A multi-functional nanoplatform for efficacy tumor theranostic applications

Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.

Attenuated niacin-induced skin flush response in individuals with clinical high risk for psychosis

Background Im paired sesitwity of he soin Mlush response bo miacin is one of the most rpicated findngs in patents with schizoprenia Howewer.prior studies have usaly focused on postonset psychusis,and ll is knowm about the dinical high-risk(CHR)phase of niacin senstity in psychosis Aims To proftle and compare the miacin flush responsge among CHR individuals(converters and non-coverters)patients with frstepso schinophrenia(FES)and healty controls(HCs).Methods Sensivily 1o ftour concentralions (0.1-0001M)of aqueous methylnicotinate was tested in 105 CHR individuals,57 patients with FES and 52 HCs.CHR individuals were further grouped as converters and non converters according to the 2-year follow-up outcomes.Skin flush response scores were rated on a 4-point scale.Results Of the 105 CHR individuals,21 individuals were lost during the study,leaving 84 CHR individuals;16(19.0%)converted to full psychosis at 2 years of fllow-up.Flush response scores identifed in the CHR samples were characterised as modest degree levels,intermediate between those of HC individuals and patients with FES.The flush responses in the CHR group mimicked the responses observed in the FES group at higher concentrations(0.01 M,0.1 M)and longer time points(15 min,20min);however,these became comparable vith the responses in the HC group at the shorter time points and at lower concentr ations.The converters exhibited lower mean flush response scores than the non-converters.Conclusions Attenuated niacin-induced flushing emerged during the early phase of psychosis.New devices should be developed and verified for objective quantification of skin responses in the CHR population.

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

Background Disrupted white matter(WM)microstructure has been commonly identified in youth at clinical high risk(CHR)for psychosis.Several lines of evidence suggest that fatty acids,especially unsaturated fatty acids(UFAs),might play a crucial role in the WM pathology of early onset psychosis.However,evidence linking UFA and WM microstructure in CHR is quite sparse.Aims We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls(HC).Methods Plasma fatty acids were assessed and diffusion tensor imaging(DTI)data were performed with tract-based spatial statistics(TBSS)analysis for 66 individuals at CHR for psychosis and 70 HC.Results Both the global and regional diffusion measures showed significant between-group differences,with decreased fractional anisotropy(FA)but increased mean diffusivity(MD)and radial diffusivity(RD)found in the CHR group compared with the HC group.On top of that,we found that in the HC group,plasma arachidic acid showed obvious trend-level associations with higher global FA,lower global MD and lower global RD,which regionally spread over the corpus callosum,right anterior and superior corona radiata,bilateral anterior and posterior limb of the internal capsule,and bilateral superior longitudinal fasciculus.However,there were no associations between global WM measures and any UFA in the CHR group.Conversely,we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.Conclusions Compared with the HC group,CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA,with a neuroprotective effect found in the HC group but not in the CHR group.Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group,highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

Altered attentive bias towards interpersonal communication information across phases of schizophrenia: an eye-tracking study

Background Eye movement abnormality in schizophrenia has been studied for several decades.However,patient differences in eye movements across phases of schizophrenia from eye-tracking studies have not been well documented.Aims This pilot study used eye-tracking technology to investigate attentive bias towards interpersonal communication information across different clinical phases of schizophrenia.Methods This study included 78 persons at clinical high risk(CHR)for schizophrenia,68 first-episode(FEZ)patients,and 39 chronically ill patients from the Shanghai At Risk for Psychosis Extending Project(SHARP Extending cohort)as well as 74 healthy controls(HCs).The experiment was an unguided-viewing task composed of 24 trials showing three types of pictures which varied in the degree of interpersonal communication.Type 1 was a scenery picture without people,type 2 was a picture with four people not communicating,and type 3 was a picture with four people communicating.We used two measures:(1)initial fixation duration and(2)total fixation duration.Results A ratio for both measures was calculated between measures for pictures with more or less interpersonal communication.The ratio of initial fixation duration for pictures with people communicating versus pictures with people not communicating was lowest in chronically ill patients(0.13(0.34))compared with HCs(0.31(0.36)),FEZ patients(0.31(0.46)),and CHR patients(0.36(0.42)).The difference in the ratios of initial fixation duration for type 2 and type 3 pictures was also significant for female participants(HCs vs chronically ill patients,t=2.706,p=0.009;CHR patients vs chronically ill patients,t=4.079,p<0.001).In addition,the ratio of initial fixation duration on pictures with people not communicating versus pictures without people negatively correlated with participants’high-risk symptoms(r=−0.35,p=0.002)among the CHR group and also correlated with the negative symptom subscore on the Positive and Negative Syndrome Scale(PANSS)among chronically ill patients(r=−0.33,p=0.037).The ratio of initial fixation duration between type 1 and type 3 pictures was associated with PANSS negative symptoms only in female patients with schizophrenia(r=−0.46,p=0.004).Conclusions These findings suggest an altered attentive bias towards pictures with a high degree of interpersonal communication information across different clinical phases in schizophrenia.The ratio of initial attentive orienting was associated with negative symptoms in female patients.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study

