rats were selected and divided into Control, EP, EP + LV-GFP, EP + LV-DUSP1, EP + LV-siDUSP1, and EP + LV-siDUSP1 + U0126 groups. Morris Water Maze Test was used to detect the spatial learning and memory. Nissl staining and TUNEL staining were conducted and the inflammatory factors and oxidative stress-related indicators were also measured. Western blotting was utilized to detect the expression of DUSP1 and ERK1/2 pathway. EP cell model was constructed in vitro to verify the in vivo results. RESULTS: Compared with Control group, young rats in EP group had decreased spatial learning and memory abilities and increased apoptotic rate and decreased number of Nissl positive cells. Besides, the up-regulated levels in inflammatory factors (IL-1ß, IL-6), MDA content, and p-ERK1/2/ERK1/2 protein expression, as well as the down-regulated levels in DUSP1 protein expression and SOD content were also observed in EP rats. The EP rats treated with LV-DUSP1 showed obvious improvements regarding the above indicators, while those treated with LV-siDUSP1 had aggravated injury. But the effect of LV-siDUSP1 can be reversed by the treatment with ERK1/2 pathway inhibitor U0126. Further in vitro investigation verified the in vivo results. CONCLUSION: DUSP1 may ameliorate the oxidative stress and inflammatory injury, as well as improve spatial learning and memory abilities via inhibiting ERK1/2 pathway, eventually playing protective roles in hippocampal injury of young rats with EP.

B7-H3 on breast cancer cell MCF7 inhibits IFN-γ release from tumour-infiltrating T cells.

B7-H3 is a type I membrane protein that has contradictory co-stimulatory and co-inhibitory effects in adaptive and anti-tumour immunity. B7-H3 is up-regulated in many malignant tumours, including breast cancer. Therefore, we hypothesise that B7-H3, which has an immunosuppressive role, suppresses anti-tumour immunity. The aim of this study was to clarify the role of B7-H3 in the tumor microenvironment in breast cancer, explore the possibility of B7-H3 as a target for clinical immunotherapy, and provide reference for clinical work. We knocked down B7-H3 with siRNA in MCF7 breast cancer cells, which we termed MCF7-B7-H3-KD cells, and the expression of B7-H3 was assessed by flow cytometry. GAPDH (glyceraldehyde-3-phosphate dehydrogenase) knockdown was used as a control (MCF7-Gapdh). MCF7-B7-H3-KD and MCF7-Gapdh cells were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD3+ T cells from healthy donors to assess the effect of B7-H3 loss. PBMCs cultured with MCF7-Gapdh cells showed decreased activation, proliferation, and function of CD8+ T cells, but there was no effect on the proliferation of CD4+ T cells. However, when MCF7-B7-H3-KD cells were co-cultured with PBMCs, the proliferation ability of CD4+ T cells and CD8+ T cells was significantly higher than that observed in MCF7-Gapdh cell co-culture. Additionally, co-culture with MCF7-Gapdh cells decreased the expression of IFN-γ (Interferon-γ). However, after co-culture with MCF7-B7-H3-KD cells, there was an increase in IFN-γ. We further found that this inhibitory effect on IFN-γ was because of decreased mTOR (the mammalian target of rapamycin) phosphorylation in T cells. Treatment of T cells co-cultured with MCF7-B7-H3-KD cells with an mTOR inhibitor blocked the secretion of IFN-γ. B7-H3 on tumour cells inhibits the proliferation of CD4+ and CD8+ T cells and inhibits the release of IFN-γ by decreasing mTOR signalling. A better understanding of these complex immune regulatory mechanisms should facilitate the generation of more powerful and selective tools to manipulate cancer therapy.

Black carbon and dust in the Third Pole glaciers: Revaluated concentrations, mass absorption cross-sections and contributions to glacier ablation.

