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Rookie on love : 45 voices on romance, friendship, and self-care /
Collects articles, interviews, poems, and stories on romance, friendship, and self-care from the online magazine Rookie.
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Single particle cryo-EM reconstruction of 52 kDa streptavidin at 3.2 Angstrom resolution
The fast development of single-particle cryogenic electron microscopy (cryo-EM) has made it more feasible to obtain the 3D structure of well-behaved macromolecules with a molecular weight higher than 300 kDa at ~3 Å resolution. However, it remains a challenge to obtain the high-resolution structures of molecules smaller than 200 kDa using single-particle cryo-EM. In this work, we apply the Cs-corrector-VPP-coupled cryo-EM to study the 52 kDa streptavidin (SA) protein supported on a thin layer of graphene and embedded in vitreous ice. We are able to solve both the apo-SA and biotin-bound SA structures at near-atomic resolution using single-particle cryo-EM. We demonstrate that the method has the potential to determine the structures of molecules as small as 39 kDa.
It remains a challenge to obtain high-resolution structures of molecules smaller than 200 kDa using single particle cryo-EM. Here, the authors apply the Cs-corrector-VPP coupled cryo-EM and solve structures of the 52 kDa streptavidin (SA) protein at near-atomic resolution.
Journal Article
A nanotherapeutic strategy to overcome chemotherapeutic resistance of cancer stem-like cells
Tumour heterogeneity remains a major challenge in cancer therapy owing to the different susceptibility of cells to chemotherapy within a solid tumour. Cancer stem-like cells (CSCs), which reside in hypoxic tumour regions, are characterized by high tumourigenicity and chemoresistance and are often responsible for tumour progression and recurrence. Here we report a nanotherapeutic strategy to kill CSCs in tumours using nanoparticles that are co-loaded with the differentiation-inducing agent, all-trans retinoic acid, and the chemotherapeutic drug, camptothecin. All-trans retinoic acid is released under hypoxic conditions, leading to CSC differentiation in the hypoxic niche. In differentiating CSC, the reactive oxygen species levels increase, which then causes the release of camptothecin and subsequent cell death. This dual strategy enables controlled drug release in CSCs and reduces stemness-related drug resistance, enhancing the chemotherapeutic response. In breast tumour mouse models, treatment with the nanoparticles suppresses tumour growth and prevents post-surgical tumour relapse and metastasis.Chemoresistant cancer stem-like cells (CSCs) can be selectively killed by a nanoparticle, which releases an agent under hypoxic conditions that induces CSC differentiation, and a chemotherapeutic drug in response to reactive oxygen species in differentiating CSCs.
Journal Article
Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence
Cell-mediated drug-delivery systems have received considerable attention for their enhanced therapeutic specificity and efficacy in cancer treatment. Neutrophils (NEs), the most abundant type of immune cells, are known to penetrate inflamed brain tumours. Here we show that NEs carrying liposomes that contain paclitaxel (PTX) can penetrate the brain and suppress the recurrence of glioma in mice whose tumour has been resected surgically. Inflammatory factors released after tumour resection guide the movement of the NEs into the inflamed brain. The highly concentrated inflammatory signals in the brain trigger the release of liposomal PTX from the NEs, which allows delivery of PTX into the remaining invading tumour cells. We show that this NE-mediated delivery of drugs efficiently slows the recurrent growth of tumours, with significantly improved survival rates, but does not completely inhibit the regrowth of tumours.
Neutrophils carrying drug-containing liposomes can suppress recurrence of brain tumours after surgical removal of the tumour.
Journal Article
Engineering strategies and challenges of endolysin as an antibacterial agent against Gram‐negative bacteria
Bacteriophage endolysin is a novel antibacterial agent that has attracted much attention in the prevention and control of drug‐resistant bacteria due to its unique mechanism of hydrolysing peptidoglycans. Although endolysin exhibits excellent bactericidal effects on Gram‐positive bacteria, the presence of the outer membrane of Gram‐negative bacteria makes it difficult to lyse them extracellularly, thus limiting their application field. To enhance the extracellular activity of endolysin and facilitate its crossing through the outer membrane of Gram‐negative bacteria, researchers have adopted physical, chemical, and molecular methods. This review summarizes the characterization of endolysin targeting Gram‐negative bacteria, strategies for endolysin modification, and the challenges and future of engineering endolysin against Gram‐negative bacteria in clinical applications, to promote the application of endolysin in the prevention and control of Gram‐negative bacteria. Bacteriophage endolysins have limited use against Gram‐negative bacteria for the envelop. To enhance the extracellular activity of endolysin and facilitate its crossing through the outer membrane of Gram‐negative bacteria, researchers have adopted physical, chemical, and molecular strategies for endolysin modification, to promote the application of endolysin in the prevention and control of Gram‐negative bacteria.
Journal Article
l-Aspartate: An Essential Metabolite for Plant Growth and Stress Acclimation
L-aspartate (Asp) serves as a central building block, in addition to being a constituent of proteins, for many metabolic processes in most organisms, such as biosynthesis of other amino acids, nucleotides, nicotinamide adenine dinucleotide (NAD), the tricarboxylic acid (TCA) cycle and glycolysis pathway intermediates, and hormones, which are vital for growth and defense. In animals and humans, lines of data have proved that Asp is indispensable for cell proliferation. However, in plants, despite the extensive study of the Asp family amino acid pathway, little attention has been paid to the function of Asp through the other numerous pathways. This review aims to elucidate the most important aspects of Asp in plants, from biosynthesis to catabolism and the role of Asp and its metabolic derivatives in response to changing environmental conditions. It considers the distribution of Asp in various cell compartments and the change of Asp level, and its significance in the whole plant under various stresses. Moreover, it provides evidence of the interconnection between Asp and phytohormones, which have prominent functions in plant growth, development, and defense. The updated information will help improve our understanding of the physiological role of Asp and Asp-borne metabolic fluxes, supporting the modular operation of these networks.
