Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.     

Neutrophil/platelet to lymphocyte ratio in monitoring of response to TNF‐α inhibitors in psoriatic patients

Neutrophil or platelet to lymphocyte ratio (NLR and PLR) has been proposed to be used as prognostic purposes in a variety of diseases. The aim of this study was to evaluate the usefulness of these ratios in monitoring of response to TNF‐α‐inhibitors in psoriatic patients. Eighty psoriatic patients were included and treated with TNF‐α‐inhibitors for 12 months based on drug protocol. Hematologic indices, including NLR and PLR values were assessed before and after treatment. Data on psoriasis area and severity index (PASI), smoking behavior, alcohol intake habit, nail abnormality, body mass index (BMI), joint involvement, and disease duration were also recorded. PASI scores were improved significantly after one‐year treatment (P = .000). Furthermore, this type of treatment significantly reduced the NLR and PLR (P = .000). These changes were in accordance with PASI scores. Patients with BMI greater than 24.9 had higher, but non‐significant NLR and PLR than normal or lean individuals. Cigarette smokers and alcohol consumers had lower NLR and PLR values than other individuals (P < .05). There was no significant association between NLR and PLR and joint or nail involvement. Although NLR and PLR will not be helpful in primary diagnosis of inflammatory diseases, they could be accounted as monitoring tools in management of psoriasis or globally indicators of inflammation.     

Shortfalls in published neurosurgical literature

Expenditure related to neurosurgery has increased unevenly since the early 1990s. In this study we explored the literature by which clinical evidence is obtained to better direct neurosurgical practice. We searched different types of neurosurgery literature and four major neurosurgical procedures (excision of brain lesion, cerebral aneurysm clipping/coiling, discectomy, spine fusion) written in English on PubMed from 1996, the year of its launch, using the keyword "cost". Only a small and static portion of the neurosurgical literature was indexed as level I clinical evidence (randomized controlled trials), with a lack of cost appraisal in the outcome analysis of neurosurgical interventions. By way of rectification, a major increase in funding of grade I studies with cost analysis, and the requirement by peer-reviewed journals of a cost-benefit analysis, would promote the quality of clinical research yielding unquestionable advantage on national healthcare practice.     

Characterization of a potent inhibitor of platelet aggregation and release reaction isolated from allium sativum (garlic)

When added to platelet-rich plasma, aqueous extracts of garlic inhibited platelet aggregation and the release reaction. Subsequent experiments designed to characterize the inhibitory component revealed that the inhibitory activity was i) associated with small molecular-weight components, ii) the inhibitory component possessed the typical garlic odor and contained an abundance of sulfur, iii) the inhibitory activity could be extracted with organic solvents, and iv) temperatures above 56 degrees C and alkaline pH above 8.5 quickly destroyed the inhibitory activity. The Rf value of the major inhibitory component after thin-layer chromatographic separation was similar to that of allicin, an unique thiosulfinate in garlic previously shown to possess strong antibiotic and antifungal properties. Allicin was synthesized. On thin-layer chromatographic plates, allicin co-migrated with the inhibitory component in garlic. At 10 microM concentration, allicin inhibited completely platelet aggregation and the release reaction. Comparative studies suggest that the major platelet aggregation and release inhibitor in garlic may be allicin.     

Preparation of NiFe2O4@MIL-101(Fe)/GO as a novel nanocarrier and investigation of its antimicrobial properties

In this research, we have investigated a novel magnetic nanocomposite including NiFe₂O₄@MIL-101(Fe)/GO for the delivery of the antibiotic tetracycline (TC). Moreover, the antibacterial activity of NiFe₂O₄@MIL-101(Fe)/GO, NiFe₂O₄@MIL-101(Fe)/GO/TC and pure TC was evaluated by agar well diffusion and minimum inhibitory concentration (MIC) methods on both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. In addition, the cytotoxicity of NiFe₂O₄@MIL-101(Fe)/GO/TC on HeLa cells was determined by an MTT assay which showed good results. The structure of the prepared nanocarrier was investigated by various spectroscopic techniques such as Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Brunauer–Emmett–Teller (BET), and thermal gravimetric analysis (TGA). The results of this study showed that 98% of the TC was loaded on the synthesized nanocomposite. Drug release occurred at pH: 7.4 (phosphate buffer saline) and pH: 5.0 (acetate buffer) within 3 days, resulting in 77% and 85% release of the drug, respectively.

