Optimized 2-methoxyestradiol invasomes fortified with apamin: a promising approach for suppression of A549 lung cancer cells

Certain anticancer agents selectively target the nucleus of cancer cells. One such drug is 2-methoxyestradiol (2ME), which is used for treating lung cancer. To improve the therapeutic effectiveness of these agents, many new methods have been devised. 2ME was entrapped into the core of hydrophobic invasomes (INVA) covered with Phospholipon 90G and apamin (APA). The Box–Behnken statistical design was implemented to enhance the composition. Using Design-Expert software (Stat-Ease Inc., Minneapolis, MN), the INVA component quantities were optimized to obtain spherical particles with the smallest size, that is, a diameter of 167.8 nm. 2ME-INVA-APA significantly inhibited A549 cells and exhibited IC₅₀ of 1.15 ± 0.04 µg/mL, which is lower than raw 2ME (IC₅₀ 5.6 ± 0.2 µg/mL). Post 2ME-INVA-APA administration, a significant rise in cell death and necrosis was seen among the A549 cells compared to those treated with plain formula or 2ME alone. This effect was indicated by increased Bax expression and reduced Bcl-2 expression, as well as mitochondrial membrane potential loss. Moreover, the cell cycle analysis showed that 2ME-INVA-APA arrests the G2-M phase of the A549 cells. Additionally, it was observed that the micellar formulation of the drug increased the cell count in pre-G1, thereby exhibiting phenomenal apoptotic potential. Furthermore, it up-regulates caspase-9 and p53 and downregulates TNF-α and NF-κβ. Collectively, these findings showed that our optimized 2ME-INVA-APA could easily seep through the cell membrane and induce apoptosis in relatively low doses.     

Superior quality chemically reduced graphene oxide for high performance EMI shielding materials

The chemical reduction process of graphene oxide combined with a mild and controllable thermal treatment under vacuum at 200 °C for 4 hours provided a cost-effective, scalable, and high-yield route for Reduced Graphene Oxide (RGO) industrial production and became a potential candidate for producing electromagnetic interference (EMI) shielding. We investigated graphite, and RGO using l-ascorbic acid and Sodium borohydride before and after thermal treatment by carefully evaluating the chemical and morphological structures. The thermally treated l-ascorbic Acid reduction route (TCRGOL) conductivity was 2.14 × 10³ S m⁻¹ and total shielding efficiency (SET) based on mass loadings per area of shielding was 94 dB with about one-tenth less graphite weight and surpassing other graphene reduction mechanisms in the frequency range of 8.2–12.4 GHz, i.e., X-band, at room temperature while being tested using the waveguide line technique. The developed treatment represents valuable progress in the path to chemical reduction using a safe reducing agent and offering superior quality RGO rarely achieved with the top-down technique, providing a high EMI shielding performance.

The developed two-step protocol offers a superior reduced graphene oxide TCRGOL quality (7 layers), and its SET was 94 dB over the X-band.     

Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Aggressive prolactinomas responsive to temozolomide treatment: Report of two cases

Refractory aggressive prolactinomas are detected after the unresponsiveness to conventional therapies. We report two cases that underwent temozolomide treatment and have been in near‐complete remission ever since. We suggest the pathology techniques for earlier detection and, subsequently, treatment with temozolomide to reduce morbidities and better respond to therapy.     

Modeling and Control of Layer Height in Laser Wire Additive Manufacturing

Laser Wire Additive Manufacturing (LWAM) is a flexible and fast manufacturing method used to produce variants of high metal geometric complexity. In this work, a physics-based model of the bead geometry including process parameters and material properties was developed for the LWAM process of large-scale products. The developed model aimed to include critical process parameters, material properties and thermal history to describe the relationship between the layer height with different process inputs (i.e., the power, the standoff distance, the temperature, the wire-feed rate, and the travel speed). Then, a Model Predictive Controller (MPC) was designed to keep the layer height trajectory constant taking into consideration the constraints faced in the LWAM technology. Experimental validation results were performed to check the accuracy of the proposed model and the results revealed that the developed model matches the experimental data. Finally, the designed MPC controller was able to track a predefined layer height reference signal by controlling the temperature input of the system.     

