Natural products in drug discovery and development: Synthesis and medicinal perspective of leonurine

Natural products, those molecules derived from nature, have been used by humans for thousands of years to treat ailments and diseases. More recently, these compounds have inspired chemists to use natural products as structural templates in the development of new drug molecules. One such compound is leonurine, a molecule isolated and characterized in the tissues of Herb leonuri. This molecule has received attention from scientists in recent years due to its potent anti-oxidant, anti-apoptotic, and anti-inflammatory properties. More recently researchers have shown leonurine to be useful in the treatment of cardiovascular and nervous system diseases. Like other natural products such as paclitaxel and artemisinin, the historical development of leonurine as a therapeutic is very interesting. Therefore, this review provided an overview of natural product discovery, through to the development of a potential new drug. Content will summarize known plant sources, the pathway used in the synthesis of leonurine, and descriptions of leonurine’s pharmacological properties in mammalian systems

Clonal Immune Responses of Mycobacterium-Specific γδ T Cells in Tuberculous and Non-Tuberculous Tissues during M. tuberculosis Infection

BACKGROUND: We previously demonstrated that unvaccinated macaques infected with large-dose M.tuberculosis(Mtb) exhibited delays for pulmonary trafficking of Ag-specific αβ and γδ T effector cells, and developed severe lung tuberculosis(TB) and "secondary" Mtb infection in remote organs such as liver and kidney. Despite delays in lungs, local immunity in remote organs may accumulate since progressive immune activation after pulmonary Mtb infection may allow IFNγ-producing γδ T cells to adequately develop and traffic to lately-infected remote organs. As initial efforts to test this hypothesis, we comparatively examined TCR repertoire/clonality, tissue trafficking and effector function of Vγ2Vδ2 T cells in lung with severe TB and in liver/kidney without apparent TB. METHODOLOGY/PRINCIPAL FINDINGS: We utilized conventional infection-immunity approaches in macaque TB model, and employed our decades-long expertise for TCR repertoire analyses. TCR repertoires in Vγ2Vδ2 T-cell subpopulation were broad during primary Mtb infection as most TCR clones found in lymphoid system, lung, kidney and liver were distinct. Polyclonally-expanded Vγ2Vδ2 T-cell clones from lymphoid tissues appeared to distribute and localize in lung TB granuloms at the endpoint after Mtb infection by aerosol. Interestingly, some TCR clones appeared to be more predominant than others in lymphocytes from liver or kidney without apparent TB lesions. TCR CDR3 spetratyping revealed such clonal dominance, and the clonal dominance of expanded Vγ2Vδ2 T cells in kidney/liver tissues was associated with undetectable or low-level TB burdens. Furthermore, Vγ2Vδ2 T cells from tissue compartments could mount effector function for producing anti-mycobacterium cytokine. CONCLUSION: We were the first to demonstrate clonal immune responses of mycobacterium-specific Vγ2Vδ2 T cells in the lymphoid system, heavily-infected lungs and lately subtly-infected kidneys or livers during primary Mtb infection. While clonally-expanded Vγ2Vδ2 T cells accumulated in lately-infected kidneys/livers without apparent TB lesions, TB burdens or lesions appeared to impact TCR repertoires and tissue trafficking patterns of activated Vγ2Vδ2 T cells

Semaphorin 3A Contributes to Secondary Blood–Brain Barrier Damage After Traumatic Brain Injury

Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To investigate the effects of SEMA3A, we used a mouse TBI model with a controlled cortical impact (CCI) device and a blood–brain barrier (BBB) injury model in vitro with oxygen-glucose deprivation (OGD). We tested post-TBI changes in SEMA3A, and its related receptors (Nrp-1 and plexin-A1) expression and distribution through western blotting and double-immunofluorescence staining, respectively. Neurological outcomes were evaluated by modified neurological severity scores (mNSSs) and beam-walking test. We examined BBB damage through Evans Blue dye extravasation, brain water content, and western blotting for VE-cadherin and p-VE-cadherin in vivo, and we examined the endothelial cell barrier through hopping probe ion conductance microscopy (HPICM), transwell leakage, and western blotting for VE-cadherin and p-VE-cadherin in vitro. Changes in miR-30b-5p were assessed by RT-PCR. Finally, the neuroprotective function of miR-30b-5p is measured by brain water content, mNSSs and beam-walking test. SEMA3A expression varied following TBI and peaked on the third day which expressed approximate fourfold increase compared with sham group, with the protein concentrated at the lesion boundary. SEMA3A contributed to neurological function deficits and secondary BBB damage in vivo. Our results demonstrated that SEMA3A level following OGD injury almost doubled than control group, and the negative effects of OGD injury can be improved by blocking SEMA3A expression. Furthermore, the expression of miR-30b-5p decreased approximate 40% at the third day and 60% at the seventh day post-CCI. OGD injury also exhibited an effect to approximately decrease 50% of miR-30b-5p expression. Additionally, the expression of SEMA3A post-TBI is regulated by miR-30b-5p, and miR-30b-5p could improve neurological outcomes post-TBI efficiently. Our results demonstrate that SEMA3A is a significant factor in secondary BBB damage after TBI and can be abolished by miR-30b-5p, which represents a potential therapeutic target

Effects of needle-plate corona plasma on improving the degradation of agricultural mulch film

Mulch film has provided significant convenience for agricultural development. However, its stable physical and chemical properties make it challenging to manage under natural conditions, potentially posing a serious environmental threat if mishandled. This study investigates the influence of various experimental factors on the degradation of agricultural film using low-temperature plasma degradation technology. A self-made needle-plate electrode structure was employed to treat polyethylene film with a high-frequency AC voltage. The study analyzesd the effects of input power, discharge time, electrode number, and air circulation on mulch film degradation. Changes in mulch quality, Raman spectrum, scanning electron microscope observations, and relative molecular mass were compared before and after treatment. The results revealed a 2.6-fold increase in mulch film degradation efficiency when the input power rised from 26 W to 80 W. While increasing input power enhanced high-energy electrons and active substances in the reaction space, energy efficiency did not proportionally increase with the degradation rate. At 51 W input power, the energy efficiency reached a maximum of 58.82 μg/(W·h). The number of needle tips influences plasma uniformity and input power, impacting film degradation efficiency. As the number of needle electrodes increases, film degradation efficiency initially decreased from 3.49% to 2.1%, then rised to 3.57%. Prolonged discharge time made the molecular chain structure more vulnerable to plasma attack and breakage. Additionally, air fluidity affects ozone concentration in the reactor, with higher concentrations in a closed environment at low input power. Increasing the input power to 80 W results in higher ozone concentration with good air fluidity, aiding in improving mulch film degradation efficiency

Recipe for ultrafast and persistent phase-change memory materials

The contradictory nature of increasing the crystallization speed while extending the amorphous stability for phase-change materials (PCMs) has long been the bottleneck in pursuing ultrafast yet persistent phase-change random-access memory. Scandium antimony telluride alloy (ScxSb2Te3) represents a feasible route to resolve this issue, as it allows a subnanosecond SET speed but years of reliable retention of the RESET state. To achieve the best device performances, the optimal composition and its underlying working mechanism need to be unraveled. Here, by tuning the doping dose of Sc, we demonstrate that Sc(0.3)Sb(2)Te(3)has the fastest crystallization speed and fairly improved data nonvolatility. The simultaneous improvement in such 'conflicting' features stems from reconciling two dynamics factors. First, promoting heterogeneous nucleation at elevated temperatures requires a higher Sc dose to stabilize more precursors, which also helps suppress atomic diffusion near ambient temperatures to ensure a rather stable amorphous phase. Second, however, enlarging the kinetic contrast through a fragile-to-strong crossover in the supercooled liquid regime should require a moderate Sc content; otherwise, the atomic mobility for crystal growth at elevated temperatures will be considerably suppressed. Our work thus reveals the recipe by tailoring the crystallization kinetics to design superior PCMs for the development of high-performance phase-change working memory technology

Theoretical Investigation of Mesh Relationship and Mesh Stiffness of Internal Spur Gears with Tooth Wear

The internal gear is part of the planetary and epicyclic gear pairs in the transmission system of the helicopter. Gear tooth wear is one of the most usual gear failures. This paper establishes an analytical model to evaluate the influence of tooth wear on the mesh relationship. A new mesh relationship can be derived for internal spur gears with tooth wear by the proposed analytical model. Consequently, using the new mesh relationship, the two most important meshing excitations, mesh stiffness and unloaded static transmission error (USTE), are quantitatively evaluated for the internal gear with tooth wear. The results indicate that tooth wear mainly affects the meshing ranges of single-tooth and double-teeth in mesh stiffness, rather than its amplitude. Additionally, the amplitudes of USTE increase with the increasing wear depth. Finally, this study can offer a foundation for the dynamic modeling and fault diagnosis of internal spur gears with wear faults