Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation

The biological mode of action of artemisinin, a potent antimalarial, has long been controversial. Previously we established a yeast model addressing its mechanism of action and found mitochondria the key in executing artemisinin's action. Here we present data showing that artemisinin directly acts on mitochondria and it inhibits malaria in a similar way as yeast. Specifically, artemisinin and its homologues exhibit correlated activities against malaria and yeast, with the peroxide bridge playing a key role for their inhibitory action in both organisms. In addition, we showed that artemisinins are distributed to malarial mitochondria and directly impair their functions when isolated mitochondria were tested. In efforts to explore how the action specificity of artemisinin is achieved, we found strikingly rapid and dramatic reactive oxygen species (ROS) production is induced with artemisinin in isolated yeast and malarial but not mammalian mitochondria, and ROS scavengers can ameliorate the effects of artemisinin. Deoxyartemisinin, which lacks an endoperoxide bridge, has no effect on membrane potential or ROS production in malarial mitochondria. OZ209, a distantly related antimalarial endoperoxide, also causes ROS production and depolarization in isolated malarial mitochondria. Finally, interference of mitochondrial electron transport chain (ETC) can alter the sensitivity of the parasite towards artemisinin. Addition of iron chelator desferrioxamine drastically reduces ETC activity as well as mitigates artemisinin-induced ROS production. Taken together, our results indicate that mitochondrion is an important direct target, if not the sole one, in the antimalarial action of artemisinins. We suggest that fundamental differences among mitochondria from different species delineate the action specificity of this class of drugs, and differing from many other drugs, the action specificity of artemisinins originates from their activation mechanism

MSSPN: Automatic First Arrival Picking using Multi-Stage Segmentation Picking Network

Picking the first arrival times of prestack gathers is called First Arrival Time (FAT) picking, which is an indispensable step in seismic data processing, and is mainly solved manually in the past. With the current increasing density of seismic data collection, the efficiency of manual picking has been unable to meet the actual needs. Therefore, automatic picking methods have been greatly developed in recent decades, especially those based on deep learning. However, few of the current supervised deep learning-based method can avoid the dependence on labeled samples. Besides, since the gather data is a set of signals which are greatly different from the natural images, it is difficult for the current method to solve the FAT picking problem in case of a low Signal to Noise Ratio (SNR). In this paper, for hard rock seismic gather data, we propose a Multi-Stage Segmentation Pickup Network (MSSPN), which solves the generalization problem across worksites and the picking problem in the case of low SNR. In MSSPN, there are four sub-models to simulate the manually picking processing, which is assumed to four stages from coarse to fine. Experiments on seven field datasets with different qualities show that our MSSPN outperforms benchmarks by a large margin.Particularly, our method can achieve more than 90\% accurate picking across worksites in the case of medium and high SNRs, and even fine-tuned model can achieve 88\% accurate picking of the dataset with low SNR

Family functioning as a moderator in the relation between perceived stress and psychotic-like experiences among adolescents during COVID-19

Background: The COVID-19 pandemic has increased psychological stress among adolescents, and the relation between perceived stress (PS) and psychotic-like experiences (PLEs) has been well-established. However, little is known about the role of family functioning (FF) in this relation, especially when adolescents experienced the extended lockdown period with family members. Methods: A total of 4807 adolescents completed this retrospective paper-and-pencil survey after school reopening between May 14th and June 6th, 2020 in Hunan Province, China. We measured PS with the Perceived stress scale (PSS-10), PLEs with the eight positive items from Community Assessment of Psychic Experiences (CAPE-8), and FF with the Family APGAR scale. We conducted subgroup analysis based on three FF levels (good, moderate, and poor) determined by previous studies. Finally, correlation and moderation analysis were performed to detect the effect of FF in the relation between PS and PLEs after adjusting for demographic variables. Results: Adolescents with poor FF had higher levels of PS and higher prevalence of PLEs compared to those with good FF (both p \u3c 0.001). FF was negatively associated with both PS (r = −0.34, p \u3c 0.001) and PLEs (r = −0.29, p \u3c 0.001). Higher FF significantly attenuated the effect of PS on PLEs after adjusting for sex and age (effect = −0.011, bootstrap 95% CI -0.018, −0.005). Conclusion: Our findings indicate that well-functioned family could protect against stress-induced PLEs among adolescents during this crisis. Thus family system could be an early interventional target for distressing psychotic-like experiences in youngsters

Overprotection and overcontrol in childhood: An evaluation on reliability and validity of 33-item expanded Childhood Trauma Questionnaire (CTQ-33), Chinese version

