Premature Degradation Research Articles

A data-driven approach for predicting interface bond strength between corroded reinforcement and concrete

The deterioration of interface bond strength of reinforcement and concrete in a corrosive environment is the primary cause of premature degradation that affects reinforced concrete structures. Thus, it is crucial to establish a highly reliable bond strength model of corroded reinforced concrete. For this study, we collected data from previous experimental investigations on the interface bond strength between corrosion reinforcement and concrete, and developed a BP-ANN model on the interface bond strength based on a data-driven approach. The model utilized input variables for instance corrosion level, reinforcement diameter, concrete cover to reinforcement diameter ratio, reinforcement diameter to bond length ratio, reinforcement yield strength and concrete compressive strength. The output target was interface bond strength, and the model was trained and tested by using 166 groups of pull-out test datas for corrosion reinforcements and concrete with varying corrosion rates. The outcomes demonstrate that the predictions of the BP-ANN model match well with actual values. Furthermore, the predictive efficiency for the BP-ANN model was verified by comparison of the predicted values with the actual values. A comparative analysis of the applicability and computational error of the BP-ANN model indicates that a data-driven approach to predict bond strength between reinforcement and concrete in an erosion environment has better prediction accuracy than the empirical or semi-empirical bond strength models used in previous studies. Additionally, a sensitivity analysis of the primary influencing factors on bond strength of corroded reinforced concrete is conducted, and it is quantitatively confirmed that the corrosion level was the most significant factor on bond strength, while the influence of reinforcement yield strength is comparatively small.

Gallic acid-functionalized soy protein-based multiple cross-linked hydrogel: Mechanism analysis, physicochemical properties, and digestive characteristics

Herein, carbodiimide hydrochloride/N-hydroxysuccinimide was used to mediate the grafting of gallic acid (GA) (0.005, 0.0015, and 0.025 wt%) with soybean protein isolate (SPI) in the preparation of SPI-GA conjugates and hydrogels. The modified materials were primarily joined via the CN bonds and exhibited excellent antioxidant properties. In addition, spectral analysis revealed that the grafting of GA increased the flexibility of the SPI structure. The SPI-GA hydrogel is fabricated through covalent/non-covalent cross-linking mechanisms, including Schiff base, Michael addition, and hydrogen bonding. Furthermore, the microstructure, rheological properties, thermal stability, and textural properties of the hydrogel were affected by the amount of GA grafted. The SPI-GA hydrogel exhibited the best performance when the amount of GA graft was 0.015 wt%. Furthermore, the tightly cross-linked structure of SPI-GA prevented premature degradation of the protein by pepsin. In conclusion, these capabilities provide numerous possibilities for the development of multifunctional and active substance delivery carriers.

Postmeiotic irregular anther1 (PIA1) is required for anther cuticle and pollen exine development in maize (Zea mays L.)

AbstractMale sterile lines are valuable germplasm resources for hybrid seed production in maize (Zea mays L.). The structures of the anther cuticle and pollen exine are associated with male sterility. We obtained a completely male sterile mutant (postmeiotic irregular anther1, pia1), which has closed glumes and relatively small and wilted anthers (compared with the wild‐type control). Cytological analysis revealed the normal meiosis and premature tapetal degradation in pia1. Additionally, formation of the pia1 anther cuticle and Ubisch bodies was abnormal, and the pollen exine was discontinuous. Genetic analysis showed that the pia1 mutant was the result of a single recessive mutation of a nuclear gene. On the basis of fine mapping, PIA1 was mapped between the W07051 and W07124 molecular markers on chromosome 1. This region does not contain known genes associated with male sterility. Furthermore, transcriptome analysis indicated genes implicated in transmembrane transport, amino acid transmembrane transport, amino acid transport, and carboxylic acid transmembrane transport are differentially expressed in pia1 mutant anthers. The study findings suggest PIA1 is a novel regulator of anther cuticle and pollen exine development.

Addressing Nanovaccine Strategies for Tilapia.