Background Clinical high risk(CHR)of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode.CHR exhibits cognitive deficits;however,the underlying neurobiological mechanisms remain unclear.This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin(oxy-Hb)in CHR subjects could be correlated with cognitive deficits.Methods Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome(SIPS)and the Scale of Prodromal Syndrome(SOPS)and 58 age-and sex-matched healthy participants were included in the study.All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS)Consensus Cognitive Battery(MCCB)that includes tests measuring attention,verbal memory,verbal fluency,executive function,and general intelligence.Functional near-infrared spectroscopy(fNIRS)was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices.Results We observed significantly decreased oxy-Hb levels in channel 32(located in the right superior temporal gyrus,rSTG)within the CHR individuals compared with that in the healthy controls(HCs)(t=−3.44,Bonferroni-corrected p=0.002),indicating lower brain activity.A significant positive correlation was observed between task-relatedβvalues and working memory in the CHR group(r=0.35,p=0.008).Conclusions The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis.This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

Abnormal neural oscillations in clinical high risk for psychosis:a magnetoencephalography method study

Background Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks.Abnormal neural oscillations have been discovered in patients with schizophrenia.However,there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis(CHR-P).The brain signals recorded by the magnetoencephalography(MEG)technique are not to be disrupted by the skull and scalp.Methods In this study,we applied the MEG technique to record the resting-state neural activities in CHR-P.This was followed by a detailed MEG analysis method including three steps:(1)preprocessing,which was band-pass filtering based on the 0.5-60Hz frequency range,removal of 50Hz power frequency interference,and removal of electrocardiography(ECG)and electrooculography(EOG)artefacts by independent component analysis;(2)time-frequency analysis,a multitaper time-frequency transformation based on the Hanning window,and(3)source localisation.an exact low-resolution brain electromagnetic tomography.The method was verified by comparing aparticipant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.Results Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band(4-7Hz)and the delta frequency band(1-3Hz).Also,relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.Conclusions Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups.Further work will validate these characteristics in CHR-P cohorts.

Relationships between selfreflectiveness and clinical symptoms in individuals during pre-morbid and early clinical stages of psychosis

Background Self-reflectiveness,one dimension of cognitive insight,plays a protective role in an individual’s mental state.Both high and low levels of self-reflectiveness have been reported in patients with schizophrenia and individuals at clinical high risk for the illness.Aims This study aimed to explore the relationship patterns between self-reflectiveness and clinical symptoms in individuals during the pre-morbid and early clinical stages of psychosis.Methods A total of 181 subjects,including individuals with attenuated positive symptoms(APS,n=122)and patients with first-episode psychosis(FEP,n=59),completed the Beck Cognitive Insight Scale and were evaluated using the Schedule of Assessment of Insight and Positive and Negative Syndrome Scale.All subjects were classified into three groups according to their level of selfreflectiveness:low level(LSR,n=59),medium level(MSR,n=67)and high level(HSR,n=55).Both linear and nonlinear relationships between self-reflectiveness and clinical symptoms were explored.Results More individuals with APS were classified into the MSR group,while more patients with FEP were classified into the LSR group.The LSR group demonstrated less awareness of illness than the MSR and HSR groups,more stereotyped thinking and poorer impulse control but less anxiety than the MSR group,and lower levels of blunted affect and guilt feelings than the HSR group.The MSR group demonstrated lower stereotyped thinking than the HSR group.Compared to the LSR group,the MSR group had increased selfreflectiveness,improved awareness of illness,decreased stereotyped thinking,and better impulse control,but increased feelings of guilt.The HSR group showed increased stereotyped thinking when compared to the MSR group,but the other variables did not change significantly between these two groups.Overall,self-reflectiveness demonstrated an approximately inverse S-shaped relationship with the awareness of illness,a U-shaped relationship with stereotyped thinking and poor impulse control,and an almost linear relationship with anxiety and guilt feelings.Conclusions Self-reflectiveness demonstrates complex relationships with clinical symptoms and fails to exert significant positive effects when reaching a certain high level.

