The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine–artesunate conjugates (e.g. ...ZnPcT4A), which could generate up to ca. 10‐fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation‐enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4A showed about 60‐fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.
An interesting aggregation‐enhanced sonodynamic activity (AESA) effect was first observed based on the studies of phthalocyanine–artesunate conjugates and common organic sonosensitizers, which arose from boosted ultrasonic cavitation caused by nanostructured aggregates. We believed that the AESA effect in this work could open up a new avenue for the development of efficient sonosensitizers.
Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure ...and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings’ rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.
Bioluminescence has been hypothesized as aposematic signalling, intersexual communication and a predatory strategy, but origins and relationships among bioluminescent beetles have been contentious. ...We reconstruct the phylogeny of the bioluminescent elateroid beetles (i.e. Elateridae, Lampyridae, Phengodidae and Rhagophthalmidae), analysing genomic data of Sinopyrophorus Bi & Li, and in light of our phylogenetic results, we erect Sinopyrophoridae Bi & Li, stat.n. as a clicking elaterid‐like sister group of the soft‐bodied bioluminescent elateroid beetles, that is, Lampyridae, Phengodidae and Rhagophthalmidae. We suggest a single origin of bioluminescence for these four families, designated as the ‘lampyroid clade’, and examine the origins of bioluminescence in the terminal lineages of click beetles (Elateridae). The soft‐bodied bioluminescent lineages originated from the fully sclerotized elateroids as a derived clade with clicking Sinopyrophorus and Elateridae as their serial sister groups. This relationship indicates that the bioluminescent soft‐bodied elateroids are modified click beetles. We assume that bioluminescence was not present in the most recent common ancestor of Elateridae and the lampyroid clade and it evolved among this group with some delay, at the latest in the mid‐Cretaceous period, presumably in eastern Laurasia. The delimitation and internal structure of the elaterid‐lampyroid clade provides a phylogenetic framework for further studies on the genomic variation underlying the evolution of bioluminescence.
Phylogenomic analyses define the ‘lampyroid clade’ with bioluminescent elaterid‐like Sinopyrophorus Bi & Li as a sister to soft‐bodied bioluminescent fireflies, glowworms and railroad worms (Lampyridae, Rhagophthalmidae, Phengodidae).
The ‘lampyroid clade’ is a sister to click beetles (Elateridae), but the support for the monophyletic click beetles remains low.
Fireflies and their non‐clicking relatives are modified click beetles. The first luminescent elateroid was a clicking beetle, with an estimated origin in the lower Cretaceous, putatively in Eastern Asia.
Sexual interference between male and female function in hermaphrodite plants is reduced by protandry. In environments with insufficient pollinator service, prolongation of male function owing to ...limited pollen removal could restrict the duration of female function and lower seed production. We provide evidence that this form of sexual conflict has played a role in the spread of females in gynodioecious populations of Cyananthus delavayi in the pollen-limited environments in which this subalpine species occurs. Using field experiments involving artificial pollen removal from the strongly protandrous flowers of hermaphrodites, we demonstrated a trade-off between male- and female-phase duration with no influence on overall floral longevity. Pollen removal at the beginning of anthesis resulted in hermaphrodite seed production matching that of females. In contrast, restricted pollen removal increased the duration of male function at the expense of female function lowering maternal fertility compared to females. This pattern was evident in five populations with females experiencing a twofold average seed fertility advantage compared to hermaphrodites. Gynodioecy often appears to evolve from protandrous ancestors and pollen limitation is widespread in flowering plants suggesting that sexual conflict may play an unappreciated role in the evolution of this form of sexual dimorphism.
