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Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC 50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management., (© 2024. Controlled Release Society.)

Improperly managed wastes that have been dumped in landfills over the years pose various challenges, but they also offer potential benefits. The feasibility of recycling such waste depends on the type of wastes, the condition of dumpsites, and the technology implemented for disposal. The selection of an alternative waste disposal method from the many available options for dumpsite remediation is a complex decision-making process among experts. The primary aim of this study is to assist in an extended multi-criteria decision-making (MCDM) method to reduce complexity in the proposed dumpsite remediation problem influenced by multiple criteria and to identify the optimal waste disposal method. Data uncertainties are managed with the proposed Fermatean fuzzy preference scale, and the importance of all socio-economic criteria is assessed using the full consistency method (FUCOM). The final ranking results of the weighted aggregated sum product assessment (WASPAS) method identify that the Waste-to-Energy (WtE) process could play a significant role in the disposal of land-filled unprocessed wastes, promoting sustainable waste management. Meanwhile, the methodology explores the idea that financial and logistical constraints may limit the feasibility of large-scale recycling efforts. This combination of environmental science and decision science addresses real-world challenges, helping municipal solid waste management authorities implement sustainable waste management practices., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper aims to investigate the effect of leachate on the geotechnical parameters and the cracking behavior of compacted clay liners (CCLs) containing different percentages of polypropylene fibers. Accordingly, 200 compacted clay samples were reinforced with different percentages of fiber contents (FC) (i.e., 0, 0.5, 0.75, and 1%) and prepared with water or leachate to conduct different laboratory tests. First, the physical properties of the clay were determined. Then, the shear strength parameters (i.e., cohesion and friction angle), unconfined compressive strength, and the hydraulic permeability were determined subjected to water or leachate. Notably, the cracking behavior was modeled using visual images of the samples. The leachate increased desiccation cracks in the natural soil from 0.425 to nearly 1.111%. However, the addition of 0.5% (in the case of water) and 1% (in the case of leachate) fiber to the soil reduced the surface desiccation cracks in clay liners to about 0.185 and 0.352%, respectively. In both water- or leachate-prepared samples, the addition of fibers significantly increased the cohesion and friction angle. The shear strengths of the unreinforced leachate-prepared samples were lower than those of the water-prepared samples. The shear strength and unconfined compressive strength of all specimens increased with increasing fiber percentage. The presence of fibers in all samples caused more ductile behavior. The required amount of energy to achieve the maximum strength in the samples increased with increasing FC. By increasing the percentage of fibers, the permeability of the natural soil and the leachate-prepared samples increased. However, the highest permeability was observed in the leachate-prepared samples containing 1% fibers of 8.3 × 10 -10  m/s, which is less than 10 -9  m/s (maximum allowable permeability for clay liners). Finally, the obtained results were satisfactorily confirmed by scanning electron microscopy (SEM) analysis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The rate of infertility has globally increased in recent years for a variety of reasons. One of the main causes of infertility in men is azoospermia that is defined by the absence of sperm in the ejaculate and classified into two categories: obstructive azoospermia and non-obstructive azoospermia. In non-obstructive azoospermia, genital ducts are not obstructed, but the testicles do not produce sperm at all, due to various reasons. Non-obstructive azoospermia in most cases has no therapeutic options other than assisted reproductive techniques, which in most cases require sperm donors. Here we discuss cell-based therapy approaches to restore fertility in men with non-obstructive azoospermia including cell-based therapies of non-obstructive azoospermia using regenerative medicine and cell-based therapies of non-obstructive azoospermia by paracrine and anti-inflammatory pathway, technical and ethical challenges for using different cell sources and alternative options will be described, and then the more effectual approaches will be mentioned as future trends., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