Incorporation of second‐tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program

BackgroundNowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non‐invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC‐MS/MS) for the evaluation of the baby''s risk of certain metabolic disorders.MethodsThis retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second‐tier tests and secondary biomarkers to improve positive predictive value (PPV).ResultsStatistical data were recorded via call interviewing in 6–8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false‐positive rate was 0.15%.ConclusionThis study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second‐tier tests and secondary biomarkers improves PPV of neonatal screening programs.     

Forecasting the Post-Pandemic Effects of the SARS-CoV-2 Virus Using the Bullwhip Phenomenon Alongside Use of Nanosensors for Disease Containment and Cure

The COVID-19 pandemic has the tendency to affect various organizational paradigm alterations, which civilization hasyet to fully comprehend. Personal to professional, individual to corporate, and across most industries, the spectrum of transformations is vast. Economically, the globe has never been more intertwined, and it has never been subjected to such widespread disruption. While many people have felt and acknowledged the pandemic’s short-term repercussions, the resultant paradigm alterations will certainly have long-term consequences with an unknown range and severity. This review paper aims at acknowledging various approaches for the prevention, detection, and diagnosis of the SARS-CoV-2 virus using nanomaterials as a base material. A nanostructure is a material classification based on dimensionality, in proportion to the characteristic diameter and surface area. Nanoparticles, quantum dots, nanowires (NW), carbon nanotubes (CNT), thin films, and nanocomposites are some examples of various dimensions, each acting as a single unit, in terms of transport capacities. Top-down and bottom-up techniques are used to fabricate nanomaterials. The large surface-to-volume ratio of nanomaterials allows one to create extremely sensitive charge or field sensors (electrical sensors, chemical sensors, explosives detection, optical sensors, and gas sensing applications). Nanowires have potential applications in information and communication technologies, low-energy lightning, and medical sensors. Carbon nanotubes have the best environmental stability, electrical characteristics, and surface-to-volume ratio of any nanomaterial, making them ideal for bio-sensing applications. Traditional commercially available techniques have focused on clinical manifestations, as well as molecular and serological detection equipment that can identify the SARS-CoV-2 virus. Scientists are expressing a lot of interest in developing a portable and easy-to-use COVID-19 detection tool. Several unique methodologies and approaches are being investigated as feasible advanced systems capable of meeting the demands. This review article attempts to emphasize the pandemic’s aftereffects, utilising the notion of the bullwhip phenomenon’s short-term and long-term effects, and it specifies the use of nanomaterials and nanosensors for detection, prevention, diagnosis, and therapy in connection to the SARS-CoV-2.     

Impact of target point deviations on control and complication probabilities in stereotactic radiosurgery of AVMs and metastases.

OBJECTIVE: Determination of the impact of inaccuracies in the determination and setup of the target point in stereotactic radiosurgery (SRS) on the expectable complication and control probabilities. METHODS: Two randomized samples of patients with arteriovenous malformation (AVM) (n=20) and with brain metastases (n=20) treated with SRS were formed, and the probability for complete obliteration (COP) or complete remission (CRP), the size of the 10 Gy-volume in the brain tissue (VOI10), and the probability for radiation necrosis (NTCP) were calculated. The dose-effect relations for COP and CRP were fitted to clinical data. Target point deviations were simulated through random vectors and the resulting probabilities and volumes were calculated and compared with the values of the treatment plan. RESULTS: The decrease of the relative value of the control probabilities at 1mm target point deviation was up to 4% for AVMs and up to 10% for metastases. At 2 mm the median decrease was 5% for AVMs and 9% for metastases. The value for the target point deviation, at which COP and CRP decreased about 0.05 in 90% of the cases, was 1.3 mm. The increase of NTCP was maximally 0.0025 per mm target point deviation for AVMs and 0.0035/mm for metastases. The maximal increase of VOI10 was 0.7 cm(3)/mm target point deviation in both patient groups. CONCLUSIONS: The upper limit for tolerable target point deviations is at 1.3mm. If this value cannot be achieved during the system test, a supplementary safety margin should be applied for the definition of the target volume. A better accuracy level is desirable, in order to ensure optimal chances for the success of the treatment. The target point precision is less important for the minimization of the probability of radiation necroses.