Tilapia is the world's most extensively farmed species after carp. It is an attractive species for aquaculture as it grows quickly, reaching harvest size within six to seven months of production, and provides an important source of food and revenue for many low-income families, especially in low- to middle-income countries. The expansion of tilapia aquaculture has resulted in an intensification of farming systems, and this has been associated with increased disease outbreaks caused by various pathogens, mostly bacterial and viral agents. Vaccination is routinely used to control disease in higher-value finfish species, such as Atlantic salmon. At the same time, many tilapia farmers are often unwilling to vaccinate their fish by injection once the fish have been moved to their grow-out site. Alternative vaccination strategies are needed to help tilapia farmers accept and use vaccines. There is increasing interest in nanoparticle-based vaccines as alternative methods for delivering vaccines to fish, especially for oral and immersion administration. They can potentially improve vaccine efficacy through the controlled release of antigens, protecting antigens from premature proteolytic degradation in the gastric tract, and facilitating antigen uptake and processing by antigen-presenting cells. They can also allow targeted delivery of the vaccine at mucosal sites. This review provides a brief overview of the bacterial and viral diseases affecting tilapia aquaculture and vaccine strategies for farmed tilapia. It focuses on the use of nanovaccines to improve the acceptance and uptake of vaccines by tilapia farmers.

Modeling Sarcoglycanopathy in Danio rerio.

Sarcoglycanopathies, also known as limb girdle muscular dystrophy 3-6, are rare muscular dystrophies characterized, although heterogeneous, by high disability, with patients often wheelchair-bound by late adolescence and frequently developing respiratory and cardiac problems. These diseases are currently incurable, emphasizing the importance of effective treatment strategies and the necessity of animal models for drug screening and therapeutic verification. Using the CRISPR/Cas9 genome editing technique, we generated and characterized δ-sarcoglycan and β-sarcoglycan knockout zebrafish lines, which presented a progressive disease phenotype that worsened from a mild larval stage to distinct myopathic features in adulthood. By subjecting the knockout larvae to a viscous swimming medium, we were able to anticipate disease onset. The δ-SG knockout line was further exploited to demonstrate that a δ-SG missense mutant is a substrate for endoplasmic reticulum-associated degradation (ERAD), indicating premature degradation due to protein folding defects. In conclusion, our study underscores the utility of zebrafish in modeling sarcoglycanopathies through either gene knockout or future knock-in techniques. These novel zebrafish lines will not only enhance our understanding of the disease's pathogenic mechanisms, but will also serve as powerful tools for phenotype-based drug screening, ultimately contributing to the development of a cure for sarcoglycanopathies.

Experimental characterization of impact damage in foam-core sandwich structures using acoustic emission, optical scanning and X-ray computed tomography techniques

Sandwich structures used in transportation and energy industries are commonly subjected to low-velocity impact in the course of manufacturing, service and maintenance, which can lead to the premature degradation of structural stiffness and strength. A single non-destructive evaluation technique is often difficult to provide a comprehensive assessment on impact damage from online to offline and from visible to invisible. In the present study, acoustic emission (AE), three-dimensional (3D) optical scanning and X-ray computed tomography (CT) techniques are combined to provide a systematic approach for damage characterization of thick foam-core sandwich panels under low-velocity impact. In the tests, the mechanical responses such as force-time and force-displacement curves are obtained from the testing system. The AE technique is adopted to monitor damage initiation and evolution in situ; optical scanning and X-ray computed tomography techniques are used for off-line damage identification and quantification. The results show that the AE signal waveform stream, cumulative counts and cumulative energy correlate well with the mechanical responses of the sandwich panel under the low-velocity impact, enabling capture of valuable information for online damage monitoring. Unlike general cases, the AE signals generated from low-velocity impact are found to be presented in strong bursts of nearly coincident events in the short duration. Therefore, the distributions of AE amplitude and peak frequency between adjacent AE counts are extracted to study the different damage modes and damage mechanisms. The X-ray computed tomography images enable to precisely visualize the fracture behaviors of the PET foam-core inside the sandwich panel in a nondestructive fashion, which evidently supports the AE and optical scanning results. The study is anticipated to demonstrate effectiveness and capability of the proposed experimental methodology for damage detection and characterization on sandwiched composite structures subjected to impact loading.

Mad2 is dispensable for accurate chromosome segregation but becomes essential when oocytes are subjected to environmental stress.