This paper studies the problem of detection of dental diseases. Dental problems affect the vast majority of the world's population. Caries, RCT (Root Canal Treatment), Abscess, Bone Loss, and missing teeth are some of the most common dental conditions that affect people of all ages all over the world. Delayed or incorrect diagnosis may result in mistreatment, affecting not only an individual's oral health but also his or her overall health, thereby making it an important research area in medicine and engineering. We propose a pipelined Deep Neural Network (DNN) approach to detect healthy and non-healthy periapical dental X-ray images. Even a minor enhancement or improvement in existing techniques can go a long way in providing significant health benefits in the medical field. This paper has made a successful attempt to contribute a different type of pipelined approach using AlexNet in this regard. The approach is trained on a large dataset of 16,000 dental X-ray images, correctly identifying healthy and non-healthy X-ray images. We use an optimized Convolutional Neural Networks and three state-of-the-art DNN models, namely Res-Net-18, ResNet-34, and AlexNet for disease classification. In our study, the AlexNet model outperforms the other models with an accuracy of 0.852. The precision, recall and F1 scores of AlexNet also surpass the other models with a score of 0.850 across all metrics. The area under ROC curve also signifies that both the false-positive rate and false-negative rate are low. We conclude that even with a big data set and raw X-ray pictures, the AlexNet model generalizes effectively to previously unseen data and can aid in the diagnosis of a variety of dental diseases., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Pressure ulcers (PUs), a result of ischemic reperfusion (IR) injuries, are prevalent skin problems which show refractoriness against standard therapeutic approaches. Besides, scar formation is a critical complication of ulcers that affects functionality and the skin's cosmetic aspect. The current study aimed to investigate the effects of placenta-derived human amniotic epithelial cells (hAECs), as important agents of regenerative medicine and stem cell therapy, on accelerating the healing of IR ulcers in mice. We also evaluated the effects of these cells on reducing the TGFβ-induced scar formation., Methods: Male Balb/c mice at the age of 6-8 weeks were subjected to three IR cycles. Afterward, the mice were divided into three experimental groups (n = 6 per group), including the control group, vehicle group, and hAECs treatment group. Mice of the treatment group received 100 μL of fresh hAECs 1 × 10 6 cell/ml suspension in PBS. Afterward, mice were assessed by histological, stereological, molecular, and western blotting techniques at 3, 7, 14, and 21 days after wounding., Results: The histological and stereological results showed the most diminutive scar formation and better healing in the hAECs treated group compared to control group. Furthermore, our results demonstrated that the expression level of Col1A1 on days 3, 14, and 21 in the hAECs treated group was significantly lower than control. Additionally, injection of hAECs significantly reduced the expression level of Col3A1 on days 3, 7, and 21 while increased Col3A1 on the day 14. Otherwise, in the hAECs treated group, the expression levels of VEGFA on days 7 and 14 were higher, which showed that hAECs could promote angiogenesis and wound healing. Also, cell therapy significantly lowered the protein levels of TGF-β1 on day 14, while the protein level of TGF-β3 on day 14 was significantly higher. This data could demonstrate the role of hAECs in scar reduction in IR wounds., Conclusion: These results suggest that hAECs can promote re-epithelialization and wound closure in an animal model of PU. They also reduced scar formation during wound healing by reducing the expression of TGF-β1/ TGF-β3 ratio., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a growing interest in designing a nanocarrier containing an EGFR targeting affibody to direct toward cancer cells. Here, cytolysin A was cloned at the N-terminus of Z EGFR:1907 affibody to guarantee its surface presentation on the OMVs while targeting the epidermal growth factor receptors (EGFRs). A separate construct including a fusogenic peptide (GALA) was also designed for the endosomal escape of the nanocarrier. Binding of the two constructs ClyA-affi EGFR and ClyA-affi EGFR -GALA to domain III of EGFR was investigated using molecular docking and molecular dynamic simulations. The higher stability of the ClyA-affi EGFR -GALA/EGFR as compared to the ClyA-affi EGFR /EGFR complex was evident. The ClyA-affi EGFR -GALA structure showed a higher RMSD during the first half of the simulation time implying a much less stable behavior. Plateau state of the radius of gyration plot of ClyA-affi EGFR -GALA confirmed a well-folded structure in the presence of the GALA sequence. Solvent accessible surface area for both proteins was in the same range. The data obtained from hydrogen bond analysis revealed a more equilibrated and stable form of the ClyA-affi EGFR -GALA structure upon interaction with EGFR. The data provided here was a requisite for our biological evaluation of the synthesized constructs as a component of a novel drug delivery system., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A new type of honeycomb structured UiO-66 metal-organic frameworks (MOF) was synthesized and amino functionalized followed by employing them to prepare mixed matrix membranes (MMM). The influences of dimethylformamide (DMF) and H 2 O/ethanol (70/30 wt.%) blend were firstly investigated on morphology, structure, and CO 2 /CH 4 separation efficiency of Pebax®1657 membranes. Based on the transmission electron microscopy (TEM) analysis, the synthesized MOF has 15 nm in diameter. DMF led to the formation of a more crystalline (based on X-ray diffraction (XRD) analysis) and more porous structure. Higher CO 2 permeability and CO 2 /CH 4 selectivity were observed as DMF was employed to fabricate neat membranes. Scanning electron microscopy (SEM) exhibited MOF agglomeration as the UiO-66 was used while the nanoparticle dispersion was enhanced when UiO-66-NH 2 was exploited. Fourier transform infrared spectroscopy (FTIR) confirmed the successful MOF incorporation into the MMMs. Ultimately, the gas separation experiments showed that CO 2 permeability was enhanced compared to the neat membrane by 44.7% and 49.4% as 10 wt.% UiO-66 and UiO-66-NH 2 were used, respectively. Moreover, the Pebax®1657-UiO-66-NH 2 MMMs exhibited 71.7% and 34.5% improvement in selectivity of CO 2 /N 2 and CO 2 /CH 4 , respectively, owing to enhancing CO 2 -OH interactions while the CO 2 /O 2 was declined by 8.8%.

