Quasi-1D titanium trisulfide (TiS3) has strong in-plane anisotropy with a direct band gap of about 1 eV, which has attracted wide attention in the fields of microelectronics and optoelectronics. ...However, the investigation of in situ synthesis, synthetic mechanism, and nonlinear optical properties of TiS3 is rarely reported. In this work, we developed a transfer-free method to grow TiS3 nanoribbons, successfully reducing the synthesis time from a few days to less than 24 h without pretreatment. Raman spectroscopy revealed TiS3 was not directly synthesized by titanium (Ti) and sulfur (S) but by the further sulfurization reaction of intermediate product TiS2. Moreover, the polarized four-wave mixing (FWM) imaging of the as-grown TiS3 samples was conducted by ultrafast nonlinear optical spectroscopy for the first time, identifying the crystal axis orientation of TiS3 accurately and quickly. Our work not only provides a rapid growth method for transfer-free synthesis of TiS3 nanoribbons on SiO2/Si substrates but also investigate the fast and non-destructive ultrafast nonlinear optical characterization of quasi-1D TiS3, which lays a foundation for understanding the synthetic mechanism and physicochemical properties of transition metal trisulfides (TMTCs) and promoting the functional device applications of TMTCs represented by TiS3.
Cohesin loss-of-function mutations are frequently observed in tumors, but the mechanism underlying its role in tumorigenesis is unclear. Here, we found that depletion of RAD21, a core subunit of ...cohesin, leads to massive genome-wide DNA breaks and 147 translocation hotspot genes, co-mutated with cohesin in multiple cancers. Increased DNA damages are independent of RAD21-loss-induced transcription alteration and loop anchor disruption. However, damage-induced chromosomal translocations coincide with the asymmetrically distributed Okazaki fragments of DNA replication, suggesting that RAD21 depletion causes replication stresses evidenced by the slower replication speed and increased stalled forks. Mechanistically, approximately 30% of the human genome exhibits an earlier replication timing after RAD21 depletion, caused by the early initiation of >900 extra dormant origins. Correspondingly, most translocation hotspot genes lie in timing-altered regions. Therefore, we conclude that cohesin dysfunction causes replication stresses induced by excessive DNA replication initiation, resulting in gross DNA damages that may promote tumorigenesis.
•Phenols and alkaloids in different Sichuan pepper species were compared.•Laiwu Sichuan pepper contained the highest content of phenols (59.60 ± 1.48 mg g−1).•Hanyuan Sichuan pepper was the richest ...in content of alkaloids (189.43 ± 2.81 mg g−1).•Linxia Sichuan pepper exhibited the strongest radical scavenging activity.•Phenols and hydroxyl-α-sanshool displayed antagonistic effect on scavenging radical.
The pericarp of Zanthoxylum bungeanum (PZB) is rich in phenols and alkaloids as a potential source of antioxidants, also known as Huajiao or Sichuan pepper in China, and is not only extensively used as a pungent culinary spice but also as a traditional medicinal plant due to its remedial properties. Previous studies have shown that PZB extract is highly effective against oxidative stress-related dysfunction in vitro and in vivo. Although phenols and alkaloids are considered as the two main antioxidant components in Zanthoxylum species, the impact of species diversity and cultivation region on the antioxidant composition and radical scavenging activity (RSA) of PZB extracts remains unknown. This study aimed to compare the phenol and alkaloid compositions in PZB extracts (S1-S7) obtained from seven cultivation regions in China. Additionally, the RSA of the PZB extracts and the contribution of individual phenols and alkaloids to RSA were evaluated. Six phenols and 14 alkaloids were identified at variable content levels in the PZB extracts using HPLC-MS2. The highest total phenolic content (59.60 ± 1.48 mg g−1) was recorded in S7 (Laiwu) while S1 (Hanyuan) was the richest in total alkaloid content (189.43 ± 2.81 mg g−1). The S5 (Linxia) exhibited the highest RSA, with 50 % scavenging concentration (IC50) values of 2.62 ± 0.05 mg L−1, 1.94 ± 0.04 mg L−1 and 158.26 ± 4.34 mg L−1, after exposure to spectrophotometric, electron paramagnetic resonance spectroscopy (EPR), and cyclic voltammetric (CV) systems. However, there was no significant correlation between the component content and RSA. Interestingly, representative phenols (rutin, quercetin, and hyperoside) and alkaloids (hydroxyl-α-sanshool (α-SOH)) displayed an antagonistic effect on the 2,2-diphenyl-1-picrylhydrazyl (DPPH·) scavenging activity, among which the impact of the quercetin-α-SOH combination was the strongest. This suggested that the interaction between phenols and alkaloids might confer important biochemical activities to PZB during processing and pharmaceutical applications.
Herein, we report the photoinitiated polymerization‐induced self‐assembly (photo‐PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one‐pot synthetic approach ...yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide‐functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo‐PISA in the large‐scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.
Polymerization‐induced self‐assembly enables the at scale synthesis of nanoparticles with a high‐density display of peptide, tunable particle size, and tunable peptide loadings. The resulting peptide brush polymer nanoparticles exhibit enhanced stability, and cell uptake efficiency and efficacy in comparison with their peptide analogues, highlighting the potential of these peptide–polymer amphiphiles as peptide delivery systems.
Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at -20 °C or -70 °C due to their poor stability, which severely restricts ...their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.
