[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098-3.97 µM (0.066-2.68 µg mL-1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Childhood Neglect and Psychological Distress Among Pregnant Women: The Chain Multiple Mediation Effect of Perceived Social Support and Positive Coping.

This study aimed to investigate the association between childhood neglect and psychological distress in pregnant women and to assess whether perceived social support and coping styles mediated this association. Pregnant women (N = 276) recruited from the prenatal clinic of a comprehensive hospital in China participated in this study. Participants reported their experiences of childhood neglect and abuse, depression, anxiety, perceived social support, and coping styles. Childhood neglect was positively associated with psychological distress. Perceived social support mediated the relationship between childhood neglect and psychological distress. Perceived social support and positive coping acted as chain mediators between childhood neglect and psychological distress. Childhood neglect is a risk factor for psychological distress during pregnancy independent of childhood abuse; perceived social support and positive coping can influence this relationship.

Genetic boundaries delineate the potential human pathogen Salmonella bongori into discrete lineages: divergence and speciation.

BACKGROUND: Salmonella bongori infect mainly cold-blooded hosts, but infections by S. bongori in warm-blooded hosts have been reported. We hypothesized that S. bongori might have diverged into distinct phylogenetic lineages, with some being able to infect warm-blooded hosts. RESULTS: To inspect the divergence status of S. bongori, we first completely sequenced the parakeet isolate RKS3044 and compared it with other sequenced S. bongori strains. We found that RKS3044 contained a novel T6SS encoded in a pathogenicity island-like structure, in addition to a T6SS encoded in SPI-22, which is common to all S. bongori strains so far reported. This novel T6SS resembled the SPI-19 T6SS of the warm-blooded host infecting Salmonella Subgroup I lineages. Genomic sequence comparisons revealed different genomic sequence amelioration events among the S. bongori strains, including a unique CTAG tetranucleotide degeneration pattern in RKS3044, suggesting non-overlapping gene pools between RKS3044 and other S. bongori lineages/strains leading to their independent accumulation of genomic variations. We further proved the existence of a clear-cut genetic boundary between RKS3044 and the other S. bongori lineages/strains analyzed in this study. CONCLUSIONS: The warm-blooded host-infecting S. bongori strain RKS3044 has diverged with distinct genomic features from other S. bongori strains, including a novel T6SS encoded in a previously not reported pathogenicity island-like structure and a unique genomic sequence degeneration pattern. These findings alert cautions about the emergence of new pathogens originating from non-pathogenic ancestors by acquiring specific pathogenic traits.

Effectiveness of two guided self-administered interventions for psychological distress among women with infertility: a three-armed, randomized controlled trial.

STUDY QUESTION: What is the effect of two guided self-administered interventions on psychological distress in women undergoing IVF or ICSI? SUMMARY ANSWER: A brief mindfulness intervention significantly reduced depression and improved sleep quality, while the gratitude journal intervention showed no significant effect on any outcome variables. WHAT IS KNOWN ALREADY: Mindfulness and gratitude journal interventions have been found to be beneficial in reducing negative affect and improving well-being. However, there are very few mental health professionals who implement such interventions in low- and middle-income countries. Therefore, two guided self-administered interventions for women with infertility were designed to help them cope with their psychological distress. STUDY DESIGN, SIZE, DURATION: A three-armed, randomized controlled trial was designed to evaluate the mindfulness and gratitude journal interventions for women undergoing IVF/ICSI. Between May 2016 and November 2017, at the reproductive center in a public hospital, 234 women were randomly assigned to the brief mindfulness group (BMG, n = 78), gratitude journal group (GJG, n = 78) or control group (CG, n = 78). The inclusion criteria were being a woman undergoing her first cycle of IVF, having at least junior middle school education and having no biological or adopted children. PARTICIPANTS/MATERIALS, SETTING, METHODS: Female infertility patients (n = 346) were approached, and 112 did not meet the inclusion criteria. All three randomized groups completed questionnaires on the day of down-regulation (T1), the day before embryo(s) transfer (T2), and 3 days before the pregnancy test (T3). The BMG completed four sessions and listened to a 20-minute audio daily, including guided mindfulness breathing and body scan. The GJG completed four sessions and wrote three gratitude journals daily. The CG received routine care. A generalized estimating equation was used in an intention-to-treat analysis. The primary outcome was depression. Secondary outcomes were anxiety, sleep quality, infertility-related stress, mindfulness and gratitude. MAIN RESULTS AND THE ROLE OF CHANCE: Participants of the BMG showed decreased depression (mean difference (MD) = -1.69, [-3.01, -0.37], d = 0.44) and improved sleep quality (MD = -1.24, [-1.95, -0.39], d = 0.43) compared to the CG, but the effect was not significant for anxiety, Fertility Problem Inventory totals, mindfulness, gratitude scores or pregnancy rates. The BMG showed a significant reduction in depression and improvement in sleep quality between T1 and T2, a continuous significant reduction between T1 and T3 and no reduction between T2 and T3. There were no significant effects on any of the variables for the GJG. LIMITATIONS, REASONS FOR CAUTION: The inclusion criteria may result in bias because some participants with low education were excluded and only women with infertility were included. A low compliance rate occurred in the gratitude journals group. Moreover, men were not included in this study. Further research should consider including spouses of the target population. WIDER IMPLICATIONS OF THE FINDINGS: The brief mindfulness intervention was beneficial in decreasing depression and improving sleep quality. Implementation of guided self-administered mindfulness could make the psychological counseling service more accessible for patients with infertility in resource-poor settings. The efficiency and feasibility of the gratitude journal intervention needs to be investigated further. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Social Science Foundation (17BSH054). The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16008452. TRIAL REGISTRATION DATE: 9 May 2016. DATE OF FIRST PATIENT'S ENROLMENT: 15 May 2016.

