The causal relationship between CSF metabolites and GBM: a two-sample mendelian randomization analysis.

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor characterized by rapid progression, poor prognosis, and high mortality rates. Understanding the relationship between cerebrospinal fluid (CSF) metabolites and GBM is crucial for identifying potential biomarkers and pathways involved in the pathogenesis of this devastating disease. METHODS: In this study, Mendelian randomization (MR) analysis was employed to investigate the causal relationship between 338 CSF metabolites and GBM. The data for metabolites were obtained from a genome-wide association study summary dataset based on 291 individuals, and the GBM data was derived from FinnGen included 91 cases and 174,006 controls of European descent. The Inverse Variance Weighted method was utilized to estimate the causal effects. Supplementary comprehensive assessments of causal effects between CSF metabolites and GBM were conducted using MR-Egger regression, Weighted Median, Simple Mode, and Weighted Mode methods. Additionally, tests for heterogeneity and pleiotropy were performed. RESULTS: Through MR analysis, a total of 12 identified metabolites and 2 with unknown chemical properties were found to have a causal relationship with GBM. 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), 7-alpha-hydroxy-3-oxo-4-cholestenoate, Alpha-tocopherol, Behenoyl sphingomyelin (d18:1/22:0), Cysteinylglycine, Maleate, Uracil, Valine, X-12,101, X-12,104 and Butyrate (4:0) are associated with an increased risk of GBM. N1-methylinosine, Stachydrine and Succinylcarnitine (c4-dc) are associated with decreased GBM risk. CONCLUSION: In conclusion, this study sheds light on the intricate interplay between CSF metabolites and GBM, offering novel perspectives on disease mechanisms and potential treatment avenues. By elucidating the role of CSF metabolites in GBM pathogenesis, this research contributes to the advancement of diagnostic capabilities and targeted therapeutic interventions for this aggressive brain tumor. Further exploration of these findings may lead to improved management strategies and better outcomes for patients with GBM.

Transcriptome analysis of Reticulitermes flaviceps exposed to Mentha spicata essential oil and carvone indicates a potential neurotoxic mechanism of action characterized by intracellular calcium influx mediated by dopamine receptors.

Reticulitermes flaviceps is an economically important pest in agriculture, forestry, and construction. Recent studies have shown an increase in research focusing on the anti-termite properties of plant essential oils, however, there remains a lack of information regarding the specific molecular mechanism involved. In this study, RNA-seq analysis was conducted on termites exposed to Mentha spicata essential oil (EO) and carvone, leading to the discovery of various genes that were expressed differentially under different treatment conditions. Numerous genes that exhibited a response to M. spicata EO and carvone found to be associated with stress-related pathways, such as drug metabolism cytochrome P450, glutathione metabolism, fatty acid metabolism, citric acid cycle, neuroactive ligand-receptor interaction, cell apoptosis, the AMPK signalling pathway, the mTOR signalling pathway, the longevity regulation pathway, ubiquitin-mediated protein hydrolysis, and the calcium signalling pathway. The up-regulation of genes (SPHK) associated with calcium channels, such as SPHK, indicates a potential mechanism of neurotoxicity, while the up-regulation of apoptosis-associated genes, including ACTB_G1, PYG, SQSTM1, RNF31, suggests a potential mechanism of cytotoxicity. The metabolism of M. spicata EO induces oxidative stress, elevates free Ca2+ levels in mitochondria, and initiates the generation of reactive oxygen species (ROS), ultimately resulting in programmed cell necrosis and apoptosis, as well as facilitating cellular autophagy. The monoterpenes exhibited neurotoxic and cytotoxic effects on R. flaviceps and could be exploited to advance termiticide development and eco-friendly termite control.

Primary robot-assisted laparoscopic partial nephrectomy for hemorrhage secondary to angiomyolipoma: a retrospective study from a large tertiary hospital in China.