Accurate chromosome segregation, monitored by the spindle assembly checkpoint (SAC), is crucial for the production of euploid cells. Previous in vitro studies by us and others showed that Mad2, a core member of the SAC, performs a checkpoint function in oocyte meiosis. Here, through an oocyte-specific knockout approach in mouse, we reconfirmed that Mad2-deficient oocytes exhibit an accelerated metaphase-to-anaphase transition caused by premature degradation of securin and cyclin B1 and subsequent activation of separase in meiosis I. However, it was surprising that the knockout mice were completely fertile and the resulting oocytes were euploid. In the absence of Mad2, other SAC proteins, including BubR1, Bub3 and Mad1, were normally recruited to the kinetochores, which likely explains the balanced chromosome separation. Further studies showed that the chromosome separation in Mad2-null oocytes was particularly sensitive to environmental changes and, when matured in vitro, showed chromosome misalignment, lagging chromosomes, and aneuploidy with premature separation of sister chromatids, which was exacerbated at a lower temperature. We reveal for the first time that Mad2 is dispensable for proper chromosome segregation but acts to mitigate environmental stress in meiotic oocytes.

A Dual Stimuli-Responsive Nanoplatform Loaded PtIV -Triptolide Prodrug for Achieving Synergistic Therapy toward Breast Cancer.

To strengthen the antitumor efficacy and avoid toxicity to normal cells of cisplatin and triptolide,herein, an acid and glutathione (GSH) dual-controlled nanoplatform for enhanced cancer treatment through the synergy of both "1+1" apoptosis and "1+1" ferroptosis is designed. Remarkably,ZIF8in response totumor microenvironmentenhances drug targeting and protects drugs from premature degradation. Meanwhile, the PtIV center can be easily reducedtocisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The releasedcisplatin and hemin in turn boost the tumor cell "1+1" apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction throughPtIV weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus "1+1"ferroptosis can be achieved. Bothinvitroandinvivoresults demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reducethe toxicity to normal cells/tissues of cisplatin and triptolide effectively. Overall, the prodrug-based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced "1+1" apoptosis and "1+1" ferroptosis therapies.

Intervention Progress of Anterior Cruciate Ligament (ACL) Reconstruction in Knee Osteoarthritis Caused by ACL Injury

In recent years, as the number of people exercising has increased, so has the number of sports injuries, including traumatic osteoarthritis caused by Anterior Cruciate Ligament ACL injury. Traumatic osteoarthritis is a disease caused by trauma to or around the joints. It is primarily distinguished by articular cartilage degradation and ossification, which can lead to pathological changes of periarticular ligaments, synovial inflammation and joint instability, mainly causing joint pain, dysfunction, including premature joint degradation and other clinical symptoms. Any age and age group can occur, generally to young adults more common. The treatment of ACL injury is generally divided into emergency care, surgical treatment, drug treatment, and non-surgical treatment. If patients have ACL injury combined with medial knee ligament injury, or combined with posterior cruciate ligament injury and lateral ligament injury, surgical repair is generally selected for treatment, or ligament reconstruction is selected for treatment. For patients with obsolete injuries, more treatment means of ligament reconstruction should be considered. The therapeutic effect of ACL reconstruction on post-traumatic osteoarthritis is still controversial. This article aims to review the relationship between ACL injury and the pathogenesis of post traumatic knee osteoarthritis, in order to provide assistance for the treatment of Osteoarthritis of the knee caused by a severe injury.

Effect of Ti fracture on mechanical properties of accumulative-roll-bonded Ti–Al composite plates

In this study, the effect of the degree of hard-phase fracture on the mechanical properties of accumulative-roll-bonded metal composite plates using experimental tests and finite element simulations. Ti–Al plates with two compositions, i.e., those with fractured and continuous intermediate Ti layers, were used as base materials and subjected to accumulative roll bonding five times. The results showed that the fracture of the intermediate Ti layer significantly degraded the mechanical properties. However, the more the Ti layer was broken down and distributed within the composite plate during accumulative roll bonding, the better were the mechanical properties. Tensile fracture of the composite plate only occurred in the Al phase, with the crack path deflected around the Ti phase. The more compact the Ti distribution, the more severe the tearing and delamination of the Al phase. Through finite element simulations, it was concluded that the shorter the distance between the Ti fragments along the loading direction, the higher the stress and the strain rate, which resulted in premature fracture and degradation of the mechanical properties.