Overprotection and overcontrol from parents or other family members, which are not rare in the Chinese culture, have been suggested to be traumatic experiences for some children. However, research on overprotection/overcontrol is much rarer in China compared with other childhood trauma subtypes. One of the possible reasons for this is the lack of easy and feasible screening tools. In this study, we therefore translated and validated a Chinese version of the 33-item Childhood Trauma Questionnaire (CTQ-33), which was expanded from the widely-used 28-item CTQ with an additional overprotection/overcontrol subscale. A total of 248 young healthy participants were recruited and completed the Chinese version of CTQ-33, and 50 of them were retested after an interval of two weeks. At baseline, all participants also completed the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder Scale to assess their depression and anxiety, respectively. Our main findings include that: (1) the Chinese version of CTQ-33 showed a good internal consistency (Cronbach\u27s α coefficient = 0.733) and an excellent test-retest reliability over a two-week period (ICC = 0.861); (2) the previously reported significant associations between the overprotection/overcontrol and other subtypes of childhood trauma (abuse and neglect), as well as psychopathological conditions such as depression can all be replicated using the Chinese version of CTQ-33. These results suggest that the Chinese version of CTQ-33 would be a promising tool for assessing various subtypes of childhood adversities, especially the overprotection/overcontrol experiences in Chinese populations

Observations of aerosol optical properties at a coastal site in Hong Kong, South China

Temporal variations in aerosol optical properties were investigated at a coastal station in Hong Kong based on the field observation from February 2012 to February 2015. At 550 nm, the average light-scattering (151 +/- 100Mm(-1) / and absorption coefficients (8.3 +/- 6.1Mm(-1) / were lower than most of other rural sites in eastern China, while the single-scattering albedo (SSA = 0.93 +/- 0.05) was relatively higher compared with other rural sites in the Pearl River Delta (PRD) region. Correlation analysis confirmed that the darkest aerosols were smaller in particle size and showed strong scattering wavelength dependencies, indicating possible sources from fresh emissions close to the measurement site. Particles with D-p of 200-800 nm were less in number, yet contributed the most to the light-scattering coefficients among submicron particles. In summer, both Delta BC / Delta CO and SO2 / BC peaked, indicating the impact of nearby combustion sources on this site. Multi-year backward Lagrangian particle dispersion modeling (LPDM) and potential source contribution (PSC) analysis revealed that these particles were mainly from the air masses that moved southward over Shenzhen and urban Hong Kong and the polluted marine air containing ship exhausts. These fresh emission sources led to low SSA during summer months. For winter and autumn months, contrarily, Delta BC / Delta CO and SO2 / BC were relatively low, showing that the site was more under influence of well-mixed air masses from long-range transport including from South China, East China coastal regions, and aged aerosol transported over the Pacific Ocean and Taiwan, causing stronger abilities of light extinction and larger variability of aerosol optical properties. Our results showed that ship emissions in the vicinity of Hong Kong could have visible impact on the light-scattering and absorption abilities as well as SSA at Hok Tsui.Peer reviewe

Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2.

Polycomb repressive complex 2 (PRC2) is a key chromatin modifier responsible for methylation of lysine 27 in histone H3. PRC2 has been shown to interact with thousands of RNA species in vivo, but understanding the physiological function of RNA binding has been hampered by the lack of separation-of-function mutants. Here, we use comprehensive mutagenesis and hydrogen deuterium exchange mass spectrometry (HDX-MS) to identify critical residues for RNA interaction in PRC2 core complexes fro

Associations Among Suicidal Ideation, White Matter Integrity and Cognitive Deficit in First-Episode Schizophrenia

Objective: The study was aimed to investigate the possible associations among suicidal ideation, brain white matter (WM) integrity and cognitive deficit in first-episode schizophrenia (FES) using diffusion tensor imaging.Methods: The sample contained 18 FES patients with suicidal ideation (SI+), 45 FES patients without suicidal ideation (SI–) and 44 healthy controls. The Calgary Depression Scale for Schizophrenia was used to measure the suicidal ideation and depression symptoms. The whole brain WM integrity and three domains of cognitive function: working memory, verbal comprehension as well as processing speed were compared between the three groups.Results: Compared with SI–, SI+ showed preserved WM integrity as indicated by significantly higher factional anisotropy (FA) or lower mean diffusivity (MD) in multiple WM tracts, and higher FA coupled with lower MD in bilateral posterior corona radiata. Compared with SI−, SI+ were more depressed and had less cognitive deficit in working memory and verbal comprehension. The fiber tracts in bilateral posterior corona radiata connect to the precuneus as shown by probabilistic tractography, and their WM integrity disruptions were found to be positively associated with the cognitive deficits in the FES patients.Discussion: Preserved WM integrity may be a risk factor for suicidal ideation in FES patients. One possible explanation is that it contributes to preserved cognitive function, especially in working memory and verbal comprehension, which may be associated with greater insight and could lead to increased depression and suicidal ideation. The posterior corona radiata and the precuneus may be linked to the related biological processes

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements