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The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid β-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential.

One of the most important characteristics of ornamental plants is leaf color, which enhances the color of plant landscapes and attracts pollinators for reproduction. The leaves of Impatiens hawkeri ‘Sakimp005’ are initially green, then the middle part appears yellow, then gradually become white, while the edge remains green. In the study, leaves of I. hawkeri ‘Sakimp005’, in four developmental stages (S1-G, S2-C, S3-C, and S4-C), were selected for the determination of pigment content, chromaticity values, integrative metabolomics, and transcriptomics analyses. The carotenoid content of leaves varied significantly and regularly at four stages, and the colorimetric values corroborated the phenotypic observations. The results of integrative metabolomics and transcriptomics analysis show that the accumulation of two carotenoids (lutein and zeaxanthin), to different degrees in the leaves of I. hawkeri ‘Sakimp005’ at four stages, led to the vary yellowing phenomenon. We speculated that the carotenoid biosynthesis (containing two branches: α-branch and β-branch) in leaves by IhLUT1 and IhLUT5 in the α-branch and IhBCH2 genes in the β-branch differed. These findings provide a molecular basis for Impatiens plants’ leaf color breeding and improve the knowledge of the leaf color mechanism.

Impatiens morsei is an annual or perennial flower that is a member of the Impatiens genus in the Balsaminaceae family, with pink flowers and dark purple spots on the vexil and wing petals, which is important for the study of new flower colors of Balsaminaceae. However, there has been no study on the flavonoid biosynthesis pathway and carotenoid biosynthesis pathway of I. morsei and the mechanism of its pigment formation is still unclear. Transcriptome sequencing of spotted and non-spotted regions was performed using the petals of I. morsei at full bloom as test material. The results showed that (1) After transcriptome sequencing, 39,917 unigene sequences and 39,110 differentially expressed genes were obtained, and the number of genes that are down-expressed was higher than genes that are up-expressed. (2) Three key genes in the flavonoid biosynthetic pathway, FLS , PAL , and CHS1 , were screened out. Additionally, two key genes in the carotenoid biosynthetic pathway, ABA1 and CCS , were identified. Furthermore, two regulatory genes, MSI4 and CPC, were also selected.and analyzed the spatiotemporal expression patterns of these seven genes. The results of this study lay a theoretical foundation for the study of the formation mechanism of floral spots in I. morsei .

The continuous emergence of SARS-CoV-2 variants highlights the need of developing vaccines with broad protection. Here, according to the immune-escape capability and evolutionary convergence, the representative SARS-CoV-2 strains carrying the hotspot mutations were selected. Then, guided by structural and computational analyses, we present a mutation-integrated trimeric form of spike receptor-binding domain (mutI-tri-RBD) as a broadly protective vaccine candidate, which combined heterologous RBDs from different representative strains into a hybrid immunogen and integrated immune-escape hotspots into a single antigen. When compared with a homo-tri-RBD vaccine candidate in the stage of phase II trial, of which all three RBDs are derived from the SARS-CoV-2 prototype strain, mutI-tri-RBD induced significantly higher neutralizing antibody titers against the Delta and Beta variants, and maintained a similar immune response against the prototype strain. Pseudo-virus neutralization assay demonstrated that mutI-tri-RBD also induced broadly strong neutralizing activities against all tested 23 SARS-CoV-2 variants. The in vivo protective capability of mutI-tri-RBD was further validated in hACE2-transgenic mice challenged by the live virus, and the results showed that mutI-tri-RBD provided potent protection not only against the SARS-CoV-2 prototype strain but also against the Delta and Beta variants.

Dolichandrone spathacea(L. F.) K. Schum. is an excellent tree species for coastal protection forests. In this study, the complete chloroplast genome sequence of D. spathacea was obtained through high-throughput sequencing. The length of chloroplast genome was 159,156 bp in length, containing a large single-copy region (LSC) of 86,053 bp, a small single-copy region (SSC) of 12,635 bp, and a pair of inverted repeats (IRa and IRb) regions of 30,234 bp. The chloroplast genome with 37.95% GC content, contained 134 genes, including 90 protein-coding genes, 8 rRNA genes, and 36 tRNA genes. Phylogenetic analysis with the reported chloroplast sequences shows that D. spathacea is more closely related to Spathodea campanulata.

In this work, the tensile deformation behavior of an as-extruded AZ80 magnesium alloy under pulsed current (PC) was investigated based on microstructure observations. We found that compared with the tensile tests at room temperature (RT) and given temperature (GT), the flow stress is reduced due to both thermal and athermal effects of pulsed current. A quasi-in-situ electron backscatter diffraction (EBSD) analysis reveals that at the same strain, the geometrically necessary dislocation (GND) density of the RT sample is the highest, followed by the GT sample and the PC sample. This proves that the athermal effect can promote the annihilation of dislocations and slow down dislocation pileup, which reduces the flow stress. In addition, the twinning behavior under different deformation conditions was studied; the twins are 10−12 tension twins, which are activated with the assistance of local stress. We found that the twin fraction in the PC sample is lower than that in the RT and GT samples, due to the least accumulation of GNDs at grain boundaries, which decreases the nucleation of 10−12 tension twins.

Geopolymer materials have emerged as promising alternatives to ordinary Portland cementitious materials, offering more sustainable solutions for concrete production. Sodium aluminosilicate hydrate (N-A-S-H) serves as a crucial component in geopolymer concrete, while its thermomechanical properties at elevated temperatures remain relatively underexplored. This study examined the molecular structural variations of N-A-S-H within a temperature range of 300–900 K. The influence of different Si/Al ratios and temperature levels on molecular characteristics and atomic mobility was analyzed using the radial distribution function (RDF) and mean square displacement (MSD). The thermal conductivity of the N-A-S-H gel was determined using the Müller-Plathe reverse nonequilibrium molecular dynamics (RNEMD) method. Results show that as temperature increases, the mobility of Si and Al atoms is enhanced, and the thermal conductivity of N-A-S-H gel ranges from 1.431 to 1.857 W/m/K. The thermal conductivity increases with higher Si/Al ratios and elevated temperatures, suggesting decreased thermal insulation performance at higher Si/Al ratios and temperatures.

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the immune-escape Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments. Competing Interest Statement Q. M. Li, Y. Liang, J. Zhang, J. G. Su, Y. Q. Jin, J. W. Hou, L. F. Du, Z. B. Han, X. F. Zhang, S. Shao, H. Zhang, F. Tang, Z. M. Liu, Y. N. Hou, S. Chen, Z. H. Lei, Z. J. Ma, F. Zheng, N. Liu are listed as inventors of the pending patients for the homo-tri-RBD and mutI tri-RBD vaccines. All the other authors declared no competing interests.

Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.

A general solution for 3D Stokes flow is given which is different from, and more compact than the existing ones and more compact than them in that it involves only two scalar harmonic functions. The general solution deduced is combined with the potential theory method to study the Stokes flow induced by a rigid plate of arbitrary shape translating along the direction normal to it in an unbounded fluid. The boundary integral equation governing this problem is derived. When the plate is elliptic, exact analytical results are obtained not only for the drag force but also for the velocity distributions. These results include and complete the ones available for a circular plate. Numerical examples are provided to illustrate the main results for circular and elliptic plates. In particular, the elliptic eccentricity of a plate is shown to exhibit significant influences.