Highway constructions on the Qinghai-Tibet Plateau (QTP) face great challenges induced by the unique local environmental, geological, and engineering conditions. The large area of permafrost, great ...temperature variability, strong UV rays, and complex geological conditions are the major factors that adversely influence the long-term performance of pavement systems. Since 1960s, Chinese engineers and researchers have started conducting research on the QTP to enhance the performance and durability of pavement systems. The present paper provide a comprehensive review of challenge, research and practice of highway constructions on the QTP including the special environmental and geological conditions, history of highway constructions on the QTP, major challenges and the state-of-the-art technology of subgrade constructions on permafrost, developments of the pavement structures and materials, performance prediction and maintenance methods of pavement surfaces, and applications of the research achievements on the first expressway on the QTP (i.e., Gongyu Expressway). Based on the comprehensive literature review, it can be found that (1) frost heave and thaw weakening induced subgrade disease and longitudinal cracks on the pavement surface are complex coupled water-thermal-load problems. Engineering solutions are focusing on active cooling and thermal insulation methods, which can help to reduce temperature variations in the subgrade and thus improving its stability, (2) the harsh environmental and construction conditions may reduce the early strength and induce premature damage of cement-treated base materials. Some field validations showed that geocell-reinforced or asphalt-treated flexible base materials can provide better long-term performance, (3) the large temperature variability and strong UV rays can significantly accelerate aging of asphalt binders and greatly reduce the service life of asphalt mixtures. Various binder modification methods were developed for improving their viscoelasticity and enhance the low-temperature cracking resistance of pavement surface materials but are still lack of field validation data and comparisons of their life cycle costs. Therefore, it is recommended that a demonstration research project build test sections to examine a range of pavement structures and materials, and compare their long-term performance and life cycle costs, which can serve as important reference for future highway constructions on the QTP.
•Special environmental conditions and history of highway constructions on the Qinghai-Tibet Plateau (QTP) are introduced.•The permafrost-induced highway subgrade issues and engineering solutions are summarzied and discussed.•Status of pavement structure and base material research are presented and discussed.•Mechanisms and improvement methods of freeze-thaw and UV-aging induced of pavement surface damage are reviewed.•Design, testing and performance evaluation of the first expressway on QTP-Gongyu Expressway are presented.
Synapse pruning is essential not only for the developmental establishment of synaptic connections in the brain but also for the pathogenesis of neurodevelopmental and neurodegenerative disorders. ...However, there are no effective pharmacological means to regulate synaptic pruning during early development. Using the eye-specific segregation of the dorsal lateral geniculate nucleus (dLGN) as a model of synaptic pruning coupled with adenosine A2A receptor (A2AR) antagonism and knockout, we demonstrated while genetic deletion of the A2AR throughout the development attenuated eye-specific segregation with the attenuated microglial phagocytosis at postnatal day 5 (P5), selective treatment with the A2AR antagonist KW6002 at P2–P4 facilitated synaptic pruning of visual pathway with microglial activation, increased lysosomal activity in microglia and increased microglial engulfment of retinal ganglion cell (RGC) inputs in the dLGN at P5 (but not P10). Furthermore, KW6002-mediated facilitation of synaptic pruning was activity-dependent since tetrodotoxin (TTX) treatment abolished the KW6002 facilitation. Moreover, the A2AR antagonist also modulated postsynaptic proteins and synaptic density at early postnatal stages as revealed by the reduced immunoreactivity of postsynaptic proteins (Homer1 and metabotropic glutamate receptor 5) and colocalization of presynaptic VGlut2 and postsynaptic Homer1 puncta in the dLGN. These findings suggest that A2AR can control pruning by multiple actions involving the retinal wave, microglia engulfment, and postsynaptic stability. Thus, A2AR antagonists may represent a novel pharmacological strategy to modulate microglia-mediated synaptic pruning and treatment of neurodevelopmental disorders associated with dysfunctional pruning.
•A2AR KO tended to delay eye-specific segregation and decreased microglia phagocytosis.•The A2AR antagonist KW6002 enhanced eye-specific segregation at P5 but not P10.•KW6002 facilitated eye-specific segregation at P5 in an activity-dependent manner.•KW6002 activated the microglia and enhanced the engulfment of RGC inputs in the dLGN.•KW6002 decreased both the density of postsynaptic proteins Homer1/mGluR5 and synapse.
Introduction
To facilitate community-based dementia screening, we developed a voice recognition-based digital cognitive screener (digital cognitive screener, DCS). This proof-of-concept study aimed ...to investigate the reliability, validity as well as the feasibility of the DCS among community-dwelling older adults in China.
Methods
Eligible participants completed demographic, clinical, and the DCS. Diagnosis of mild cognitive impairment (MCI) and dementia was made based on the Montreal Cognitive Assessment (MoCA) (MCI: MoCA < 23, dementia: MoCA < 14). Time and venue for test administration were recorded and reported. Internal consistency, test-retest reliability and inter-rater reliability were examined. Receiver operating characteristic (ROC) analyses were conducted to examine the discriminate validity of the DCS in detecting MCI and dementia.
Results
A total of 103 participants completed all investigations and were included in the analysis. Administration time of the DCS was between 5.1–7.3 min. No significant difference (
p
> 0.05) in test scores or administration time was found between 2 assessment settings (polyclinic or community center). The DCS showed good internal consistency (Cronbach’s alpha = 0.73), test-retest reliability (Pearson
r
= 0.69,
p
< 0.001) and inter-rater reliability (ICC = 0.84). Area under the curves (AUCs) of the DCS were 0.95 (0.90, 0.99) and 0.77 (0.67, 086) for dementia and MCI detection, respectively. At the optimal cut-off (7/8), the DCS showed excellent sensitivity (100%) and good specificity (80%) for dementia detection.
Conclusion
The DCS is a feasible, reliable and valid digital dementia screening tool for older adults. The applicability of the DCS in a larger-scale community-based screening stratified by age and education levels warrants further investigation.
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