Gender differences in factors associated with depression in infertility patients.

AIMS: To clarify gender differences in the demographic variables and infertility problems associated with depression among men and women undergoing infertility treatment. DESIGN: A cross-sectional study. METHODS: We surveyed 380 women and 360 men undergoing infertility treatment at the reproductive medicine center of a hospital in China's Ningxia Province from March - September 2016. RESULTS: For women, ethnicity, the number of clinic visits, social concern, and sexual concern were factors linked with depression symptoms. For men, treatment cost pressure and social concern were significantly associated with depression symptoms. CONCLUSION: Psychological counseling and intervention programs should be integrated into in-vitro fertilization treatments and interventions should be targeted based on gender differences. IMPACT: The provision of treatment-related sexual knowledge by nurses is indispensable for infertile participants. Mental health policies should be developed to facilitate the implementation of psychological services. Psychological counseling and intervention programs should be integrated into in vitro fertilization treatment to help men and women with infertility cope with psychological distress.

Profiles and characteristics of clinical subtypes of perinatal depressive symptoms: A latent class analysis.

AIMS: To investigate clinically relevant subtypes of perinatal depressive symptoms. DESIGN: Cross-sectional study. METHODS: A sample of 2,783 women at different prenatal and postnatal periods was recruited between August 2015 - August 2017. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data analyses consisted of latent class analysis (LCA), analysis of variance and multinomial logistic regression. RESULTS: (a) Five latent subtypes (Classes 5/4/3/1/2) were identified: 'no symptoms', 'mild physio-somatic symptoms', 'severe physio-somatic symptoms and moderate anhedonia', 'moderate-to-severe symptoms' and 'severe symptoms'; (b) Postpartum women were more likely to belong to the severe depressive symptoms group, whereas pregnant women were likely to report severe physio-somatic symptoms; and (c) History of abortion and perinatal complications increased the likelihood of belonging to all moderate-to-severe classes. Lower levels of education increased the probability of belonging to Class 2. Younger women were more likely to be categorized into Classes 1 and 2. CONCLUSIONS: This is the first study to examine heterogeneity of perinatal depressive symptoms and delineate the characteristics of subtypes at different prenatal and postnatal periods via the PHQ-9, using LCA in a Chinese general population. IMPACT: This research details the heterogeneity of perinatal depressive symptoms and delineates the characteristics of subtypes at different prenatal and postnatal periods in a Chinese general population.

Effectiveness of self-help psychological interventions for treating and preventing postpartum depression: a meta-analysis.

Previous studies have reported different effect sizes for self-help interventions designed to reduce postpartum depression symptoms; therefore, a comprehensive quantitative review of the research was required. A meta-analysis was conducted to examine the effectiveness of self-help interventions designed to treat and prevent postpartum depression, and identified nine relevant randomized controlled trials. Differences in depressive symptoms between self-help interventions and control conditions, changes in depressive symptoms following self-help interventions, and differences in postintervention recovery and improvement rates between self-help interventions and control conditions were assessed in separate analyses. In treatment trials, depression scores continued to decrease from baseline to posttreatment and follow-up assessment in treatment subgroups. Changes in treatment subgroups' depression scores from baseline to postintervention assessment were greater relative to those observed in prevention subgroups. Self-help interventions produced larger overall effects on postpartum depression, relative to those observed in control conditions, in posttreatment (Hedges' g = 0.51) and follow-up (Hedges' g = 0.32) assessments; and self-help interventions were significantly more effective, relative to control conditions, in promoting recovery from postpartum depression. Effectiveness in preventing depression did not differ significantly between self-help interventions and control conditions.The findings suggested that self-help interventions designed to treat postpartum depression reduced levels of depressive symptoms effectively and decreased the risk of postpartum depression.

A non-linear relationship between the cumulative exposure to occupational stressors and nurses' burnout and the potentially emotion regulation factors.

BACKGROUND: Stressful situations can increase the likelihood of nurses experiencing negative emotions, especially burnout. AIMS: To explore the association of cumulative exposure to occupational stressors and emotion regulation strategies with nurses' burnout. METHODS: Participants were 602 nurses from three general hospitals in Jinan, China. Social demographic characteristics, occupational stress, burnout, and emotion regulation strategies (cognitive reappraisal, expressive suppression, and rumination), were assessed. RESULTS: Nearly 70% of nurses reported that they were burnt out. Those with a moderate level and high level of stressors were 3.203 times and 26.444 times more likely to have burnout, respectively (x2trend = 62.732). Logistic regression revealed that nurses had higher cognitive reappraisal score (odds ratios (OR) = 0.941), scored lower for burnout. Those who had higher expressive suppression score (OR = 1.054), higher rumination score (OR = 1.037), and a higher level of stressors (OR = 2.779-18.259) scored higher for burnout. The results of sensitivity analysis were similar. CONCLUSIONS: A non-linear relationship exists between the cumulative exposure to occupational stressors and nurses' burnout. Those who less frequently use cognitive reappraisal, more frequently use rumination and expressive suppression, and have a high level of stressors may be more likely to experience burnout.

Disrupted Executive Function and Aggression in Individuals With a History of Adverse Childhood Experiences: An Event-Related Potential Study.

Here, we explored the functional and neural mechanisms underlying aggression related to adverse childhood experiences. We assessed behavioral performance and event-related potentials during a go/no-go and N-back paradigm. The participants were 15 individuals with adverse childhood experiences and high aggression (ACE + HA), 13 individuals with high aggression (HA), and 14 individuals with low aggression and no adverse childhood experiences (control group). The P2 latency (initial perceptual processing) was longer in the ACE + HA group for the go trials. The HA group had a larger N2 (response inhibition) than controls for the no-go trials. Error-related negativity (error processing) in the ACE + HA and HA groups was smaller than that of controls for false alarm go trials. Lastly, the ACE + HA group had shorter error-related negativity latencies than controls for false alarm trials. Overall, our results reveal the neural correlates of executive function in aggressive individuals with ACEs.

Breast-related stereotype threat contributes to a symptom cluster in women with breast cancer.

AIMS AND OBJECTIVES: To investigate the prevalence of breast-related stereotype threat and its effects on a symptom cluster consisting of anxiety, depression and fatigue and on each symptom. BACKGROUND: The stereotype that breasts are a sign of women's femininity results in patients with breast cancer fearing diminished femininity and rejection, which may induce psychological problems that co-occur as a symptom cluster. DESIGN: Cross-sectional study. METHODS: A total of 131 patients with breast cancer postmastectomy completed the study. A question measuring breast-related stereotype threat, the Hospital Anxiety and Depression Scale and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale were used to assess their breast-related stereotype threat and symptoms of anxiety, depression and fatigue. RESULTS: Of the 131 patients who answered the breast-related stereotype threat question, 86 (65·6%) reported breast-related stereotype threat. They did not differ significantly in social and clinical characteristics compared with those without the stereotype, but did report significantly higher levels of the symptom cluster and each symptom (anxiety, depression and fatigue). The odds ratios of the stereotype were significant for the symptom cluster, depression and fatigue (odds ratios = 2·52-3·98, p < 0·05). CONCLUSION: The breast-related stereotype threat was common in patients with breast cancer. There was about a twofold increase in their risk of experiencing the symptom cluster and symptoms of depression and fatigue. RELEVANCE TO CLINICAL PRACTICE: In clinical practice, breast-related stereotype threat should be measured together with prevalent symptoms (e.g. anxiety, depression and fatigue) in patients with breast cancer. Our findings will aid the development of interventions for improving the mental health of women with breast cancer.

Predictors of occupational burnout among nurses: a dominance analysis of job stressors.

AIMS AND OBJECTIVES: To quantitatively compare dimensions of job stressors' effects on nurses' burnout. BACKGROUND: Nurses, a key group of health service providers, often experience stressors at work. Extensive research has examined the relationship between job stressors and burnout; however, less has specifically compared the effects of job stressor domains on nurses' burnout. DESIGN: A quantitative cross-sectional survey examined three general hospitals in Jinan, China. METHOD: Participants were 602 nurses. We compared five potential stressors' ability to predict nurses' burnout using dominance analysis and assuming that each stressor was intercorrelated. RESULTS: Strong positive correlations were found between all five job stressors and burnout. Interpersonal relationships and management issues most strongly predicted participants' burnout (11·3% of average variance). CONCLUSION: Job stressors, and particularly interpersonal relationships and management issues, significantly predict nurses' job burnout. RELEVANCE TO CLINICAL PRACTICE: Understanding the relative effect of job stressors may help identify fruitful areas for intervention and improve nurse recruitment and retention.

Test of the stress sensitization model in adolescents following the pipeline explosion.

PURPOSE: The stress sensitization model states that early traumatic experiences increase vulnerability to the adverse effects of subsequent stressful life events. This study examined the effect of stress sensitization on development of posttraumatic stress disorder (PTSD) symptoms in Chinese adolescents who experienced the pipeline explosion. METHODS: A total of 670 participants completed self-administered questionnaires on demographic characteristics and degree of explosion exposure, the Childhood Trauma Questionnaire (CTQ), and the Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C). Associations among the variables were explored using MANOVA, and main effects and interactions were analyzed. RESULTS: Overall MANOVA tests with the PCL-C indicated significant differences for gender (F=6.86, p=.000), emotional abuse (F=6.79, p=.000), and explosion exposure (F=22.40, p=.000). There were significant interactions between emotional abuse and explosion exposure (F=3.98, p=.008) and gender and explosion exposure (F=2.93, p=.033). CONCLUSIONS: Being female, childhood emotional abuse, and a high explosion exposure were associated with high PTSD symptom levels. Childhood emotional abuse moderated the effect of explosion exposure on PTSD symptoms. Thus, stress sensitization influenced the development of PTSD symptoms in Chinese adolescents who experienced the pipeline explosion as predicted by the model.

Post-traumatic stress disorder symptoms in first-time myocardial infarction patients: roles of attachment and alexithymia.

AIMS: To explore the roles of attachment and alexithymia in the severity of post-traumatic stress disorder symptoms and to specify the relationship between sub-dimensions of attachment, alexithymia and posttraumatic stress disorder symptoms in patients with first-time myocardial infarction in mainland China. BACKGROUND: Patients experiencing myocardial infarction have a risk of developing post-traumatic stress disorder symptoms. However, there have been few studies on the roles of attachment and alexithymia. DESIGN: A cross-sectional survey design. METHODS: Ninety-seven patients participated in the assessment of post-traumatic stress disorder symptoms, attachment and alexithymia from June-December in 2012. To assess post-traumatic stress disorder symptoms and their correlates, we administered the Post-traumatic Stress Disorder Checklist-Civilian Version, the 20-item Toronto Alexithymia Scale and the Experiences in Close Relationships Scale 5-17 days after the remission of first myocardial infarction attack. RESULTS: Twenty-five (25·77%) patients met the criteria of posttraumatic stress disorder symptoms. Greater attachment anxiety and avoidance were associated with more severe posttraumatic stress disorder symptoms. Except for externally oriented thinking, all dimensions of alexithymia were significantly correlated with post-traumatic stress symptoms. In the regression model, attachment anxiety and difficulties identifying feelings were found to be predictive and the total regression equation explained 24·2% variance of posttraumatic stress disorder symptoms among myocardial infarction patients. CONCLUSION: First-time myocardial infarction patients were at risk of developing posttraumatic stress disorder symptoms. Attachment anxiety and difficulties identifying feelings were positively associated with posttraumatic stress disorder symptoms in the early stage of myocardial infarction rehabilitation. It is essential to evaluate the causal relationship between attachment, alexithymia and posttraumatic stress disorder symptoms in longitudinal studies.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Genomic comparison of Salmonella typhimurium DT104 with non-DT104 strains.

DT104 emerged as a new branch of Salmonella typhimurium with resistance to multiple antimicrobials. To reveal some general genomic features of DT104 for clues of evolutionary events possibly associated with the emergence of this relatively new type of this pathogen, we mapped 11 independent DT104 strains and compared them with non-DT104 S. typhimurium strains. We found that all 11 DT104 strains contained three insertions absent in non-DT104 strains, i.e., the previously reported ST104, ST104B and ST64B. However, SGI-1, a genomic island known to be responsible for DT104 multidrug resistance, was not present in all DT104 strains examined in this study: one DT104 strain did not contain SGI-1 but carried a 144 kb plasmid, suggesting possible evolutionary relationships between the two DNA elements in the development of antimicrobial resistance.

Complete genome sequence of Salmonella enterica serovar pullorum RKS5078.

Salmonella enterica serovar Pullorum is a chicken-adapted pathogen, causing pullorum disease. Its strict host adaptation has been suspected to result in gene decay. To validate this hypothesis and identify the decayed genes, we sequenced the complete genome of S. Pullorum RKS5078. We found 263 pseudogenes in this strain and conducted functional analyses of the decayed genes.

[Effect of arsenic trioxide and daunorubicin on procoagulant activity of acute promyelocytic leukemia cells].

OBJECTIVE: To explore the effect of arsenic trioxide (ATO) and daunorubicin (DNR) on phosphatidylserine (PS) exposure and related procoagulant activity of acute promyelocytic leukemia (APL) cells. METHODS: Mononuclear cell and neutrophil isolated from whole blood of 12 healthy volunteers were used as control group while APL cells obtained from 12 newly diagnosed APL patients at First Affiliated Hospital, Harbin Medical University from March 2007 to February 2009 were used as experimental group. APL cells were treated with 1 µmol/L ATO and 1 µmol/L DNR for 24 h. PS exposure of APL cells were measured by flow cytometry and confocal microscopy. And the related procoagulant activity was detected by the assays of coagulation time and coagulation factor formation. Lactadherin was used as a probe for PS exposure and anticoagulant on the cells of 12 APL patients. RESULTS: ATO induced a decrease of PS exposure on APL cells by flow cytometry and no staining with lactadherin was observed under confocal microscopy. However, DNR induced the significantly elevated PS exposure and staining green with a rim pattern on membrane of APL cells was obtained. Coagulation time was (180 ± 25) s and (220 ± 41) s before and after treatment with ATO, respectively (P < 0.05). The formation of coagulation factors decreased after treatment with ATO (P < 0.05). While coagulation time was (180 ± 25) s and (80 ± 20) s before and after treatment with DNR, respectively (P < 0.05). The formation of coagulation factors increased after treatment with DNR (all P < 0.05). Lactadherin inhibited the procoagulant activities of DNR-treated APL cells (all P < 0.05). CONCLUSIONS: Procoagulant activity is positively correlated with the exposed PS of APL cells. ATO and DNR inhibited and enhanced procoagulant activity with decreased and increased PS exposure, respectively.

The Association between Diabetes Complications, Diabetes Distress, and Depressive Symptoms in Patients with Type 2 Diabetes Mellitus.

This study investigated the association between diabetes complications, diabetes distress, and depressive symptoms in patients with type 2 diabetes mellitus. A total of 600 patients with type 2 diabetes mellitus were included in this study. Data were collected using the Diabetes Distress Scale and the nine-item Patient Health Questionnaire. The results showed that both diabetes complications and diabetes distress were positively associated with depressive symptoms, and diabetes distress attenuated the association between diabetes complications and depressive symptoms. The Sobel test confirmed the mediating effect of diabetes distress. Patients with both diabetes complications and diabetes distress had a higher risk of depressive symptoms than those with diabetes complications or diabetes distress alone. This study indicates that the positive association between diabetes complications and depressive symptoms is persistent and mediated by diabetes distress, and the comorbidity of diabetes complications and diabetes distress has an additive interaction effect on depressive symptoms.

Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins.

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.

An optimized RNA amplification method for prokaryotic expression profiling analysis.

DNA microarray technology has been extensively used for gene expression analysis of both eukaryotic and prokaryotic organisms. For eukaryotic gene expression profiling, the poly(A)-based reverse transcription of messenger RNA (mRNA) followed by T7 RNA polymerase-based in vitro transcription is generally required to produce enough RNA targets for hybridization with the microarray chips. However, the same method cannot be directly applied to prokaryotic mRNAs due to the lack of poly(A) sequences at the 3' ends. Conventional methods usually require large amounts of starting RNAs and lead to high background noise. Recently developed amplification methods enable smaller amounts of prokaryotic RNA to be used from samples with species-specific primers, oligo(dT) primers, or random primers. In this study, three target preparation methods, including the direct labeling, polyadenylation-involved oligo-dT priming, and random priming amplification (respectively referred to as DL, PAOD, and RPA hereafter) were evaluated through expression profiling of a heat shock model of Escherichia coli. The PAOD method was found to be more sensitive and more specific in differential gene expression measurements than either DL and RPA, even when the E. coli RNA was only a small proportion of the simulated eukaryotic host RNA. The results suggest that PAOD is the preferred target preparation method for prokaryotic transcriptome.