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This research utilized the outputs from three models of the Coupled Model Intercomparison Project Phase 6 (CMIP6), specifically CanESM5, GFDL-ESM4, and IPSL-CM6A-LR. These models were used under the SSP1-2.6 and SSP5-8.5 scenarios, along with the SPI and SPEI, to assess the impacts of climate change on drought in Iran. The results indicated that the average annual precipitation will increase under some scenarios and decrease under others in the near future (2022-2050). In the distant future (2051-2100), the average annual precipitation will increase in all states by 8-115 mm. The average minimum and maximum temperature will increase by up to 4.85 ℃ and 4.9 ℃, respectively in all states except for G2S1. The results suggest that severe droughts are anticipated across Iran, with Cluster 5 expected to experience the longest and most severe drought, lasting 6 years with a severity index of 85 according to the SPI index. Climate change is projected to amplify drought severity, particularly in central and eastern Iran. The SPEI analysis confirms that drought conditions will worsen in the future, with southeastern Iran projected to face the most severe drought lasting 20 years. Climate change is expected to extend drought durations and increase severity, posing significant challenges to water management in Iran., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a progressive brain disorder characterized by the ongoing decline of brain functions. Studies have revealed the detrimental effects of hyperphosphorylated tau (p-tau) protein fibrils in AD pathogenesis, highlighting the importance of this factor in the early-stage detection of AD conditions. We designed an electrochemical immunosensor for quantitative detection of the cis conformation of the p-tau protein (cis-p-tau) employing platinum nanoparticles (Pt NPs) supported on zeolitic imidazolate frameworks (ZIF) for modifying the glassy carbon electrode (GCE) surface. Under optimum conditions, the immunosensor selectively and sensitively detected cis-p-tau within the broad linear range of 1 fg mL -1 to 10 ng mL -1 and the low limit of detection (LOD) of 1 fg mL -1 with desired reproducibility and stability. Furthermore, the fabricated immunosensor's performance was examined for the cis-p-tau analysis in the serum of AD patients, indicating its accuracy and feasibility for real-sample analysis. Notably, this is the first application of Pt@ZIF-8 nanocomposite in fabricating a valid immunosensor for selective cis-p-tau detection, even in the presence of trans-p-tau. It is worth mentioning that the enzyme-linked immunosorbent assay (ELISA) reference technique is not able to evaluate pico- or femtomolar concentrations of cis-p-tau, making the fabricated immunosensor superior for early-stage measurement and screening of AD., (© 2023. The Author(s).)

Triple-negative breast cancers (TNBCs) are aggressive forms of breast cancer and tend to grow and spread more quickly than most other types of breast cancer. TNBCs can neither be targeted by hormonal therapies nor the antibody trastuzumab that targets the HER2 protein. There are urgent unmet medical needs to develop targeted drugs for TNBCs. We identified a small molecule NSC260594 from the NCI diversity set IV compound library. NSC260594 exhibited dramatic cytotoxicity in multiple TNBCs in a dose-and time-dependent manner. NSC260594 inhibited the Myeloid cell leukemia-1 (Mcl-1) expression through downregulation of Wnt signaling proteins. Consistent with this, NSC260594 treatment increased apoptosis, which was confirmed by using an Annexin-V/PI assay. Interestingly, NSC260594 treatment reduced the cancer stem cell (CSC) population in TNBCs. To make NSC260594 more clinically relevant, we treated NSC260594 with TNBC cell derived xenograft (CDX) mouse model, and with patient-derived xenograft (PDX) organoids. NSC260594 significantly suppressed MDA-MB-231 tumor growth in vivo, and furthermore, the combination treatment of NSC260594 and everolimus acted synergistically to decrease growth of TNBC PDX organoids. Together, we found that NSC260594 might serve as a lead compound for triple-negative breast cancer therapy through targeting Mcl-1., (© 2023. The Author(s).)