In snow and ice, light-absorbing particles (LAPs), such as black carbon (BC) and dust, accelerate the melting of Third Pole glaciers (TPGs). In this study, we revaluated LAP concentrations in the snow pits of TPGs (SP-TPGs), measured LAP mass absorption cross-sections (MACs), and simulated their effects on glacier darkening and melting based on the Spectral Albedo Model for Dirty Snow and a surface energy and mass balance model. The results indicated that because of their short distances to emission sources, the average BC concentrations measured in snow pits in the periphery of Third Pole were much higher than those measured in the inland Tibetan Plateau, and the average dust concentrations generally decreased from north to south. The average MACs of BC in the SP-TPGs varied from 3.1 to 7.7 m2 g-1 at 550 nm, most of the average spectral values were comparable in the visible and near-infrared bands to those calculated by Mie theory, except those in Urumqi Glacier No. 1 (UR), Syek Zapadniy Glacier (SZ), and Laohugou Glacier No.12 (LH), while the average spectral MACs of dust in the SP-TPGs were considerably smaller in magnitude than most of the variations measured in other regions. Compared with the pure snow surfaces, BC and dust played comparable roles in reducing albedo in UR, SZ, LH, and Renlongba Glacier, whereas BC was the most prominent absorber in the other glaciers. The combined effect of BC and dust accelerated melting by 30.4-345.9 mm w.e. (19.7-45.3% of the total mass balance) through surface albedo darkening (0.06-0.17) and increased radiation absorption (25.8-65.7 W m-2) within one month of the ablation season. This study provides a new data set of LAP concentrations and MACs and helps to clarify the roles of these factors in the cryospheric environment of the Third Pole.

Altered miR-93-5p/miR-18a expression in serum for diagnosing non-small cell lung cancer.

OBJECTIVE: This research aimed at probing into miR-93-5p and miR-18a's diagnostic and prognostic values in non-small cell lung cancer (NSCLC) patients. METHODS: A total of 107 patients diagnosed with NSCLC in the Department of Oncology and Thoracic Surgery of our hospital from January 2015 to June 2016 were regarded as the research group (RG), and 42 healthy people were considered as the control group (CG). Serum samples were collected and miR-93-5p, miR-18a expression was detected via qPCR. The relationship between miR-93-5p, miR-18a and clinicopathological characteristics of NSCLC patients was assessed, and the diagnostic value of the two miRNAs was analyzed by ROC curve. RESULTS: miR-93-5p and miR-18a were up-regulated in NSCLC. The higher the degree of tumor differentiation, the higher the TNM stage and the expression of the two miRNAs were. The high expression was tied to tumor differentiation degree, TNM stage, lymph node metastasis and lymph-vascular space invasion (LVSI). The survival rate of miR-93-5p and miR-18a high expression patients was worse than that of those with low expression. The AUC value of both of the mRNAs in NSCLC diagnosis was high (0.8905). CONCLUSION: The expression of miR-93-5p and miR-18a is associated with NSCLC severity and prognosis, and both can be used as potential markers for diagnosis.

Anti-HBV Activities of Polysaccharides from Thais clavigera (Küster) by In Vitro and In Vivo Study.

Hepatitis B virus (HBV) infection remains a major global health problem. It is therefore imperative to develop drugs for anti-hepatitis B with high-efficiency and low toxicity. Attracted by the observations and evidence that the symptoms of some patients from the Southern Fujian, China, suffering from hepatitis B were alleviated after daily eating an edible marine mollusk, Thais clavigera (Küster 1860) (TCK). Water-soluble polysaccharide from TCK (TCKP1) was isolated and characterized. The anti-HBV activity of TCKP1 and its regulatory pathway were investigated on both HepG2.2.15 cell line and HBV transgenic mice. The data obtained from in vitro studies showed that TCKP1 significantly enhanced the production of IFN-α, and reduced the level of HBV antigens and HBV DNA in the supernatants of HepG2.2.15 cells in a dose-dependent manner with low cytotoxicity. The result of the study on the HBV transgenic mice further revealed that TCKP1 significantly decreased the level of transaminases, HBsAg, HBeAg, and HBV DNA in the serum, as well as HBsAg, HBeAg, HBV DNA, and HBV RNA in the liver of HBV transgenic (HBV-Tg) mice. Furthermore, TCKP1 exhibited equivalent inhibitory effect with the positive control tenofovir alafenamide (TAF) on the markers above except for HBV DNA even in low dosage in a mouse model. However, the TCKP1 high-dose group displayed stronger inhibition of transaminases and liver HBsAg, HBeAg, and HBV RNA when compared with those of TAF. Meanwhile, inflammation of the liver was, by pathological observation, relieved in a dose-dependent manner after being treated with TCKP1. In addition, elevated levels of interleukin-12 (IL-12) and interferon γ (IFN-γ), and reduced level of interleukin-4 (IL-4) in the serum were observed, indicating that the anti-HBV effect of TCKP1 was achieved by potentiating immunocyte function and regulating the balance of Th1/Th2 cytokines.

Effect of renin-angiotensin-aldosterone system inhibitors on all-cause mortality and major cardiovascular events in patients with diabetes: A meta-analysis focusing on the number needed to treat and minimal clinical effect.