The regulation of glycolysis and autophagy during feeding and metamorphosis in holometabolous insects is a complex process that is not yet fully understood. Insulin regulates glycolysis during the ...larval feeding stage, allowing the insects to grow and live. However, during metamorphosis, 20-hydroxyecdysone (20E) takes over and regulates programmed cell death (PCD) in larval tissues, leading to degradation and ultimately enabling the insects to transform into adults. The precise mechanism through which these seemingly contradictory processes are coordinated remains unclear and requires further research. To understand the coordination of glycolysis and autophagy during development, we focused our investigation on the role of 20E and insulin in the regulation of phosphoglycerate kinase 1 (PGK1). We examined the glycolytic substrates and products, PGK1 glycolytic activity, and the posttranslational modification of PGK1 during the development of Helicoverpa armigera from feeding to metamorphosis.
Our findings suggest that the coordination of glycolysis and autophagy during holometabolous insect development is regulated by a balance between 20E and insulin signaling pathways. Glycolysis and PGK1 expression levels were decreased during metamorphosis under the regulation of 20E. Insulin promoted glycolysis and cell proliferation via PGK1 phosphorylation, while 20E dephosphorylated PGK1 via phosphatase and tensin homolog (PTEN) to repress glycolysis. The phosphorylation of PGK1 at Y194 by insulin and its subsequent promotion of glycolysis and cell proliferation were important for tissue growth and differentiation during the feeding stage. However, during metamorphosis, the acetylation of PGK1 by 20E was key in initiating PCD. Knockdown of phosphorylated PGK1 by RNA interference (RNAi) at the feeding stage led to glycolysis suppression and small pupae. Insulin via histone deacetylase 3 (HDAC3) deacetylated PGK1, whereas 20E via acetyltransferase arrest-defective protein 1 (ARD1) induced PGK1 acetylation at K386 to stimulate PCD. Knockdown of acetylated-PGK1 by RNAi at the metamorphic stages led to PCD repression and delayed pupation.
The posttranslational modification of PGK1 determines its functions in cell proliferation and PCD. Insulin and 20E counteractively regulate PGK1 phosphorylation and acetylation to give it dual functions in cell proliferation and PCD.
Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations ...in a large Chinese general population to inform future Chinese ESCC screening guidelines.
We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models.
We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women.
This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
Objectives
To assess the risk of visceral pleural invasion (VPI) and improve the diagnosis of invasive adenocarcinoma (IA) in pure ground-glass nodules (pGGNs) in contact with pleura, through a ...comprehensive analysis of the thin-section CT features of subpleural malignant pGGNs.
Methods
CT findings and clinical information of 115 consecutive patients in our hospital between January 2012 and December 2015 who met the following criteria were retrospectively studied: (a) thin-section CT within 1 month before surgery proved pGGN in contact with pleura, and (b) the pGGN was confirmed as malignancy by surgery. Univariate analysis and a multivariate logistic regression analysis were conducted to identify the independent risk factors of IA and VPI.
Results
No pleural invasion was observed microscopically in any of the pGGNs. Univariate analysis indicated that tumour shape (
p
= 0.004), relative density (
p
= 0.038) and the existence of pleural retraction (
p
< 0.001) were significantly different between the invasive group and pre- or minimally invasive group. Multivariate logistic regression analysis revealed that pleural retraction (OR, 5.663;
p
< 0.001), lobulated tumour shape (OR, 4.812;
p
= 0.016) and tumour relative density greater than 1.60 (OR, 4.449;
p
= 0.001) were independent risk factors of IA.
Conclusions
Pulmonary adenocarcinoma manifesting as pGGN generally does not invade the pleura. A comprehensive consideration of tumour shape, relative density and tumour–pleural relationship can independently predict IA.
Key Points
• This study showed that pGGN-like adenocarcinoma generally does not invade the pleura.
• This study suggested that persistent pGGN with pleural retraction, lobulated shape and high relative density (> 1.60) may very likely be invasive adenocarcinoma.
• Using “relative density” can reduce confounding of contrast agent and respiratory status in analysis of CT images.