With the continuous development of robot-assisted technology, Robot-assisted Laparoscopic Partial Nephrectomy (RALPN) has gradually become an optional method for the treatment of Hemorrhage secondary to angiomyolipoma (HSA). However, there are rare clinical reports of the primary RALPN for HSA. Therefore, this research aims to evaluate the efficacy and safety of primary RALPN for HSA. Fourteen patients(six males and eight females), aged 14-56 years, underwent primary RALPN for HSA and were retrospectively analyzed from 2015 to 2023. The initial blood routine examination revealed decreased hemoglobin in all patients, and Contrast-enhanced computed tomography (CT) indicated retroperitoneal hematoma. After correcting shock and electrolyte imbalance through fluid therapy and medical treatment, all primary RALPN procedures were performed with transabdominal access on the side of the Hemorrhage. After tumor resection and hematoma removal with a monopolar Curved Scissor, the absorbable barbed suture was performed for inner and outer running stitches, respectively. Patient demographic information, perioperative characteristics, and functional outcomes were collected and analyzed. The initial tumor size of fourteen patients ranged from 57 to 145 mm, and the RENAL ranged from 7 to 11. All of the HSA was controlled, and primary RALPN was successful. The operating time it was ranged from 105 to 265 min. Postoperatively, one patient exhibited chylous drainage (Clavien-Dindo II), and another patient developed pleural effusion (Clavien-Dindo III). No postoperative transfusion and Digital Subtraction Angiography (DSA) highly selective embolization of the bleeding vessel was needed. No patients developed urinoma or urinary fistula. Within the follow-up period, the overall complications were manageable. Primary RALPN is a safe and effective procedure for HSA, which may be considered an alternative to selective renal artery embolization.

New clinical insights into the treatment of benign uretero-ileal anastomotic stricture following radical cystectomy and urinary diversion.

BACKGROUND: Benign uretero-ileal anastomotic stricture (UIAS) is a potentially serious complication that can arise after radical cystectomy (RC) and subsequent urinary diversion. To preserve residual renal function and improve prognosis, it is crucial to derive insights from experience and tailor individualized treatment strategies for different patients. PATIENTS AND METHODS: From October 2014 to June 2021, a total of 47 patients with benign UIAS underwent endoscopic management (n = 19) or reimplantation surgery (n = 28). The basic data, perioperative conditions, and postoperative outcomes of the two groups were compared and analyzed to evaluate efficacy. RESULTS: Comparing preoperative and postoperative clinical efficacy within the same group, the endoscopic group showed no significant differences in creatinine and blood urea nitrogen (BUN) levels before surgery or after extubation (p > 0.05). However, significant differences were observed in glomerular filtration rate (GFR) levels on the affected side before surgery and after extubation (p < 0.05). In contrast, the laparoscopic reimplantation group did not exhibit significant differences in creatinine, BUN, or GFR levels of affected side before surgery and after extubation (p > 0.05). Postoperative clinical efficacy showed no significant difference in creatinine and BUN levels between the two groups (p > 0.05). However, GFR values of affected side in the endoscopic treatment group decreased more than those in the laparoscopic reimplantation group (p < 0.05). Additionally, the laparoscopic reimplantation group was able to remove the single-J tube earlier than the endoscopic treatment group (p < 0.05), had a lower recurrence rate of hydronephrosis after extubation (p < 0.05), and experienced a later onset of hydronephrosis compared to the endoscopic treatment group (p < 0.05). CONCLUSIONS: Based on our experience in treating UIAS following RC combined with urinary diversion, laparoscopic reimplantation effectively addresses the issue of UIAS, allowing for the removal of the ureteral stent relatively soon after surgery. This approach maintains long-term ureteral patency, preserves residual renal function, reduces the risk of ureteral restenosis and hydronephrosis, and has demonstrated superior therapeutic outcomes in this study.

Exogenous Janus Kinase 617 Codon Influences Small Noncoding RNAs and Gene Expression in Ba/F3 Cells.

ABSTRACT: Myeloproliferative neoplasms (MPNs) are blood cancers caused by mutations that originate from hematopoietic stem cells. More than 50%-90% of MPN patients had a dominant negative valine (V) to phenylalanine (F) mutation at the Janus kinase 617 codon (JAK2V617F) within the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway; however, this mutation was also found in a high percentage of the general population, its penetrance varied, and its onset was shown to be polygenic. Consequently, it is still unknown what molecular mechanism underlies the MPN transformation produced by JAK2V617F. Patients with MPN have been shown to have dysregulation of noncoding RNAs, such as microRNA (miRNA) and PIWI-interacting RNA (piRNA), although there is not any concrete proof that JAK2V617F alone is responsible for the aberrant regulation of miRNA and piRNA. Human wild type versus V617F-mutated JAK2 are expressed in mouse Ba/F3 cells, and the expressed small and total RNAs were subjected to next generation sequencing analysis to determine the direct induction. Differentially expressed miRNAs, gene expression, and transcript and gene variations were found between exogenously expressed JAK2 and JAK2V617F in Ba/F3 cells. The differently expressed variations contained enriched transposable elements and piRNAs, indicating a rearranged epigenome. The results of the pathway analysis show that the transformation that self-validated the chosen sequencing target genes is impacted by the JAK-STAT pathway. The induction route is functionally conserved, according to exogenously produced miRNA and gene expression. These results may clarify how the JAK2V617F induces transformation.