Molecular Mechanism of Plasticizer Exudation from Polyvinyl Chloride

Plasticizers improve polymer material flexibility and durability by lowering glass transition and cold flex temperatures. While many different classes of plasticizers have been synthesized and used in various applications, several classes have been phased out due to concerns over their safety. One of the main problems that hinder the development of a new generation of efficient and safe plasticizers is the plasticizers’ migration and exudation from polymer materials, which leads to a reduction of mechanical properties and premature degradation. Here, we employed multiscale molecular dynamics, validated by experiment, to investigate the molecular mechanism of exudation of an orthophthalate plasticizer (di-2-ethylhexyl phthalate (DEHP)), non-orthophthalate plasticizers (di-n-butyl terephthalate (DnBT) and di-2-ethylhexyl terephthalate (DEHT)), and their blends from polyvinyl chloride (PVC). The results suggest that DnBT acted as an intermediary between PVC and DEHT, improving the compatibility of the plasticizer blend and reducing the degree of exudation. Specifically, it was predicted that the 70:30 wt % DnBT–DEHT blend was on par with the DEHP control system. These results also suggest that plasticizer-PVC compatibility is a stronger determinant of plasticizer exudation than the plasticizer size, diffusivity, and viscosity, given that DnBT is a smaller, more mobile, faster-diffusing, and lower-viscosity plasticizer than DEHT. Overall, our results indicate that the most important parameters that control exudation were Hansen solubility and consequently Flory–Huggins interaction parameters.

Biallelic mutations in RNA-binding protein ADAD2 cause spermiogenic failure and non-obstructive azoospermia in humans.

What are some pathogenic mutations for non-obstructive azoospermia (NOA) and their effects on spermatogenesis? Biallelic missense and frameshift mutations in ADAD2 disrupt the differentiation of round spermatids to spermatozoa causing azoospermia in humans and mice. NOA is the most severe cause of male infertility characterized by an absence of sperm in the ejaculate due to impairment of spermatogenesis. In mice, the lack of the RNA-binding protein ADAD2 leads to a complete absence of sperm in epididymides due to failure of spemiogenesis, but the spermatogenic effects of ADAD2 mutations in human NOA-associated infertility require functional verification. Six infertile male patients from three unrelated families were diagnosed with NOA at local hospitals in Pakistan based on infertility history, sex hormone levels, two semen analyses and scrotal ultrasound. Testicular biopsies were performed in two of the six patients. Adad2 mutant mice (Adad2Mut/Mut) carrying mutations similar to those found in NOA patients were generated using the CRISPR/Cas9 genome editing tool. Reproductive phenotypes of Adad2Mut/Mut mice were verified at 2 months of age. Round spermatids from the littermates of wild-type (WT) and Adad2Mut/Mut mice were randomly selected and injected into stimulated WT oocytes. This round spermatid injection (ROSI) procedure was conducted with three biological replicates and >400 ROSI-derived zygotes were evaluated. The fertility of the ROSI-derived progeny was evaluated for three months in four Adad2WT/Mut male mice and six Adad2WT/Mut female mice. A total of 120 Adad2Mut/Mut, Adad2WT/Mut, and WT mice were used in this study. The entire study was conducted over 3 years. Whole-exome sequencing was performed to detect potentially pathogenic mutations in the six NOA-affected patients. The pathogenicity of the identified ADAD2 mutations was assessed and validated in human testicular tissues and in mouse models recapitulating the mutations in the NOA patients using quantitative PCR, western blotting, hematoxylin-eosin staining, Periodic acid-Schiff staining, and immunofluorescence. Round spermatids of WT and Adad2Mut/Mut mice were collected by fluorescence-activated cell sorting and injected into stimulated WT oocytes. The development of ROSI-derived offspring was evaluated in the embryonic and postnatal stages. Three recessive mutations were identified in ADAD2 (MT1: c.G829T, p.G277C; MT2: c.G1192A, p.D398N; MT3: c.917_918del, p.Q306Rfs*43) in patients from three unrelated Pakistani families. MT1 and MT2 dramatically reduced the testicular expression of ADAD2, likely causing spermiogenesis failure in the NOA patients. Immunofluorescence analysis of the Adad2Mut/Mut male mice with the corresponding MT3 mutation showed instability and premature degradation of the ADAD2 protein, resulting in the spermiogenesis deficiency phenotype. Through ROSI, the Adad2Mut/Mut mice could produce pups with comparable embryonic development (46.7% in Adad2Mut/Mut versus 50% in WT) and birth rates (21.45 ± 10.43% in Adad2Mut/Mut versus 27.5 ± 3.536% in WT, P = 0.5044) to WT mice. The Adad2WT/Mut progeny from ROSI (17 pups in total via three ROSI replicates) did not show overt developmental defects and had normal fertility. N/A. This is a preliminary report suggesting that ROSI can be an effective treatment for infertile Adad2Mut/Mut mice. Further assisted reproductive attempts need to be carefully examined in humans during clinical trials. Our work provides functional evidence that mutations in the ADAD2 gene are deleterious and cause consistent spermiogenic defects in both humans and mice. In addition, preliminary results show that ROSI can help Adad2Mut/Mut to produce biological progeny. These findings provide valuable clues for genetic counselling on the ADAD2 mutants-associated infertility in human males. This work was supported by the National Natural Science Foundation of China (32000587, U21A20204, and 32061143006), and the National Key Research and Developmental Program of China (2019YFA0802600 and 2021YFC2700202). This work was also supported by Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China. The authors declare no competing interests.