Efficacy of endoscopic screening for esophageal cancer is not sufficiently definitive and lacks randomized controlled trial evidence. The present study proved short‐term screening efficacy through ...describing and comparing disease stage distributions of intervention and control populations. Villages from Linzhou and Cixian were cluster randomly allocated to the intervention or to the control group and the target population of 52 729 and 43 068 individuals was 40‐69 years old, respectively, and the actual enrolled numbers were 18 316 and 21 178, respectively. TNM stage information and study‐defined stage information of esophageal cases from 2012 to 2016 were collected. Stage distributions were compared between the intervention and control groups in the total target population, as well as in the subgroup populations in terms of enrolment and before or after intervention. There were a total of 199 and 141 esophageal cancer cases in the intervention and control groups, respectively. For the target population, distributions of TNM stage were borderline significant between the two groups after intervention (P = .093). However, subgroup analysis of the enrolled population during the after‐intervention period had statistical significance for both TNM and study‐defined stage. Natural TNM stage distributions were approximately 32%, 41%, 24% and 3% for stages I to IV vs 71%, 19%, 7% and 3% in the intervention population. The natural study‐defined stage distributions from early, middle to advanced stages were approximately 18%, 49% and 33% vs 59%, 33% and 8%. Early‐stage esophageal cancer cases accounted for a higher proportion after endoscopy screening, and the efficacy in the target population depends on the intervention compliance.
Other than incidence and mortality as endpoints, in the present cluster randomized controlled study, we took distributions of disease stage (TNM stage) as the short‐term endpoint in order to evaluate the effect of esophageal cancer screening by endoscopy. The results provided real‐world data of stage distributions from the natural population. However, the change of stage distributions proved the short‐term efficacy of endoscopy screening from another perspective.
Introduction
Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin ...(Mel) has been shown to have anti‐inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD‐induced cognitive impairment and its mechanisms are unknown.
Methods
In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61–88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme‐linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription‐polymerase chain reaction and western blotting.
Results
The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)‐1creIL‐6, and tumor necrosis factor‐α and decreased the expression levels of brain‐derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein‐95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels.
Conclusions
These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.
Introduction
Currently, electroencephalogram (EEG)/electromyogram (EMG) system is widely regarded as the “golden standard” for sleep monitoring. Imperfectly, its invasive monitoring may somehow ...interfere with the natural state of sleep. Up to now, noninvasive methods for sleep monitoring have developed, which could preserve the undisturbed and naïve sleep state of mice to the greatest extent, but the feasibility of their application under different conditions should be extensive validated.
Methods
Based on existing research, we verified the feasibility of a sleep monitoring system based on mouse behaviors under different conditions. The experimental mice were exposed to various stresses and placed into a combined device comprising noninvasive sleep monitoring equipment and an EEG/EMG system, and the sleep status was recorded under different physiological, pharmacological, and pathophysiological conditions. The consistency of the parameters obtained from the different systems was calculated using the Bland–Altman statistical method.
Results
The results demonstrated that the physiological sleep times determined by noninvasive sleep monitoring system were highly consistent with those obtained from the EEG/EMG system, and the coefficients were 94.4% and 95.1% in C57BL/6J and CD‐1 mice, respectively. The noninvasive sleep monitoring system exhibited high sensitivity under the sleep‐promoting effect of diazepam and caffeine‐induced wakefulness, which was indicated by its ability to detect the effect of dosage on sleep times, and accurate determination of the sleep/wakeful status of mice under different pathophysiological conditions. After combining the data obtained from all the mice, the coefficient between the sleep times detected by behavior‐based sleep monitoring system and those obtained from the EEG/EMG equipment was determined to .94.
Conclusion
The results suggested that behavior‐based sleep monitoring system could accurately evaluate the sleep/wakeful states of mice under different conditions.
The noninvasive sleep monitoring system was synchronized with the standard electroencephalogram to record sleep time. The results of consistency test proved the feasibility of the noninvasive sleep monitoring system in recording sleep time in different states.
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