Negative Affect as a Mediator Between Exposure to Fitspiration and Thinspiration and Disordered Eating Behaviors: An Ecological Momentary Assessment Study.

OBJECTIVE: Although social media use, such as Instagram, has been associated with ED pathology, mechanisms connecting social media use to disordered eating behaviors (DEBs) remain largely unevaluated. Based on Dual Process, Tripartite, and Affect Regulation models of ED pathology, we proposed a moderated mediation model evaluating impacts of exposure to fitspiration/thinspiration on Instagram. METHOD: We evaluated a hypothesized pathway from exposure to fitspiration/thinspiration (i.e., ED-salient content) on Instagram to disordered eating mediated by negative affect and tested individual differences in weight bias internalization, trait self-esteem, and trait self-comparison as moderators. We recruited 173 undergraduate women who reported engaging in DEBs on average at least once per week over the past 3 months. Participants completed a seven-day ecological momentary assessment protocol, during which they reported their ED-salient content exposure on Instagram, affect, and engagement in DEBs. RESULTS: Multilevel modeling was used to assess moderated mediation. Negative affect partially mediated associations between viewing ED-salient content and subsequent engagement in objective binge eating and restricting but did not mediate the pathway to purging or excessive exercise. Higher weight bias internalization intensified the association between viewing ED-salient content and negative affect. DISCUSSION: The association between viewing ED-salient content and engaging in objective binge eating and restricting may be a partial consequence of elevated negative affect; however, effects were small. Individuals with higher weight bias internalization may be more vulnerable to negative consequences from viewing ED-salient content. Findings suggested that reducing negative affect responses (e.g., via emotion regulation) could reduce negative consequences of viewing ED-salient content.

Evaluation of novel synthetic peptides of avian hepatitis E virus ORF2 as vaccine candidate in chickens.

Avian hepatitis E virus (HEV) has resulted in significant economic losses in the poultry industry. There is currently no commercial vaccination available to prevent avian HEV infection. Previously, a novel epitope (601TFPS604) was discovered in the ORF2 protein of avian HEV. In this study, peptides were synthesized and assessed for their ability to provide immunoprotecting against avian HEV infection in poultry. Twenty-five Hy-Line Variety Brown laying hens were randomly divided into five groups; groups 1 to 3 respectively immunized with RLLDRLSRTFPS, PETRRLLDRLSR (irrelevant peptide control), or truncated avian HEV ORF2 protein (aa 339-606), while group 4 (negative control) was mock-immunized with PBS and group 5 (normal control) was not immunized or challenged. After the challenge, all hens in groups 2 and 4 showed seroconversion, fecal virus shedding, viremia, alanine aminotransferase (ALT) level increasing, liver lesions and HEV antigen in the liver. There were no pathogenic effects in other groups. Collectively, all of these findings showed that hens were completely protected against avian HEV infection when they were immunized with the peptide containing TFPS of the avian HEV ORF2 protein.

Field evaluation of oil crop rotations for cadmium remediation and safe vegetable oil production across five sites with varying contamination levels.

Oil crops have the potential to remediate cadmium (Cd)-contaminated farmland while producing safe vegetable oil. However, it is currently unknown whether different oil crops can remediate varying levels of Cd contamination in farmland. This study assessed agricultural fields in southern China contaminated with Cd levels ranging from 0.42 to 10.3 mg/kg. Three representative oilseed crops winter rape, oil sunflower, and peanut were selected for field experiments under two rotation systems. The effects of different rotation systems on remediating various Cd contamination levels were compared to evaluate the feasibility and potential of a two oil crop rotation system. All three crops showed good tolerance to Cd without signs of biomass deficiency. The biomass produced by the rape-oil sunflower and rape-peanut rotation systems was 33.44-459.00 g/ha and 30.64-281.40 g/ha, respectively. The Cd concentration in the oil products obtained complied with existing national and international standards (0.05 mg/kg). The remediation efficiency of the rape-oil sunflower and rape-peanut rotation systems was 1.98-7.37 % and 1.21-4.94 %, respectively. However, the remediation efficiencies and enrichment capacities of both rotation systems were somewhat inhibited by heavy Cd contamination (10.3 mg/kg). Therefore, the agricultural model of rotating two oilseed crops can be implemented in Cd-contaminated farmland at all levels but is more suitable for light to moderate Cd contamination.

Cellulase-responsive hydroxypropyl cellulose-anchored hollow mesoporous silica carriers for pesticide delivery.

In this study, a cellulase-responsive controlled-release formulation (FPR-HMS-HPC) was developed by grafting hydroxypropyl cellulose (HPC) onto fipronil (FPR) loaded hollow mesoporous silica (HMS) nanoparticles via ester linkage. The FPR-HMS-HPC formulation was characterized using scanning and transmission electron microscopies, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The results indicated that FPR-HMS-HPC exhibited a high loading capacity of 10.0 % (w/w) and demonstrated favorable responsiveness to cellulase enzyme. Moreover, its insecticidal efficacy against Reticulitermes flaviceps surpassed that of an equivalent dose of FPR. Toxicology studies showed that the mortality and hatching rates of zebrafish exposed to FPR-HMS-HPC nanoparticles were reduced by >6.5 and 8.0 times, respectively. Thus, HPC-anchored HMS nanoparticles as insecticide delivery systems present a sustainable method for pest control significantly reducing harm to non-target organisms and the environment.

Multi-Metallic Nanosheets Reshaping Immunosuppressive Tumor Microenvironment through Augmenting cGAS-STING Innate Activation and Adaptive Immune Responses for Cancer Immunotherapy.

The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese-doped layered double hydroxide (Mn-LDH) is developed for potent anti-tumor immunity by reversing TME. Mn-LDH is synthesized via a one-step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn-LDH effectively releases Mn2+ and Mg2+ upon exposure to TME with high levels of H+ and H2O2, which activates synthase-stimulator of interferon genes pathway and maintains the cytotoxicity of CD8+ T cells respectively, achieving a cascade-like role in innate and adaptive immunity. The locally administered Mn-LDH facilitated a "hot" network consisting of mature dendritic cells, M1-phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn-LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME-modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next-generation cancer immunotherapy.

Associations Between Weight Discrimination, Eating-Disorder-Related Psychiatric Impairment, and Eating-Disorder Treatment Interest Across the Weight Spectrum.

OBJECTIVE: Only approximately 20% of college students with an eating disorder (ED) seek treatment. One barrier to seeking treatment is weight discrimination. Past research demonstrates that experiencing weight discrimination is associated with increased ED risk and decreased in-person treatment engagement. Weight discrimination may be a particularly relevant treatment barrier for students who have a higher body weight given their higher likelihood of experiencing weight discrimination. METHODS: College students with a probable ED diagnosis (N = 372; Mage = 23.94; 73.12% women, 18.55% men, 6.18% another gender; 11.29% Asian, 4.57% Black, 12.63% Hispanic, 83.60% White, 4.84% Native American, and 0.54% another race) completed an online self-report survey that included the Clinical Impairment Assessment (CIA), Experience of Weight Discrimination (EWD) Scale, and a 0-100 scale to indicate interest in participating in virtual guided self-help ED treatment. RESULTS: Linear regression showed significant positive relationships between weight discrimination and ED-related psychiatric impairment and treatment interest. DISCUSSION: Elevations in CIA scores corroborate past literature that suggested that weight discrimination was positively related to ED psychopathology. Contrary to past research, college students who experienced weight discrimination had greater treatment interest. Students who experience weight discrimination may view virtual self-guided treatment as less weight-stigmatizing due to the "do-it-yourself" approach and no in-person interactions. Findings highlight the potential impacts of weight discrimination on acceptability of ED-related care. Future research is needed to identify ways to reduce weight discrimination and promote weight-inclusive practices in the medical system.

Migration of natural organic matter and Pseudomonas fluorescens-associated polystyrene on natural substrates in aquatic environments.

This study investigated the migration behavior of microplastics (MPs) covered with natural organic matter (NOM) and biofilm on three substrates (silica, Pseudomonas fluorescent and Pseudomonas aeruginosa biofilms) in various ionic strengths, focusing on the alterations in surface properties based on surface energy theory that affected their deposition and release processes. Peptone and Pseudomonas fluorescens were employed to generate NOM-attached and biofilm-coated polystyrene (PS) (NOM-PS and Bio-PS). NOM-PS and Bio-PS both exhibited different surface properties, as increased roughness and particle sizes, more hydrophilic surfaces and altered zeta potentials which increased with ionic strength. Although the deposition of NOM-PS on biofilms were enhanced by higher ionic strengths and the addition of Ca2+, while Bio-PS deposited less on biofilms and more on the silica surface. Both types exhibited diffusion-driven adsorption on the silica surface, with Bio-PS also engaging in synergistic and competitive interactions on biofilm surfaces. Release tests revealed that NOM-PS and Bio-PS were prone to release from silica than from biofilms. The Extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory furtherly demonstrated that mid-range electrostatic (EL) repulsion had significantly impacts on NOM-PS deposition, and structural properties of extracellular polymeric substances (EPS) and substrate could affect Bio-PS migration.

Assessing the distortions introduced when calculating d': A simulation approach.

The discriminability measure d ' is widely used in psychology to estimate sensitivity independently of response bias. The conventional approach to estimate d ' involves a transformation from the hit rate and the false-alarm rate. When performance is perfect, correction methods must be applied to calculate d ' , but these corrections distort the estimate. In three simulation studies, we show that distortion in d ' estimation can arise from other properties of the experimental design (number of trials, sample size, sample variance, task difficulty) that, when combined with application of the correction method, make d ' distortion in any specific experiment design complex and can mislead statistical inference in the worst cases (Type I and Type II errors). To address this problem, we propose that researchers simulate d ' estimation to explore the impact of design choices, given anticipated or observed data. An R Shiny application is introduced that estimates d ' distortion, providing researchers the means to identify distortion and take steps to minimize its impact.

Integration of metagenomics and metaproteomics in the intestinal lavage fluids benefits construction of discriminative model and discovery of biomarkers for HBV liver diseases.

Intestinal lavage fluid (IVF) containing the mucosa-associated microbiota instead of fecal samples was used to study the gut microbiota using different omics approaches. Focusing on the 63 IVF samples collected from healthy and hepatitis B virus-liver disease (HBV-LD), a question is prompted whether omics features could be extracted to distinguish these samples. The IVF-related microbiota derived from the omics data was classified into two enterotype sets, whereas the genomics-based enterotypes were poorly overlapped with the proteomics-based one in either distribution of microbiota or of IVFs. There is lack of molecular features in these enterotypes to specifically recognize healthy or HBV-LD. Running machine learning against the omics data sought the appropriate models to discriminate the healthy and HBV-LD IVFs based on selected genes or proteins. Although a single omics dataset is basically workable in such discrimination, integration of the two datasets enhances discrimination efficiency. The protein features with higher frequencies in the models are further compared between healthy and HBV-LD based on their abundance, bringing about three potential protein biomarkers. This study highlights that integration of metaomics data is beneficial for a molecular discriminator of healthy and HBV-LD, and reveals the IVF samples are valuable for microbiome in a small cohort.

A Broad-specificity Neutralizing Nanobody against Hepatitis E Virus Capsid Protein.

Hepatitis E virus (HEV) is a worldwide zoonotic and public health concern. The study of HEV biology is helpful for designing viral vaccines and drugs. Nanobodies have recently been considered appealing materials for viral biological research. In this study, a Bactrian camel was immunized with capsid proteins from different genotypes (1, 3, 4, and avian) of HEV. Then, a phage library (6.3 × 108 individual clones) was constructed using peripheral blood lymphocytes from the immunized camel, and 12 nanobodies against the truncated capsid protein of genotype 3 HEV (g3-p239) were screened. g3-p239-Nb55 can cross-react with different genotypes of HEV and block Kernow-C1/P6 HEV from infecting HepG2/C3A cells. To our knowledge, the epitope recognized by g3-p239-Nb55 was determined to be a novel conformational epitope located on the surface of viral particles and highly conserved among different mammalian HEV isolates. Next, to increase the affinity and half-life of the nanobody, it was displayed on the surface of ferritin, which can self-assemble into a 24-subunit nanocage, namely, fenobody-55. The affinities of fenobody-55 to g3-p239 were ∼20 times greater than those of g3-p239-Nb55. In addition, the half-life of fenobody-55 was nine times greater than that of g3-p239-Nb55. G3-p239-Nb55 and fenobody-55 can block p239 attachment and Kernow-C1/P6 infection of HepG2/C3A cells. Fenobody-55 can completely neutralize HEV infection in rabbits when it is preincubated with nonenveloped HEV particles. Our study reported a case in which a nanobody neutralized HEV infection by preincubation, identified a (to our knowledge) novel and conserved conformational epitope of HEV, and provided new material for researching HEV biology.

Pathogenicity of two different genotypes avian hepatitis E strains in laying hens and silkie fowl.

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls.

Treatment outcome and germline predictive factors of ropeginterferon alpha-2b in myeloproliferative neoplasm patients.

BACKGROUND: Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking. METHODS: To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases. RESULTS: ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response. CONCLUSIONS: Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

Peripheral Control of the Assembly and Chirality of Anion-Based Octanuclear Cubes by Cation-π Networks.

Self-assembly of sophisticated polyhedral cages has drawn much attention because of their elaborate structures and potential applications. Herein, we report the anion-coordination-driven assembly of the first A8L12 (A = anion, L = ligand) octanuclear cubic structures from phosphate anion and p-xylylene-spaced bis-bis(urea) ligands via peripheral templating of countercations (TEA+ or TPA+). By attaching terminal aryl rings (phenyl or naphthyl) to the ligand through a flexible (methylene) linker, these aryls actively participate in the formation of plenty of "aromatic pockets" for guest cation binding. As a result, multiple peripheral guests (up to 22) of suitable size are bound on the faces and vertices of the cube, forming a network of cation-π interactions to stabilize the cube structure. More interestingly, when chiral ligands were used, either diastereomers of mixed Λ- and Δ-configurations (with TEA+ countercation) for the phosphate coordination centers or enantiopure cubes (with TPA+) were formed. Thus, the assembly and chirality of the cube can be modulated by remote terminal groups and peripheral templating tetraalkylammonium cations.

Examining associations between disordered eating and harmful substance use in a nationally representative sample of US veterans.

OBJECTIVE: The association between eating disorders (EDs) and harmful substance use (substance use that causes psychosocial impairment) is well recognized in the literature, and military veterans may be at heightened risk for both issues due to deployment-related stressors. However, little is known about which ED-related symptoms are associated with harmful substance use in veterans, and whether gender plays a differential role in this relationship. Our aims were to: (1) examine gender differences in ED-related symptoms; and (2) examine whether ED-related symptoms differentially predict harmful substance use in US veteran men and women who had recently separated from service. METHOD: This study was based on a nationally representative four-wave longitudinal sample of post-9/11 veterans (N = 835; 61.2% female). Longitudinal mixed modeling was used to test whether specific ED-related behaviors at baseline predicted harmful substance use at follow-ups. RESULTS: We replicated gendered patterns of ED-related symptoms observed in civilian populations, wherein men had higher weight-and-body-related concerns (including excessive exercise and muscle building) and negative attitude toward obesity, and women had higher bulimic and restricting symptoms. For women, alcohol, drug, and marijuana problems were predicted by higher bulimic symptoms, whereas for men, these problems were predicted by higher restricting symptoms. CONCLUSION: Gender played a differential role in the relationship between EDs and harmful substance use. Bulimic symptoms were the most robust predictor for harmful substance use among veteran women, whereas restricting was the most robust predictor for harmful substance use among veteran men. PUBLIC SIGNIFICANCE: The current study found that veteran women had higher bulimic symptoms (characterized by binge eating and purging) and restricting than veteran men. In women, bulimic symptoms predicted future harmful use of alcohol, marijuana, and other drugs. In contrast, veteran men had higher weight-and-body-related concerns (characterized by excessive exercise and muscle building) than veteran women. In men, restricting symptoms predicted future harmful use of alcohol, marijuana, and other drugs.