A schematic exhibition of the synthetic procedure of NiFe₂O₄@MIL-101(Fe)/GO as TC carrier and antibacterial activities.     

Controlling hydrogen release from remaining-intact Clathrate hydrates by electromagnetic fields: molecular engineering via microsecond non-equilibrium molecular dynamics

In view of the recently-predicted hydrogen release from type-II (sII) clathrate hydrates in the general 140–180 K temperature range [J. Phys. Chem. C, 125, 8430–8439 (2021)], we have investigated in the present study, by means of microsecond-long non-equilibrium molecular-dynamics simulation, the effect of externally-applied electric fields (both static and alternating) on manipulating and accelerating this H₂-escape process. In particular, we have found that judiciously-selected electromagnetic fields, in the microwave frequency range, serve to enhance dramatically this H₂-release rate – crucially, without any breakup of the hydrate lattice itself. Of those studied, we have found that 10 GHz serves as the optimal frequency to maximise hydrogen release, owing to promotion of H₂–H₂ molecular collisions inside doubly-occupied 5¹²6⁴ cages in the sII structure and optimal field-period overlap with intra-cage tetrahedral-site hopping and opportunities for inter-cage passage via hexagonal cage faces. This study opens up the vista of “field engineering” for exquisite kinetic control of large, Grid-(terawatt hour)-scale hydrogen-storage systems.

Microsecond-long non-equilibrium molecular-dynamics simulation reveals that externally-applied electric fields (both static and alternating) manipulate and accelerate the H₂-escape process from gas hydrates.     

Dendritic structured palladium complexes: magnetically retrievable,highly efficient heterogeneous nanocatalyst for Suzuki and Heck cross-coupling reactions

The recyclable nanomagnetic Pd-complex PAMAM G₀-Pd@γ-Fe₂O₃ is reported for catalytic C–C cross-coupling reactions of challenging substrates. Mainly, a great variety of aryl chlorides can be used as substrates for Suzuki–Miyaura and Mizoroki–Heck reactions under mild reaction conditions (60–90 °C) and low catalyst loading (<1 mol% Pd) in aqueous media. The presence of numerous polar groups in the polymer matrix increases the solubility of the catalyst in water, thus facilitating its operation in aqueous environments. The immobilization of the catalyst on the surface of a magnetic platform allows its effective recovery and reuse without significant loss of catalytic activity for at least six cycles with total leaching of <1% palladium metal, meeting the requirements for acceptable metal residues in the pharmaceutical industry.

The recyclable nanomagnetic Pd-complex PAMAM G₀-Pd@γ-Fe₂O₃ is reported for catalytic C–C cross-coupling reactions of challenging substrates.     

地尔硫(艹卓)与西地兰-D对心房颤动心室率的控制及其对房室传导的影响

目的:比较地尔硫革(Diltiazem)及西地兰-D对心房颤动(房颤)心室率控制的安全性和有效率以及对传导系统的影响。方法:对43例房颤患者随机地接受0.4mg西地兰-D(n-22)或0.25mg/kg地尔硫(?)(n=21)。120 min时无效者重复同剂量地尔硫(?)或0.2 mg西地兰-D。记录用药前后5、10、20、30、60 min的心室率及血压。无效者观察120 min及第2次用药者180 min的心室率及血压。19例窦性心律患者随机分为西地兰-D(n=10)和地尔硫(?)(n=9)组行希氏束电图检查测量PA、AH、HV间期而评估西地兰-D及地尔硫(?)对传导系统的影响。记录药物注射前及注射后的5、10、20、30 min的希氏束电图。结果:地尔硫(?)及西地兰-D组中180min内能有效控制心室率分别为20及15例(95.2％:68.2％,P<0.05)。地尔硫(?)及西地兰-D均延长AH间期,但对PA、HV问期无影响。结论:地尔硫(?)及西地兰-D均能减慢房颤心室率,但地尔硫(?)的有效率、心室率下降幅度优于西地兰-D。地尔硫(?)对心室率快的房颤伴充血性心力衰竭患者是一种较为合适的药物,在密切监护下应是安全的。两药均不影响HV、PA间期而通过延长AH间期减慢心室率。