Pro-apoptotic peptides have attracted much attention as promising anticancer agents due to their high activity. However, poor cellular uptake of the peptides is often associated with limited therapeutic application. Cell-penetrating homing peptides (CPHPs) were found to increase cell internalization as well as anticancer efficacy of the peptide conjugates. In this study, we developed a novel recombinant fusion protein composed of sIL-24 peptide as a pro-apoptotic moiety and asparagine-glycine-arginine (NGR) motif as a CD13-targeting CPHP component. In silico analysis demonstrated that flexible GGGGS linker provided the best structure and stability for our designed fusion protein. Cell adhesion experiments showed a significant binding affinity toward high CD13-expressing cells (U937 and A549) for NGR-sIL-24. Moreover, confocal microscopy revealed that NGR strongly facilitated the binding and cellular uptake of sIL-24 in U937 and A549 cancer cells. NGR-sIL-24 treatment markedly inhibited the growth of U937 and A549 cancer cells in a dose and time-dependent manner, without affecting the normal cell line MRC-5. Flow cytometric analysis and Hoechst 33342 staining exhibited potent apoptosis induction in U937 and A549 cells treated with NGR-sIL-24. Further mechanism elucidation uncovered that apoptotic death promoted by NGR-sIL-24 was attributed to upregulation of BiP/GRP78, Bax/Bcl-2, GADD34, cytochrome c release, and cleavage of caspase-3, suggesting NGR-sIL-24 penetration into cancerous cells and subsequent apoptosis induction, mainly through endoplasmic reticulum (ER) stress-dependent and mitochondria-dependent signaling pathways. Our results indicate that the designed recombinant fusion protein NGR-sIL-24 may serve as a potential targeted therapy agent for cancers with high expression of CD13.

Purpose: Mutagen X is a hazardous by-product of disinfection by chlorine, which is responsible for most of the mutagenicity in chlorinated drinking water. It has the cancer potency value of 100-fold higher than bromodichloromethane and 6000-fold higher than chloroform, In this study, Mutagen X was removed from aqueous media by a thermally reduced graphene oxide bonded on the surface of amino-functionalized sand particles., Method: A Box-Behnken design was applied to optimize the adsorption process. Characterization of the adsorbent and graphene oxide was accomplished using scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Raman analysis. The effects of three independent parameters, including initial concentration (20-200 μg L -1 ), temperature (5-30 °C), and adsorbent dose (2-80 g L -1 ) were examined using batch experiments., Results: Characterization results confirmed that the graphene oxide was successfully coated on the surface of sand particles. Regression analysis of experimental results showed a great fit with a quadratic polynomial model with the R 2  = 0.999. Optimum conditions (initial concentration: 20 μg L -1 , temperature: 30 °C, and adsorbent dose: 80 g L -1 ) with the desirability of 1.0 resulted in the minimum residual concentration of Mutagen X (2 μg L -1 ). Equilibrium study results depicted that the experimental data were fitted well to the Freundlich and UT isotherm models., Competing Interests: Conflict of interestThere is no conflict of interest., (© Springer Nature Switzerland AG 2019.)