Journal Article
Plastome evolution of Engelhardia facilitates phylogeny of Juglandaceae
Background
Engelhardia
(Juglandaceae) is a genus of significant ecological and economic importance, prevalent in the tropics and subtropics of East Asia. Although previous efforts based on multiple molecular markers providing profound insights into species delimitation and phylogeography of
Engelhardia
, the maternal genome evolution and phylogeny of
Engelhardia
in Juglandaceae still need to be comprehensively evaluated. In this study, we sequenced plastomes from 14 samples of eight
Engelhardia
species and the outgroup
Rhoiptelea chiliantha
, and incorporated published data from 36 Juglandaceae and six outgroup species to test phylogenetic resolution. Moreover, comparative analyses of the plastomes were conducted to investigate the plastomes evolution of
Engelhardia
and the whole Juglandaceae family.
Results
The 13
Engelhardia
plastomes were highly similar in genome size, gene content, and order. They exhibited a typical quadripartite structure, with lengths from 161,069 bp to 162,336 bp. Three mutation hotspot regions (
TrnK-rps16
,
ndhF-rpl32
, and
ycf1
) could be used as effective molecular markers for further phylogenetic analyses and species identification. Insertion and deletion (InDels) may be an important driving factor for the evolution of plastomes in Juglandoideae and Engelhardioideae. A total of ten codons were identified as the optimal codons in Juglandaceae. The mutation pressure mostly contributed to shaping codon usage. Seventy-eight protein-coding genes in Juglandaceae experienced relaxed purifying selection, only
rpl22
and
psaI
genes showed positive selection (
Ka/Ks
> 1). Phylogenetic results fully supported
Engelhardia
as a monophyletic group including two sects and the division of Juglandaceae into three subfamilies. The
Engelhardia
originated in the Late Cretaceous and diversified in the Late Eocene, and Juglandaceae originated in the Early Cretaceous and differentiated in Middle Cretaceous. The phylogeny and divergence times didn’t support rapid radiation occurred in the evolution history of
Engelhardia
.
Conclusion
Our study fully supported the taxonomic treatment of at the section for
Engelhardia
species and three subfamilies for Juglandaceae and confirmed the power of phylogenetic resolution using plastome sequences. Moreover, our results also laid the foundation for further studying the course, tempo and mode of plastome evolution of
Engelhardia
and the whole Juglandaceae family.
Journal Article
Sleep, physical activity, sedentary behavior, and risk of incident dementia: a prospective cohort study of 431,924 UK Biobank participants
Although sleep, physical activity and sedentary behavior have been found to be associated with dementia risk, findings are inconsistent and their joint relationship remains unclear. This study aimed to investigate independent and joint associations of these three modifiable behaviors with dementia risks. A total of 431,924 participants (median follow-up 9.0 years) without dementia from UK Biobank were included. Multiple Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. Sleep duration, leisure-time physical activity (LTPA), and screen-based sedentary behavior individually associated with dementia risks in different non-linear patterns. Sleep duration associated with dementia in a U-shape with a nadir at 7 h/day. LTPA revealed a curvilinear relationship with dementia in diminishing tendency, while sedentary behavior revealed a J-shaped relationship. The dementia risk was 17% lower in the high LTPA group (HR[95%CI]: 0.83[0.76–0.91]) and 22% higher in the high sedentary behavior group (1.22[1.10–1.35]) compared to the corresponding low-level group, respectively. A combination of seven-hour/day sleep, moderate-to-high LTPA, and low-to-moderate sedentary behavior showed the lowest dementia risk (0.59[0.50–0.69]) compared to the referent group (longer or shorter sleep/low LTPA/high sedentary behavior). Notably, each behavior was non-linearly associated with brain structures in a pattern similar to its association with dementia, suggesting they may affect dementia risk by affecting brain structures. Our findings highlight the potential to change these three daily behaviors individually and simultaneously to reduce the risk of dementia.
Journal Article
The role of mesenchymal stem cell-derived EVs in diabetic wound healing
Diabetic foot is one of the most common complications of diabetes, requiring repeated surgical interventions and leading to amputation. In the absence of effective drugs, new treatments need to be explored. Previous studies have found that stem cell transplantation can promote the healing of chronic diabetic wounds. However, safety issues have limited the clinical application of this technique. Recently, the performance of mesenchymal stem cells after transplantation has been increasingly attributed to their production of exocrine functional derivatives such as extracellular vesicles (EVs), cytokines, and cell-conditioned media. EVs contain a variety of cellular molecules, including RNA, DNA and proteins, which facilitate the exchange of information between cells. EVs have several advantages over parental stem cells, including a high safety profile, no immune response, fewer ethical concerns, and a reduced likelihood of embolism formation and carcinogenesis. In this paper, we summarize the current knowledge of mesenchymal stem cell-derived EVs in accelerating diabetic wound healing, as well as their potential clinic applications.
Journal Article
Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease
Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APP
SWE
/PS1
ΔE9
mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis.
Journal Article