AIMS: To assess the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) separately to prevent all-cause mortality, myocardial infarction (MI), stroke and heart failure (HF) in patients with diabetes considering the number needed to treat (NNT) and minimal clinical effect (MCE). METHODS: Data from 17 morbidity-mortality trials in patients with diabetes were used to calculate NNTs and evaluate MCE to prevent all-cause mortality, myocardial infarction, stroke, and heart failure. RESULTS: A total of 17 trials involving 42,037 patients were included in this meta-analysis. Mean follow-up was 3.7 years. ACEIs significantly reduced the risk of all-cause mortality, MI and HF; the corresponding mean NNTBs were 48, 62 and 78, respectively, but ARBs were only associated with a reduction in heart failure. The clinical significance assessment of the included trials indicated that most of the statistically significant trial results had no definitive clinical significance, and only some of them had possible clinical significance. CONCLUSIONS: Among patients with diabetes, ACEIs reduced all-cause mortality, MI and HF, whereas ARBs could only prevent HF. However, none of the results of these trials had clear clinical significance, and most had only possible clinical significance.

Enrichment and Quantitative Determination of Free 3,5- Diiodothyronine, 3',5'-Diiodothyronine, and 3,5-Diiodothyronamine in Human Serum of Thyroid Cancer by Covalent Organic Hyper Cross-linked Poly-ionic Liquid.

The incidence of thyroid cancer is increasing worldwide. So far, still no non-invasive clinical test biomarkers were developed for the diagnosis of thyroid cancer. The diiodothyronines (T2s) are precursors and metabolites of thyroid hormone (T4). Some reports predict that T2s may be associated with several thyroid diseases, especially the thyroid cancer. Detecting free T2s in human serum may help the diagnosis of thyroid cancer. However, few works have reported the detection of T2s due to their trace amounts. Here we developed a novel hyper organic cross-linked poly ionic liquid (PIL) material for the enrichment of three main compounds in T2s family, including 3,5- diiodothyronine (3,5-T2), 3',5'-diiodothyronine (3',5'-T2), and 3,5-diiodothyronamine (3,5-T2AM). This PIL material provided specific enrichment superiority for three T2s. After enrichment, the signal intensity of 3,5-T2, 3',5'-T2, and 3,5-T2AM increased 14, 132 and 1.6 folds, respectively, with LOQ of 76, 87, and 107 fM, respectively. Finally, we successfully applied PIL material coupled with HPLC-ESI-MS/MS in enrichment and quantitative determination of free 3,5-T2, 3',5'-T2, and 3,5-T2AM in human serum of 45 thyroid cancer patients and 15 healthy people. We also used free thyroid hormone (FT4) as the calibration reference to eliminate individual differences. We found that the levels of 3,5-T2 (P < 0.001), and 3',5'-T2 (P = 0.001) in patients with thyroid cancer were significantly higher than those in healthy people. Additionally, we further investigated the power of different T2 thyroid hormones divided FT4 to classify thyroid cancer patients and healthy people. And 3,5-T2/FT4 had the highest classification performance for discriminating thyroid cancer patients from healthy people at certain threshold, indicating that 3,5-T2/FT4 in human serum can act as potential biomarkers for "non-invasive" clinical diagnosis of thyroid cancer.

Prognostic effects of the expression of inhibitor of DNA-binding family members on patients with lung adenocarcinoma.

The basic helix-loop-helix (bHLH) transcription factors are negatively regulated by inhibitor of DNA-binding (ID) proteins. Several studies have demonstrated that ID family proteins are dysregulated in a variety of cancer types, including in lung adenocarcinoma (LUAD). In current study, the prognostic value of ID family members was evaluated by investigating publicly accessible databases, including Oncomine, Kaplan-Meier plotter, UALCAN and the Human Protein Atlas. It was observed that the mRNA expression of all ID members was downregulated in LUAD tumor tissues compared with those in normal tissues according to the Oncomine and UALCAN databases. Additionally, increased mRNA expression levels of ID2 and ID1 were associated with improved and poorer survival time, respectively. Notably, ID3 and ID4 expression was not associated with survival in patients with LUAD. At the protein level, high ID2 significantly predicted an improved survival outcome while high ID1 is associated with shorter survival time. Thus, the results indicate that the ID proteins, particularly ID2, exhibit significant prognostic value in LUAD. More studies are required to elucidate the underlying molecular mechanisms behind the role of the ID family in the development of LUAD.