Coronary artery disease is the leading cause of death among the men and women. One of the most suitable treatments for this problem is balloon angioplasty with stenting. Functionally graded material (FGM) stents have shown suitable mechanical behavior in simulations. While their deformation was superior to uniform materials, the study was aimed at finding the most suitable configuration to reach the optimum performance. A combination of finite element method (FEM) and optimization algorithm have been used to fulfil this objective. To do that, three different conditions have been investigated in a Palmaz-Schatz geometry, where in the first and second ones the stent was a combination of steel and CoCr alloy (L605), and the third condition was a combination of CoCr alloy (L605) and CoCr alloy (F562). In the first and third conditions, dogboning was the objective function, but in the second condition a non-uniform deformation indicator was chosen as the objective function. In all three conditions the heterogeneous index was the control variable. The stent in the third condition showed a poor performance. While in the steel/CoCr alloy (L605) stents the heterogeneous index of 0.374 showed the lowest maximum dogboning, the heterogeneous index of 5 had more uniform deformation. Overall due to the lower dogboning of the steel/CoCr alloy (L605) stent with heterogeneous index of 0.374, this stent is recommended as the optimum stent in this geometrical configuration.

The presence of contaminants of emerging concern (CECs) such as pharmaceuticals and personal care products (PPCPs), endocrine-disrupting compounds (EDCs), flame retardants (FRs), pesticides, and artificial sweeteners (ASWs) in the aquatic environments remains a major challenge to the environment and human health. In this review, the classification and occurrence of emerging contaminants in aquatic environments were discussed in detail. It is well documented that CECs are susceptible to poor removal during the conventional wastewater treatment plants, which introduce them back to the environment ranging from nanogram per liter (e.g., carbamazepine) up to milligram per liter (e.g., acesulfame) concentration level. Meanwhile, a deep insight into the application of advanced oxidation processes (AOPs) on mitigation of the CECs from aquatic environment was presented. In this regard, the utilization of various treatment technologies based on AOPs including ozonation, Fenton processes, sonochemical, and TiO 2 heterogeneous photocatalysis was reviewed. Additionally, some innovations (e.g., visible light heterogeneous photocatalysis, electro-Fenton) concerning the AOPs and the combined utilization of AOPs (e.g., sono-Fenton) were documented.

Based on radial functionally graded biomaterials and inspired by the geometry of a real aorta blood vessel, a new model was proposed to fabricate the artificial blood vessels. A finite element analyzer is employed to reach the optimal and proper material properties while earlier, it was validated by two famous theories, i.e., the first shear deformation and the plane elasticity. First, the geometry of a real ascending aorta part was simulated and then solved under the axially varying blood pressure and other real and actual conditions. Since the construction of artificial blood vessels just similar to the natural one is impossible, it was tried to find the best substitutes for other materials. Due to the significant properties of functionally graded biomaterials in the reduction in sudden changes of stress and deformation, these types of materials were selected and studied. Two types of conventional single-sided and an efficient double-sided radial functionally graded vessel were proposed and simulated. The elastic behaviors of proposed vessels were obtained and compared to ones previously attained from the real vessel. The results show that all the desired behaviors cannot be achieved by using a conventional single-sided radial FG vessel. Instead and as a conjecture, a smart double-sided radial FG biomaterial is suggested. Fortunately, the proposed material can meet all the desired goals and satisfy all of the indices simultaneously.