Cross-contamination of biological samples during handling and preparation, is a major issue in laboratory setups, leading to false-positives or false-negatives. Sample carryover residue in pipette tips contributes greatly to this issue. Most pipette tips on the market are manufactured with hydrophobic polymers that are able to repel high surface tension liquids, yet they lack in performance when low surface tension liquids and viscous fluids are involved. Moreover, hydrophobicity of pipette tips can result in hydrophobic adsorption of biomolecules, causing inaccuracies and loss in precision during pipetting. Here we propose the use of lubricant-infused surface (LIS) technology to achieve omniphobic properties in pipette tips. Using a versatile and simple design, the inner lumen of commercially available pipette tips was coated with a fluorosilane (FS) layer using chemical vapor deposition (CVD). The presence of FS groups on the tips is confirmed by x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) tests. After lubrication of the tips through a fluorinated lubricant, the omniphobicity and repellent behaviour of the tips drastically enhanced which are revealed via static and hysteresis contact angle measurements. The repellency of the lubricant-infused pipette tips against physical adsorption is investigated through pipetting a food coloring dye as well as human blood samples and are compared to the untreated tips. The results show significantly less amount carryover residue when the lubricant-infused tips are utilized compared to commercially available ones. We also demonstrate the lubricant-infused tips reduce bacteria contamination of the inner lumen by 3 to 6-log (over 99%, depending on the tip size) after pipetting up and down the bacteria solution., (© 2022. The Author(s).)

Acid-etching is one of the most popular processes for the surface treatment of dental implants. In this paper, acid-etching of commercially pure titanium (cpTi) in a 48% H 2 SO 4 solution is investigated. The etching process time (0-8 h) and solution temperature (25-90 °C) are assumed to be the most effective operational conditions to affect the surface roughness parameters such as arithmetical mean deviation of the assessed profile on the surface (R a ) and average of maximum peak to valley height of the surface over considered length profile (R z ), as well as weight loss (WL) of the dental implants in etching process. For the first time, three multilayer perceptron artificial neural network (MLP-ANN) with two hidden layers was optimized to predict R a , R z , and WL. MLP is a feedforward class of ANN and ANN model that involves computations and mathematics which simulate the human-brain processes. The ANN models can properly predict R a , R z , and WL variations during etching as a function of process temperature and time. Moreover, WL can be increased to achieve a high Ra. At WL = 0, R a of 0.5 μm is obtained, whereas R a increases to 2 μm at WL = 0.78 μg/cm 2 . Also, ANN model was fed into a nonlinear sorting genetic algorithm (NSGA-II) to establish the optimization process and the ability of this method has been proven to predict the optimized etching conditions., (© 2022. The Author(s).)

In the present article, we developed a highly sensitive label-free electrochemical immunosensor based on NiFe-layered double hydroxides (LDH)/reduced graphene oxide (rGO)/gold nanoparticles modified glassy carbon electrode for the determination of receptor tyrosine kinase-like orphan receptor (ROR)-1. In this electrochemical immunoassay platform, NiFe-LDH/rGO was used due to great electron mobility, high specific surface area and flexible structures, while Au nanoparticles were prepared and coated on the modified electrodes to improve the detection sensitivity and ROR1 antibody immobilizing (ROR1Ab). The modification procedure was approved by using cyclic voltammetry and differential pulse voltammetry based on the response of peak current to the step by step modifications. Under optimum conditions, the experimental results showed that the immunosensor revealed a sensitive response to ROR1 in the range of 0.01-1 pg mL -1 , and with a lower limit of quantification of 10 attogram/mL (10 ag mL -1 ). Furthermore, the designed immunosensor was applied for the analysis of ROR1 in several serum samples of chronic lymphocytic leukemia suffering patients with acceptable results, and it also exhibited good selectivity, reproducibility and stability., (© 2021. The Author(s).)