Mechanical Properties and Erosive Wear Resistance of Zirconia Toughened Al_2O_3-TiC Ceramics

The effect of ZrO2, content on the fracture toughness, flexural strength and Vickers hardness as well as the erosive wear resistan properties of zirconia toughened Al2O3-TiC ceramic composites has been investigated. The results showed that the improvement in fracture toughness and flexure strength of composites with the content of zirconia less than 50% and 10% in mass fraction respectively,is primarily attributed to stress-induced transformation toughening by the analyse of X-ray diffraction. The dependance of erosion wear resistance on the attak angle and the content of ZrO2, panicles of the composites was also revealed. It is found that the erosion rate of the composites has a sharp rise at a attack angle over 65°. This phenomenon is due to a brittle response to the erosion test by microsmictural observation on eroded surface.

精神病临床高危综合征认知功能损伤的功能磁共振成像研究进展

精神病临床高危综合征以弱化的精神病性症状和认知功能损伤为特征, 随访时转化为精神分裂症的患者往往表现出更严重的认知功能损伤。近年来, 任务态功能磁共振成像研究为揭示不同认知功能损伤的神经生物学基础提供了客观特征, 为预测精神病高转化风险的人群提供了生物学标志, 并为发展早期干预提供了潜在靶点。本文对精神病临床高危综合征认知功能损伤的功能磁共振成像研究进展进行综述, 包括认知功能相关的脑区活动异常特征、与临床症状的关联等, 并对利用功能磁共振成像特征预测转化风险进行展望。

Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart

The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.

Spatial sight analysis of Hangzhou Xiaoyingzhou based on tourists’landscape preference

Tourist preferences are important for the high-quality planning and design of recreation spaces.The famous scenic locale of West Lake in Hangzhou,China,is used as an example in this study.Based on multi-source data(e.g.,online comments,and tourist photographs),we used content analysis,kernel density estimation,and image semantic segmentation technology to determine the spatial distribution of tourists’landscape preferences.We analyzed these spatial sight characteristics from the viewpoint,sight distance,and perspectives.The results show that tourists’landscape preferences are mainly concentrated on landscape architecture for recreation.The viewpoints of these preferences are concentrated in the north-south embankmentdfar beyond that of the east-west embankment.The preferences also show a spatial sequence in terms of sight distance,and the best visual effect is the open platform at the north and south islands of Xiaoyingzhou.From the perspective of vision,the degree of spatial openness in the tourists’landscape preferences is proportional to the distance of vision;the two factors have a convergent relationship.The discussion of the characteristics of tourists’landscape preference and space sight creation in Xiaoyingzhou provides a reference for the quality improvement of island recreation space.

Comprehensive profiling of EBV gene expression in nasopharyn- geal carcinoma through paired-end transcriptome sequencing

The latent expression pattern of Epstein-Barr Virus （EBV）igenes in nasopharyngeal carcinoma （NPC） has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type Ⅲ latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through real- time PCR. We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type Ⅲ latency and lyric genes. This study provided further insights into the potential role of EBV in the development of NPC.

Boosting 5-ALA-based photodynamic therapy by a liposomal nanomedicine through intracellular iron ion regulation

5-Aminolevulinic acid(5-ALA)has been approved for clinical photodynamic therapy(PDT)due to its negligible photosensitive toxicity.However,the curative effect of 5-ALA is restricted by intracellular biotransformation inactivation of 5-ALA and potential DNA repair of tumor cells.Inspired by the crucial function of iron ions in 5-ALA transformation and DNA repair,a liposomal nanomedicine(MFLs@5-ALA/DFO)with intracellular iron ion regulation property was developed for boosting the PDT of 5-ALA,which was prepared by co-encapsulating 5-ALA and DFO(deferoxamine,a special iron chelator)into the membrane fusion liposomes(MFLs).MFLs@5-ALA/DFO showed an improved pharmaceutical behavior and rapidly fused with tumor cell membrane for 5-ALA and DFO co-delivery.MFLs@5-ALA/DFO could efficiently reduce iron ion,thus blocking the biotransformation of photosensitive protoporphyrin IX(Pp IX)to heme,realizing significant accumulation of photosensitivity.Meanwhile,the activity of DNA repair enzyme was also inhibited with the reduction of iron ion,resulting in the aggravated DNA damage in tumor cells.Our findings showed MFLs@5-ALA/DFO had potential to be applied for enhanced PDT of 5-ALA.

The current status of community mental health services in three northern areas of China

Objective:This study investigated and discussed the current status of community mental health service in three northern areas of China(Beijing,Harbin,and Karamay)in an effort to improve the community mental health services in China.Methods:In this study 176 residents from communities of the three northern areas of China were involved and divided into 18 groups.The study was conducted according to a self-prepared structured interview outline.Results:The analysis was conducted based on the following four perspectives:1.commu-nity residents’understanding of the mental health problems and how they treated psychiatric patients;2.community residents’access to and application of mental health information;3.com-munity residents’attitude to accept mental health services and the factors influencing community residents to seek help from mental health services;and 4.community residents’attitude and will-ingness to participate in the activities of community mental health services.Conclusion:Based on the investigation and analysis regarding the current status of the com-munity mental health services in three northern areas of China,it is concluded that the residents do not have s clear and complete understanding of mental health.The characteristics of mental health services had a regional correlation.Currently,the mental health services do not work effectively,and the residents are somewhat passive in obtaining information about mental health.Community mental health services should be offered according to different individual needs of the residents and the actual situations of each region.

Argon mitigates post-stroke neuroinflammation by regulating M1/M2 polarization and inhibiting NF-κB/NLRP3 inflammasome signaling

Neuroinflammation plays a vital role in cerebral ischemic stroke(IS).In the acute phase of IS,microglia are activated toward the pro-inflammatory(M1)and anti-inflammatory(M2)phenotypes.Argon,an inert gas,can reduce neuroinflammation and alleviate ischemia/reperfusion(I/R)injury.However,whether argon regulates M1/M2 polarization to protect against I/R injury as well as the underlying mechanism has not been reported.In this study,we analyzed the activation and polarization of microglia after I/R injury with or without argon administration and explored the effects of argon on NLRP3 inflammasome-mediated inflammation in microglia in vitro and in vivo.The results showed that argon application inhibited the activation of M1 microglia/macrophage in the ischemic penumbra and the expression of proteins related to NLRP3 inflammasome and pyroptosis in microglia.Argon administration also inhibited the expression and processing of IL-1β,a primary pro-inflammatory cytokine.Thus,argon alleviates I/R injury by inhibiting pro-inflammatory reactions via suppressing microglial polarization toward M1 phenotype and inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.More importantly,we showed that argon worked better than the specific NLRP3 inflammasome inhibitor MCC950 in suppressing neuroinflammation and protecting against cerebral I/R injury,suggesting the therapeutic potential of argon in neuroinflammation-related neurodegeneration diseases as a potent gas inhibitor of the NLRP3 inflammasome signaling pathway.

Preparation and pharmacokinetics in vivo of linarin solid dispersion and liposome

Objective:The current investigation aimed to determine the appropriate dosage form by comparing solid dispersion and liposome to achieve the purpose of improving the solubility and bioavailability of linarin.Methods:Linarin solid dispersion(LSD)and linarin liposome(LL)were developed via the solvent method and the thin film hydration method respectively.The Transwell chamber model of Caco-2 cells was established to evaluate the absorption of drug.The pharmacokinetics of linarin,LSD and LL in rats after ig administration were carried out by high performance liquid chromatography(HPLC)method.Results:The solubility of LSD and LL was severally 3.29 times and 3.09 times than that of linarin.The permeation coefficients of LSD and LL were greater than 10^(-6),indicating that the absorption of LSD and LL were both better than linarin.The bioavailability of the LSD was 3.363 times higher than that of linarin,and the bioavailability of LL was 0.9886 times higher than that of linarin.Conclusion:The linarin was more suitable for making solid dispersion to enhance its solubility and bioavailability.