Osteoporosis (OP) increases vertebral fragility as a result of the biomechanical effects of diminished bone structure and composition. This study has aimed to assess the effects of pulsed wave low-level laser therapy (PW LLLT) on cancellous bone strength of an ovariectomized (OVX-d) experimental rat model and a glucocorticoid-induced OP (GIOP) experimental rat model. There were four OVX-d groups and four dexamethasone-treated groups. A group of healthy rats was used for baseline evaluations. The OVX-d rats were further subdivided into the following groups: control rats with OP, OVX-d rats that received alendronate, OVX-d rats treated with PW LLLT, and OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone and were divided into four groups: control, alendronate-treated rats, laser-treated rats, and laser-treated rats with concomitant administration of alendronate. PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) was performed on the spinal processes of the T12, L1, L2, and L3 vertebras. We extracted the L1 vertebrae and submitted them to a mechanical compression test. Biomechanical test findings showed positive effects of the PW LLLT and alendronate administration on increasing bending stiffness and maximum force of the osteoporotic bones compared to the healthy group. However, laser treatment of OVA-d rats significantly increased stress high load compared to OVA-d control rats. PW LLLT preserved the cancellous (trabecular) bone of vertebra against the detrimental effects of OV-induced OP on bone strength in rats compared to control OV rats.

Osteoporosis (OP) is a disease which causes bone loss and fractures, leading to severe pain and deformity. This study has aimed to assess the effects of pulsed wave low-level laser therapy (PW LLLT) on cortical bone in two experimental models of OP in rats. There were four ovariectomized (OVX-d) groups and four dexamethasone-treated groups. The healthy group were considered for baseline evaluations. At 14 weeks following ovariectomy, the OVX-d rats were further subdivided into the following: control rats with OP, OVX-d rats that received alendronate (1 mg/kg), OVX-d rats treated with LLLT, and OVX-d rats treated with alendronate and LLLT. The remaining rats received dexamethasone for 5 weeks and were divided into four groups: control, alendronate-treated rats (1 mg/kg), laser-treated rats, and laser-treated rats with concomitant administration of alendronate. The rats received alendronate for 30 days. LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) was performed on the tibias three times per week for 8 weeks. After 8 weeks, tibias were extracted and submitted to a three-point bending test. PW LLLT did not increase the biomechanical parameters of osteoporotic bones compared to controls and healthy rats. PW LLLT associated with alendronate treatment significantly increased stress high load in OVX-d rats compared to the healthy group. PW LLLT at the current study parameters failed to cause beneficial biomechanical effects in the examined osteoporotic cortical bones. PW LLLT associated with alendronate treatment produced a more remarkable effect on bone strength in the ovariectomized induced OP rat model.

ATM protein kinase plays a critical role in maintaining genome integrity by activating a biochemical chain reaction that in turn leads to cell cycle checkpoint activation and repair of DNA damage. Cyclin D1 acts in regulating the G1 phase of the cell cycle. Experimental and clinical studies suggest them to be involved in transformation and tumour progression. To elucidate the role of ATM and cyclin D1 expression in sporadic breast cancer, we investigated the possible link between their RNA expression levels in ductal carcinoma and normal adjacent versus normal breast tissues measured by Taqman real-time PCR in 119 breast tissues. Results showed that cyclin D1 over-expressed in 51.4% of breast tumours, whereas ATM expression was down regulated in 55% of breast tumours compared to both normal adjacent and normal controls (P ≤ 0.01). Cyclin D1 expression in adjacent normal and normal tissues was not significantly differed, whereas ATM expression in normal adjacent was lower than normal control (P ≤ 0.01). Over-expression of cyclin D1 correlated with ER(+) and/or PR(+) (oestrogen/progesterone receptor) status, whereas it mostly under-expressed in HER2(+) (human epidermal growth factor 2) tumours. ATM under-expression was more observed in triple-negative tumours (ER(-), PR(-) and HER2(-)). Our results indicated that reduced expression of the ATM and aberrant cyclin D1 expressions may contribute to the development and/or malignant progression of breast carcinomas also the latter could be involved in the regulation of hormone sensitivity associated with ER and PR.