Dyslipidemia, a major risk factor for cardiovascular diseases, has become a global issue. Due to the variations in the prevalence of dyslipidemia, this study aimed to evaluate dyslipidemia and its associated factors in women of the Bandare-Kong Cohort Study (BKNCD). This study was conducted on women from the population-based BKNCD, as part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). Sociodemographic data, medical history, and anthropometric indices were collected. Dyslipidemia was defined as any lipid abnormality including low-density lipoprotein (LDL) ≥ 160, total cholesterol (TC) ≥ 240, high-density lipoprotein (HDL) < 40, or triglyceride > 200 mg/dl. From the 2223 women in this study (mean age: 48.28 ± 9.26 years), dyslipidemia was observed in 851 (38.3%). High TC was the most common lipid abnormality (18.5%) followed by high LDL (17.7%). Dyslipidemia was most prevalent among women aged 55-70 years, the married, those with < 6 years of education, the unemployed, the overweight or obese, with low socioeconomic status, diabetes, hypertension, and high waist circumference, those using the hookah and living in urban areas. Logistic regression revealed that women with high waist-to-hip ratio (WHR) (OR = 2.22, 95% CI 1.60-3.08), those aged 45-54 years (OR = 1.34, 95% CI 1.07-1.68) and 55-70 years (OR = 1.33, 95% CI 1.03-1.72), and those living in urban areas (OR = 1.35, 95% CI 1.05-1.73) were at significantly increased risk of dyslipidemia. In addition, the results were confirmed using deep neural network models. Dyslipidemia was highly prevalent in Iranian women in the southern coastal region. Central obesity, age over 45 years, and living in urban areas appear to be relatively significant risk factors for dyslipidemia among women.

A gravity current in a channel at the presence of a triangular obstacle was investigated using LES simulation and the Eulerian approach. The Saffman-Mei equation was also applied to examine the effect of shear-induced lift force on particle deposition. To this end, particles were considered as Lagrangian markers and injected into gravity current. It is important to keep in mind that the interaction between the gravity current and particles was treated as a one-way coupling. The results show that shear-induced lift force prevents particles to deposit at the entrance of channel, where the velocity gradient is high. Furthermore, a reduction in the rate of sediment deposition can be seen again in the vicinity of obstacle due to high velocity gradient. The important result is that the shear-induced lift force has an important role in the cases with considerable velocity gradient in quasi-steady flows and this force can affect the pattern of sedimentation over time. Q criterion is utilized to depict the vortical structures of flow. Vortical structures with larger diameter, that indicate stronger vortexes, has been seen in various sections of channel, especially in the region near the obstacle due to the presence of obstacle.

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC. In this report, we show that dacomitinib, a pan-ErbB receptor inhibitor, diminished growth, clonogenic potential, anoikis resistance and induced apoptotic cell death in therapy-resistant EOC cells. Dacominitib inhibited PLK1-FOXM1 signalling pathway and its down-stream targets Aurora kinase B and survivin. Moreover, dacomitinib attenuated migration and invasion of the EOC cells and reduced expression of epithelial-to-mesenchymal transition (EMT) markers ZEB1, ZEB2 and CDH2 (which encodes N-cadherin). Conversely, the anti-tumour activity of single-targeted ErbB agents including cetuximab (a ligand-blocking anti-EGFR mAb), transtuzumab (anti-HER2 mAb), H3.105.5 (anti-HER3 mAb) and erlotinib (EGFR small-molecule tyrosine kinase inhibitor) were marginal. Our results provide a rationale for further investigation on the therapeutic potential of dacomitinib in treatment of the chemoresistant EOC.

Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones. Overexpression of VEGFR2 correlated with resistance to cisplatin and combination with VEGFR2-inhibitor apatinib synergistically increased cisplatin sensitivity. Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. Tivozanib decreased invasive potential of these cells, concomitant with reduction of intercellular adhesion molecule-1 (ICAM-1) and diminishing the enzymatic activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumour effects of EGFR-directed therapies including erlotinib. These findings suggest that the VEGF pathway has potential as a therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumour efficacy and circumvent resistance to EGFR-directed therapies.

Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM.