Pharmaceutical approaches for COVID-19: An update on current therapeutic opportunities

SARS-CoV-2, a newly discovered coronavirus, has been linked to the COVID-19 pandemic and is currently an important public health issue. Despite all the work done to date around the world, there is still no viable treatment for COVID-19. This study examined the most recent evidence on the efficacy and safety of several therapeutic options available including natural substances, synthetic drugs and vaccines in the treatment of COVID-19. Various natural compounds such as sarsapogenin, lycorine, biscoclaurine, vitamin B12, glycyrrhizic acid, riboflavin, resveratrol and kaempferol, various vaccines and drugs such as AZD1222, mRNA-1273, BNT162b2, Sputnik V, and remdesivir, lopinavir, favipiravir, darunavir, oseltamivir, and umifenovir, resp., have been discussed comprehensively. We attempted to provide exhaustive information regarding the various prospective therapeutic approaches available in order to assist researchers and physicians in treating COVID-19 patients

Reaction Mechanism of the Metal Precursor Pulse in Plasma-Enhanced Atomic Layer Deposition of Cobalt and the Role of Surface Facets

Cobalt is a potential candidate for replacing copper for interconnects and has been applied in the trenches and vias in the semiconductor industry. A non-oxidizing reactant is required in plasma-enhanced atomic layer deposition (PE-ALD) of thin films of metals to avoid O contamination. PE-ALD of Co has been demonstrated experimentally, but the growth mechanism and key reactions are not clear. In this paper, the reaction mechanism of metal cyclopentadienyl (Cp, C5H5) precursors (CoCp2) and NHx-terminated Co surfaces is studied by density functional theory calculations. The Cp ligands are eliminated by CpH formation via a hydrogen transfer step and desorb from the metal surface. The surface facet plays an important role in the reaction energies and activation barriers. The results show that on the NHx-terminated surfaces corresponding to ALD operating conditions (temperature range 550 K to 650 K), the two Cp ligands are eliminated completely on the Co(100) surface during the metal precursor pulse, resulting in Co atoms deposited on the Co(100) surface. However, the second Cp ligand reaction of hydrogen transfer is thermodynamically unfavorable on the Co(001) surface, resulting in CoCp fragment termination on the Co(001) surface. The final terminations after the metal precursor pulse are 3.03 CoCp/nm2 on the NHx-terminated Co(001) surface and 3.33 Co/nm2 on the NHx-terminated Co(100) surface. These final structures after the metal precursor pulse are essential to model the reaction during the following N-plasma step

The Existence of Positive Solutions for Boundary Value Problem of the Fractional Sturm-Liouville Functional Differential Equation

We study boundary value problems for the following nonlinear fractional Sturm-Liouville functional differential equations involving the Caputo fractional derivative:   CDβ(p(t)CDαu(t)) + f(t,u(t-τ),u(t+θ))=0, t∈(0,1),  CDαu(0)= CDαu(1)=( CDαu(0))=0, au(t)-bu′(t)=η(t), t∈[-τ,0], cu(t)+du′(t)=ξ(t), t∈[1,1+θ], where   CDα,  CDβ denote the Caputo fractional derivatives, f is a nonnegative continuous functional defined on C([-τ,1+θ],ℝ), 10, and η∈C([-τ,0],[0,∞)), ξ∈C([1,1+θ],[0,∞)). By means of the Guo-Krasnoselskii fixed point theorem and the fixed point index theorem, some positive solutions are obtained, respectively. As an application, an example is presented to illustrate our main results

Synergistic enhancement of cancer therapy using a combination of docetaxel and photothermal ablation induced by single-walled carbon nanotubes

Lei Wang1, Mingyue Zhang1, Nan Zhang1, Jinjin Shi1, Hongling Zhang1, Min Li1, Chao Lu2, Zhenzhong Zhang1 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2University of Maryland, College Park, MD, USA Background: Single-walled carbon nanotubes (SWNT) are poorly soluble in water, so their applications are limited. Therefore, aqueous solutions of SWNT, designed by noncovalent functionalization and without toxicity, are required for biomedical applications. Methods: In this study, we conjugated docetaxel with SWNT via p-p accumulation and used a surfactant to functionalize SWNT noncovalently. The SWNT were then conjugated with docetaxel (DTX-SWNT) and linked with NGR (Asn-Gly-Arg) peptide, which targets tumor angiogenesis, to obtain a water-soluble and tumor-targeting SWNT-NGR-DTX drug delivery system. Results: SWNT-NGR-DTX showed higher efficacy than docetaxel in suppressing tumor growth in a cultured PC3 cell line in vitro and in a murine S180 cancer model. Tumor volumes in the S180 mouse model decreased considerably under near-infrared radiation compared with the control group. Conclusion: The SWNT-NGR-DTX drug delivery system may be promising for high treatment efficacy with minimal side effects in future cancer therapy. Keywords: single-walled carbon nanotubes, docetaxel, NGR peptide, tumor-targeting, near-infrared radiatio

Raw frozen Antarctic krill (Euphausia superba) as an alternative feed source for cuttlefish Sepiella japonica in artificial breeding systems

The study aims to evaluate the feasibility of completely replacing raw frozen shrimp Palaemon gravieri diets with raw frozen Antarctic krill (Euphausia superba) in the diets of cuttlefish Sepiella japonica. To address the knowledge gap, we conducted a 60‐day feeding trial. At the end of the experiment (day 60), the cuttlefish Sepiella japonica eating Palaemon gravieri (SJP) grew significantly faster than those eating Euphausia superba (SJE), with the specific growth rate (SGR)SJP (7.92%) > (SGR)SJE (7.09%). Approximately 33.3% and 20.0% mortality was observed in the SJE and SJP, during the course of the experiment respectively. Some important fatty acids (i.e. n‐3 and n‐6 PUFAs) were elevated in SJE with respect to SJP. Replacement of Antarctic krill increased the diversity of the gut microbiome composition in the SJE group. Fluoride accumulated in the ink sac and cuttlebone of cuttlefish in SJE. Overall, these findings imply that PUFA‐rich Antarctic krill could replace P. gravieri shrimp for feeding cuttlefish S. japonica