A Versatile Brij-Linker for One-Step Preparation of Targeted Nanoparticles.

Background: Most frequently the functionalization of nanoparticles is hampered by time-consuming, sometimes harsh conjugation and purification procedures causing premature drug release and/or degradation. A strategy to circumvent multi-step protocols is to synthesize building blocks with different functionalities and to use mixtures thereof for nanoparticle preparation in one step. Methods: BrijS20 was converted into an amine derivative via a carbamate linkage. The Brij-amine readily reacts with pre-activated carboxyl-containing ligands such as folic acid. The structures of the building blocks were confirmed by different spectroscopic methods and their utility was assessed by one-step preparation and characterization of nanoparticles applying PLGA as a matrix polymer. Results: Nanoparticles were about 200 nm in diameter independent of the composition. Experiments with human folate expressing single cells and monolayer revealed that the nanoparticle building block Brij mediates a "stealth" effect and the Brij-amine-folate a "targeting" effect. As compared to plain nanoparticles, the stealth effect decreased the cell interaction by 13%, but the targeting effect increased the cell interaction by 45% in the monolayer. Moreover, the targeting ligand density and thus the cell association of the nanoparticles is easily fine-tuned by selection of the initial ratio of the building blocks. Conclusions: This strategy might be a first step towards the one-step preparation of nanoparticles with tailored functionalities. Relying on a non-ionic surfactant is a versatile approach as it might be extended to other hydrophobic matrix polymers and promising targeting ligands from the biotech pipeline.

RESISTANCE OF ADDITIONAL ROOFING UNDERLAYS OF PITCHED ROOFS AGAINST ARTIFICIAL AND NATURAL AGEING

In this paper, the author deals with the resistance of light polymer foils based on microporous functional film, used as additional waterproofing layers of pitched roofs. He exposes these foils to the effects of natural ageing and the effects of artificial ageing according to the methodology of the European test standard. Subsequently, it verifies the tensile properties of the exposed foils and compares the effects of natural and artificial ageing in order to determine the possible cause of premature degradation of these materials, which often occurs in practice. He concludes that the cause of this degradation is not excessive leniency of testing standards, but the insufficient quality of materials supplied to the European market.

