Cancer is a fatal disease that is responsible for approximately 10 million deaths per year. This is due to complex mechanisms inside tumor microenvironment (TME) such as elevated GSH and hypoxia which reduce the curative effects of cancer therapies. The present review explores different approaches can target glutathione metabolic enzymes or their regulators to deplete GSH in cancer as well as overviewing role of natural compounds in disrupting GSH metabolism. Nanomedicine for many years was able to improve the efficacy and delivery of drugs using various forms of functionalized nanocarriers. Therefore, we summarize some of smart nanocarriers for chemotherapy, PDT, and SDT wither alone or combination used to reduce GSH level in TME with simultaneous rise of reactive oxygen species (ROS) levels. Furthermore, overcoming hypoxia and improving PDT could be accomplished by inhibiting hypoxia-induced factor – 1 (HIF-1), which is upregulated in TME, or using nanocarriers that deliver oxygen. Because SDT was able to replace PDT due to its deep penetration into tissues, its effectiveness was increased based on catalytic nanomedicine, which modulates TME via the efficient catalytic properties of nanoparticles. The current review offered future perspectives on the challenges, as well as potential solutions from various developed multifunctional nanoparticulate drug delivery systems to overcome elevated levels of GSH and hypoxia in TME.

The current study aims to explore the tensile fracture mechanism and thermo-mechanical efficiency of polyamide-6 (PA6) reinforced with titanium dioxide (TiO2) and multiwalled carbon nanotubes (MWCNTs). The uniform dispersion of the MWCNTs and appreciable interfacing between PA6, TiO2, and MWCNTs were revealed in the fractography figures. The crystallization temperature and degree of crystallinity have been enhanced by the addition of nanoparticles to the PA6 matrix. Young?s modulus, tensile strength, and Charpy impact strength improved proportionally concerning reinforcement content. The essential work of fracture (EWF) method was applied to evaluate the toughening and fracture behavior of PA6 hybrid systems. Considerable improvement (+60.6%) in the EWF of PA6?TiO2?MWCNT nanocomposites was observed at 4 wt.% CNT and 2 wt.% TiO2. Limiting oxygen index (LOI) findings demonstrate that a polymer with a combination containing titanium dioxide and multiwalled carbon nanotubes has a highly substantial retardant influence. As a result, the TiO2?CNT combination acts as a synergist filler, offering versatile PA6 composite products.

Upregulation of ATP binding cassette (ABC) transporter efflux pumps (i.e. P-glycoprotein, P-gp) can impart multidrug resistance, rendering many chemotherapeutics ineffective and seriously limiting treatment regimes. While ABC transporters remain an attractive target for therapeutic intervention, the development of clinically useful small-molecule inhibitors has proved challenging. In this report, we describe the structure–activity relationship (SAR) analysis of a newly discovered P-gp inhibitory pharmacophore, phenylpropanoid piperazine chrysosporazines, produced by co-isolated marine-derived fungi. In the absence of any total syntheses, we apply an innovative precursor-directed biosynthesis strategy that successfully repurposed fungal biosynthetic output, allowing us to isolate, characterize, and identify the structurally diverse neochrysosporazines A–Q. SAR analysis utilizing all known (and new) neochrysosporazines, chrysosporazines, and azachrysosporazines, plus semi-synthetic analogues, established the key structure requirements for the P-gp inhibitory pharmacophore, and, in addition, identified non-essential sites that allow for the design of affinity and other conjugated probes.

Understanding the genetic mechanisms underlying milk production traits contribute to improving the production potential of dairy animals. Long-chain acyl-CoA synthetase 1 (ACSL1) plays a key role in fatty acid metabolism and was highly expressed in the lactating mammary gland epithelial cells (MGECs). The objectives of the present study were to detect the polymorphisms within ACSL1 in Mediterranean buffalo, the genetic effects of these mutations on milk production traits, and understand the gene regulatory effects on MGECs. A total of twelve SNPs were identified by sequencing, including nine SNPs in the intronic region and three in the exonic region. Association analysis showed that nine SNPs were associated with one or more traits. Two haplotype blocks were identified, and among these haplotypes, the individuals carrying the H2H2 haplotype in block 1 and H5H1 in block 2 were superior to those of other haplotypes in milk production traits. Immunohistological staining of ACSL1 in buffalo mammary gland tissue indicated its expression and localization in MGECs. Knockdown of ACSL1 inhibited cell growth, diminished MGEC lipid synthesis and triglyceride secretion, and downregulated CCND1, PPARγ, and FABP3 expression. The overexpression of ACSL1 promoted cell growth, enhanced the triglyceride secretion, and upregulated CCND1, PPARγ, SREBP1, and FABP3. ACSL1 was also involved in milk protein regulation as indicated by the decreased or increased β-casein concentration and CSN3 expression in the knockdown or overexpression group, respectively. In summary, our present study depicted that ACSL1 mutations were associated with buffalo milk production performance. This may be related to its positive regulation roles on MGEC growth, milk fat, and milk protein synthesis. The current study showed the potential of the ACSL1 gene as a candidate for milk production traits and provides a new understanding of the physiological mechanisms underlying milk production regulation.

MgSnN2 thin films were deposited by reactive magnetron co-sputtering on fused silica and silicon substrates. The properties of the films were determined as a function of the deposition temperature. Although the films exhibited a strong preferred orientation along the [002] direction, cumulative X-ray diffractograms at various χ angles evidenced that the deposited films crystallized in a wurtzite-like structure. Regardless of the substrate temperature during deposition, MgSnN2 films had a columnar microstructure. Mössbauer spectrometry and X-ray photoemission spectroscopy were used to extract the chemical environment of magnesium and tin atoms and to identify their oxidation states. Electrical properties were deduced from Hall effect measurements. An increase of the electron mobility was noticed at high deposition temperature. The optical band gap of MgSnN2 films increased from approx. 2.28 to 2.43 eV in the 300–500 °C range. The experimental optical properties of MgSnN2 films were compared to those obtained by ab initio calculations.

This work reports on the luminescence properties of cerium and samarium co-doped in yttrium–aluminum–garnet ceramic. Single and co-doped YAG nanocrystals have been prepared at different contents of Ce ions. The X-ray diffraction (XRD) confirms the formation of the crystallites and the phase purity. The ceramic has been fabricated by sintering using spark plasma sintering technique. It is found that the photoluminescence (PL) spectral features of ceramic sample are strongly dependent on the excitation wavelength. Broad emission band from Ce3+, is superimposed with the emission lines from Sm3+, thanks to significant spectral overlapping of their excitation lines. Consequently, the emitted color parameters can be widely controlled, as demonstrated from the chromaticity diagram. In addition, cathodoluminescence (CL) has been performed and evidenced the superimposed CL signal from both ions. Moreover, the time-resolved photoluminescence (TRPL) result indicates the influence of such spectral overlapping on the luminescence decay kinetics.

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Since their emergence, biodegradable polymers have revolutionized the biomedical engineering field. Their high biocompatibility, tailorability, versatility along with easy processability, highly nominated these biomaterials for fabricating biodegradable medical implants. The introduction of this biomaterial class led to an astounding change in the concept of the medical implants from traditionally being bioinert to the nowadays bioactive implants that are capable of not only stimulating certain biological responses but also delivering various drugs and bioactive molecules. In that light, this article will present the frontiers of the world of biodegradable polymers and their indispensable applications in the biomedical field.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.