Characterizing three-dimensional features of Antarctic subglacial lakes from the inversion of hydraulic potential—Lake Vostok as a case study

To estimate basal water storage beneath the Antarctic ice sheet, it is essential to have data on the three-dimensional characteristics of subglacial lakes. We present a method to estimate the water depth and surface area of Antarctic subglacial lakes from the inversion of hydraulic potential method. Lake Vostok is chosen as a case study because of the diverse and comprehensive measurements that have been obtained over and around the lake. The average depth of Lake Vostok is around 345±4 m. We estimated the surface area of Lake Vostok beneath the ice sheet to be about 13300±594 km2. The lake consists of two sub-basins separated by a ridge at water depths of about 200–300 m. The surface area of the northern sub-basin is estimated to be about half of that of the southern basin. The maximum depths of the northern and southern sub-basins are estimated to be about 450 and 850 m, respectively. Total water volume is estimated to be about 4658±204 km3. These estimates are compared with previous estimates obtained from seismic data and inversion of aerogravity data. In general, our estimates are closer to those obtained from the inversion of aerogravity data than those from seismic data, indicating the applicability of our method to the estimation of water depths of other subglacial lakes

The efficacy of upfront craniocerebral radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors in patients with epidermal growth factor receptor-positive non-small cell lung cancer with brain metastases

The present study aims to investigate the therapeutic value of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with cranial radiotherapy (RT) in patients with EGFR-positive non-small cell lung cancer (NSCLC) and brain metastases (BMs).MethodologyThis is a retrospective study that involved 213 patients with EGFR-NSCLC and BMs, with the patients divided into two groups: the upfront cranial RT (ucRT) group (n = 96) and the non-ucRT group (n = 117). All patients were administered with osimertinib, and those in the ucRT group also underwent RT. The overall survival (OS), progression-free survival (PFS) and intracranial PFS (IPFS) of the two groups were compared.ResultsThe ucRT group manifested a markedly higher IPFS than the non-ucRT group (29.65 months vs 21.8 months; P < 0.0001). The subgroup analysis revealed that patients with oligometastases (OLOGO-BMs; 1–3 BMs) demonstrated a notably longer OS (44.5 months vs 37.3 months; P < 0.0001), PFS (32.3 months vs 20.8 months; P = 0.6884) and IPFS (37.8 months vs 22.1 months; P < 0.0001) in the ucRT group than in the non-ucRT group. However, for patients with multiple BMs, there was no significant difference in OS (27.3 months vs 34.4 months; P = 0.0710) and PFS (13.7 months vs 13.2 months; P = 0.0516) between the ucRT group and the non-ucRT group; the ucRT group exhibited a higher IPFS (26.4 months vs 21.35 months; P = 0.0028). Cox’s multivariate analysis of patients with OLOGO-BM indicated that the use of ucRT was linked to a better OS (heart rate [HR] = 0.392; 95% confidence interval [CI]: 0.178–0.863; P = 0.020) and PFS (HR = 0.558; 95% CI: 0.316–0.986; P = 0.044).ConclusionUpfront cerebral cranial stereotactic radiosurgery can improve outcomes in EGFR-positive patients with NSCLC and OLOGO-BM. However, for patients with multiple BMs, the preferable strategy may be pre-treatment with EGFR-TKIs

Template Synthesis of Carbon Nanofibers Containing Linear Mesocage Arrays

Carbon nanofibers containing linear mesocage arrays were prepared via evaporation induced self-assembly method within AAO template with an average channel diameter of about 25 nm. The TEM results show that the mesocages have an elongated shape in the transversal direction. The results of N2 adsorption–desorption analysis indicate that the sample possesses a cage-like mesoporous structure and the average mesopore size of the sample is about 18 nm

The relationship between urinary selenium levels and risk of gestational diabetes mellitus: A nested case–control study

BackgroundSelenium (Se) is an essential trace element for the human body. Serum Se and urinary Se are also biomarkers to assess Se exposure status. However, studies focusing on the association between urinary Se and the risk of gestational diabetes mellitus (GDM) are rare.ObjectiveTo investigate the association between urinary Se and the risk of GDM.MethodsA nested case–control study based on a prospective birth cohort in Wuhan, China, which focuses on the effects of prenatal environmental factors exposure on pregnant women and children’s health was conducted. Two hundred and twenty-six cases and 452 controls were included. Maternal urine samples were collected before GDM diagnosis, and the urinary Se levels were determined. We assessed the association of urinary Se with GDM by conditional logistic regression with maternal urinary Se level as a categorical variable, and estimated the association between Se and glucose levels by multiple linear regression. The potential modifier roles of maternal age and fetal sex have also been assessed.ResultsLower urinary level of Se was significantly associated with a higher risk of GDM (OR = 2.35 for the tertile 1, 95% CI:1.36-4.06; adjusted OR = 1.79 for the tertile 2, 95%CI:1.09-2.95; p for trend = 0.01). Fetal sex had an interaction with Se in the association with GDM. The association was more pronounced among pregnant women with female fetuses than with male fetuses.DiscussionOur study suggested a significant negative association between urinary Se and the risk of GDM, and this association may vary depending on the fetal sex