Targeted delivery of temozolomide by nanocarriers based on folic acid-hollow TiO2 -nanospheres for the treatment of glioblastoma

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Its standard treatment includes a combination of surgery, radiation, and chemotherapy. The last involves the oral delivery of free drug molecules to GBM such as Temozolomide (TMZ). However, this treatment has limited effectiveness owing to the drugs premature degradation, lack of cell selectivity, and poor control of pharmacokinetics. In this work, the development of a nanocarrier based on hollow titanium dioxide (HT) nanospheres functionalized with folic acid (HT-FA) for the targeted delivery of temozolomide (HT-TMZ-FA) is reported. This approach has the potential benefits of prolonging TMZ degradation, targeting GBM cells, and increasing TMZ circulation time. The HT surface properties were studied, and the nanocarrier surface was functionalized with folic acid as a potential targeting agent against GBM. The loading capacity, protection from degradation, and drug retention time were investigated. Cell viability was performed to assess the cytotoxicity of HT against LN18, U87, U251, and M059K GBM cell lines. The cell internalization of HT configurations (HT, HT-FA, HT-TMZ-FA) was evaluated to study targeting capabilities against GBM cancer. Results show that HT nanocarriers have a high loading capacity, retain and protect TMZ for at least 48 h. Folic acid-functionalized HT nanocarriers successfully delivered and internalized TMZ to glioblastoma cancer cells with high cytotoxicity through autophagic and apoptotic cellular mechanisms. Thus, HT-FA nanocarriers could be a promising targeted delivery platform for chemotherapeutic drugs for the treatment of GBM cancer.

Toxoplasma ERK7 protects the apical complex from premature degradation.

Accurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasite Toxoplasma gondii, daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures. We previously identified the kinase ERK7 as required for maturation of the apical complex in Toxoplasma. Here, we define the Toxoplasma ERK7 interactome, including a putative E3 ligase, CSAR1. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by mislocalization from the parasite residual body to the apical complex. These data identify a protein homeostasis pathway critical for Toxoplasma replication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.

A Route to Synthesize Ionizable Lipid ALC-0315, a Key Component of the mRNA Vaccine Lipid Matrix

—The ionizable lipid ALC-0315, ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), is a component of the lipid matrix of the prophylactic SARS-CoV-2 mRNA vaccine produced by Pfizer/BioNTech. This lipid ensures efficient vaccine assembly, protects the mRNA from premature degradation, and promotes the release of the nucleic acid into the cytoplasm for its further processing after endocytosis. The present work describes a simple and economical method for the synthesis of the ALC-0315 lipid, which can be taken advantage of in mRNA vaccine production.

Increased efficacy of biologics following inhibition of autophagy in A549 lung cancer cells in bimodal treatment of doxorubicin and SAR405-loaded chitosan nanoparticles

Conventional anti-cancer drugs, including doxorubicin, are associated with high toxicity and non-specific distribution in the body which results in a cascade of side effects. Cancer cells can utilize autophagy to promote tolerance to the stress induced by anti-cancer agents; this may be the major cause of drug resistance in advanced tumors. Owing to the molecular dynamism of cancer cells, targeting the pro-apoptotic survival pathways such as autophagy may increase the effectiveness of existing therapeutic agents at lower concentrations, thereby reducing the side effects of such agents. SAR405 is an inhibitor of autophagy activity due to its molecular interactions within the ATP binding site; however, it suffers from extracellular premature degradation and poor cellular uptake. Conversely, chitosan nanoparticles are considered biologically degradable, non-toxic, and biocompatible drug delivery agents that can be used to minimize the side effects of conventional therapeutic agents whilst increasing their intracellular uptake. In this study, a binary therapeutic strategy for the enhancement of the efficacy of doxorubicin while simultaneously inhibiting autophagy via a nano-mediated delivery system is reported. Autophagic inhibition was achieved via the improvement of SAR405 cellular uptake using SAR405-loaded chitosan nanoparticles. The synthesized nanoparticles were subsequently characterized for parameters of hydrodynamic diameter and polydispersity, while encapsulation and drug loading efficiencies were determined. Morphological characterization of the nanoparticles was elucidated using electron microscopy, and the cytotoxicity of the SAR405-loaded chitosan nanoparticles in combination treatments with doxorubicin was assessed through MTT and Annexin-v apoptosis assays. Autophagy progression through autophagosome formation was also evaluated using CYTO-ID staining. Following encapsulation, the size of the SAR405-loaded chitosan nanoparticles significantly increased from 54 nm to 161 nm at 10 µM SAR405 concentration, while the polydispersity index increased from 0.11 to 0.31 denoting presence of both encapsulated and unencapsulated moieties. When A549 lung cancer cells were treated with the IC50 values of doxorubicin in combination with SAR405-encapsulated CNP, an approximately 47% more reduction in cell viability was observed via the Annexin V-FITC/PI assay compared to using doxorubicin alone. Inhibition of autophagy was also detected in cells treated with SAR405 delivered using the nanoparticle system and was thought to be the primary reason towards a decrease in the resistance of the cancer cells to doxorubicin and thus increased its efficacy at lower concentrations. Therefore, this study has demonstrated a potential way of targeting cancer cell survival pathways that can be considered an effective way of increasing the efficacy of chemotherapeutic drugs.

Dimensional Tuning of Perylene Diimide-Based Polymers for Perovskite Solar Cells with Over 24% Efficiency.

The hygroscopic dopants used in Spiro-OMeTAD hole transport material (HTM) in state-of-the-art perovskite solar cells (PSCs) inevitably induce premature degradation of the devices. Here, two multifunctional polymer interface materials based on the perylene diimides (PDI) unit are developed. It is found that quasi-two-dimensional (2D) polymer 2DP-PDI can form a denser film and exhibit better hydrophobicity than linear polymer P-PDI. Importantly, 2DP-PDI can passivate the surface defects and extract hole carriers of perovskite film more effectively, leading to much reduced nonradiative recombination loss. With polymer interface material between the perovskite and HTM layers, the optimized device using 2DP-PDI and P-PDI yields a champion PCE of 24.20% and 23.09%, respectively, along with significantly improved stability, whereas the control device shows a lower efficiency of 22.23%. These results suggest that developing multifunctional polymer interface materials can be a promising strategy to improve the efficiency and stability of PSCs.

Alkali–Silica Reactivity Potential of Reactive and Non-Reactive Aggregates under Various Exposure Conditions for Sustainable Construction

The alkali–silica reaction (ASR) is a primary cause for premature concrete degradation. An accelerated mortar bar test is often used to access the detrimental phenomena in concrete caused by the ASR of aggregates. However, this test requires a certain environmental conditioning as per ASTM C1260. The objective of this study is to explore the effects of the cement alkali content, exposure solution concentration, temperature, and test duration on mortar bar expansion. Factorial experimental design and analysis was conducted to delineate the effects of the individual factors as well as their interaction. Five different aggregates with various mineralogical properties were used, representing reactive and non-reactive aggregates. Various dosages of cement alkalis (0.40, 0.80, and 1.20 Na2Oe), sodium hydroxide (NaOH) solution concentrations (0.5, 1.0, and 1.5 N), and temperature (40 °C, 80 °C, and 100 °C) were the studied variables. Mortar bar expansion was measured at 3, 7, 14, 21, 28, 56, and 90 days. Mortar bars incorporating Jhelum aggregates incurred expansion of 0.32% at 28 days, proving to be reactive aggregates as per ASTM C1260. Similarly, specimens incorporating Taxila aggregates showed expansion of 0.10% at 28 days, indicating non-reactive nature. It was observed that specimens with Sargodha aggregates showed expansion of 0.27% at 28 days for 0.50 N NaOH solution concentration compared to 0.31% expansion for identical specimens exposed to 1.5 N solution. Moreover, expansion increased with exposure duration for all the tested specimens. Experimental results showed that the cement alkali contents had relatively lesser effect on expansion for 1.0 N NaOH; while, in the case of 0.5 N and 1.5 N NaOH, the cement alkali had a significant effect. It was noted that expansion increased with an increase in the temperature. Jhelum aggregates showed 28-day expansion of 0.290% when exposed to 40 °C, but at a temperature of 100 °C, expansion increased to 0.339%. Factorial analysis revealed that the exposure solution had a major contribution towards the expansion of mortar bar specimens. This study highlights the contribution of various exposure conditions on the ASR expansion, which leads to a decisive role in selecting the aggregate sources for various applications and exposure conditions leading to sustainable construction.