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Summary MLL‐rearranged (MLL‐r) leukaemia is observed in approximately 10% of acute myeloid leukaemia (AML) and is associated with a relatively poor prognosis, highlighting the need for new treatment regimens. MLL fusion proteins produced by MLL rearrangements recruit KDM4C to mediate epigenetic reprogramming, which is required for the maintenance of MLL‐r leukaemia. In this study, we used a combinatorial drug screen to selectively identify synergistic treatment partners for the KDM4C inhibitor SD70. The results showed that the drug combination of SD70 and MI‐503, a potent menin‐MLL inhibitor, induced synergistically enhanced apoptosis in MLL::AF9 leukaemia cells without affecting normal CD34+ cells. In vivo treatment with SD70 and MI‐503 significantly prolonged survival in AML xenograft models. Differential gene expression analysis by RNA‐seq following combined pharmacological inhibition of SD70 and MI‐503 revealed changes in numerous genes, with MYC target genes being the most significantly downregulated. Taken together, these data provide preclinical evidence that the combination of SD70 and MI‐503 is a potential dual‐targeted therapy for MLL::AF9 AML. [ABSTRACT FROM AUTHOR]

BACKGROUND: Maltose is an essential derivative of starch. To understand the processability and stability of maltose‐containing foods, material characterization of the phase and state transition from its amorphous state is required. Although the crystallization of amorphous maltose is well understood, few studies have reported the relationship between the crystallization and the glass transition temperature (Tg)‐related molecular mobility. In this study, water sorption, crystallization, Tg‐related α‐relaxation, and the corresponding time factor for amorphous maltose and maltose / whey protein isolate (WPI) mixtures are measured at various water activity (aw) levels and 25 °C. RESULTS: The water‐additive principle for maltose / WPI mixtures was observed at aw ≤ 0.440 at the molecular level, whereas the crystallization of amorphous maltose occurred at high aw values (≥0.534). The crystal formation and crystallization kinetics of amorphous maltose were affected by water and WPI at aw ≥ 0.534 and 25 °C, as determined by X‐ray diffraction. The relationship between Tg and the water content was fitted by the Gordon–Taylor model, and its constant showed a compositional dependence for the maltose / WPI mixtures. The α‐relaxation temperature of the amorphous samples decreased due to water plasticization, but increased with an increase in the WPI quantity. The Strength (S) value for amorphous maltose, which was a quantitative estimate of the compositional effects on molecular mobility, was based on the William–Landel–Ferry (WLF) equation. CONCLUSION: The S concept exhibits considerable potential for application in controlling the crystallization of amorphous maltose and improving the processability and stability of maltose‐containing foods. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

We propose a new rank-based goodness-of-fit test for copulas. It uses the information matrix equality and so relates to the White (1982) specification test. The test avoids parametric specification of marginal distributions, it does not involve kernel weighting, bandwidth selection, or any other strategic choices, it is asymptotically pivotal with a standard distribution, and it is simple to compute compared to available alternatives. The finite-sample size of this type of tests is known to deviate from their nominal size based on asymptotic critical values, and bootstrapping critical values could be a preferred alternative. A power study shows that, in a bivariate setting, the test has reasonable properties compared to its competitors. We conclude with an application in which we apply the test to two stock indices. [ABSTRACT FROM AUTHOR]

This thesis reviews the development of family therapy in Taiwan since its commence in 1969 to today, with two focuses on the status quo in practice and in training. The practice of family therapy in local hospitals, social welfare agencies and community counseling institutes are reviewed respectively, with a discussion of the challenges local family therapists encounter. The status quo of local family therapy trainings is also examined in terms of trainers, programs, professional organizations and licensure. The limitations and possible hindrances to the current professional training system are explored, and finally suggestions for the advance of local family therapy professional development in Taiwan are proposed. [ABSTRACT FROM AUTHOR]

• A fluorescent ratiometric sensor (TPAI) was designed for detecting Zn2+with the low detection limit (4.16 nM). • The "green-to-red" color transition of TPAI was very suitable for human visible system. • A simple immersion method was provided for rapid evaluating the battery pollution. The leakage of hazardous substances from batteries leads amount of pollution events for their high toxicity and universal use all over the world. Herein, a fluorescent sensor based on triphenylamine (TPAI) was designed to monitor the battery pollution in the real soil examples. Because Zn2+composes a large part of primary and secondary batteries, TPAI was constructed for high affinity of Zn2+ within an efficient intramolecular charge transfer process that could output an obvious green-to-red (510–600 nm) signal to avoid interference from the background substances. In this way, TPAI showed a low detection limit (4.16 × 10−9 M) and high binding constants towards Zn2+ (2.82 × 1012 M−1). Moreover, TPAI exhibited excellent selectivity for Zn2+ over other metal ions and several common compounds in soil. The sensing mechanism indicated that the selectivity might need to be further optimized through adjusting the bulk of donor segment of TPAI. Then, TPAI was used to discriminate the polluted and unpolluted soil samples through a feasible on-line detection proposal under the self-made mobile platform. Combining with the fluorescent sensors and our mobile platform, we believe this work can provide a practical tool for monitoring the pollution events in diverse environmental examples. A ratiometric sensor (TPAI) for responsing to Zn(II) was designed with obvious traffic light transform (green-to-red) based on the suitable change in its intramolecular change transfer. Through optimizing the working mediums, we successfully used the "green solvent", ethanol, to monitor the battery-pollution event in soil samples. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most aggressive type of head and neck cancer with an unsatisfactory 5‐year survival rate. MicroRNAs are a group of small noncoding RNAs reported to serve important roles in carcinogenesis, inhibiting certain gene expression via targeting the 3′‐untranslated region of messenger RNAs (mRNAs). MiR‐4282 has been newly discovered to be a tumor suppressor in colorectal cancer, but it has never been studied in OSCC. The present study aimed to uncover the role of miR‐4282 in OSCC. We first confirmed that miR‐4282 was downregulated in OSCC and validated its prognostic significance. Through gain‐of‐function assays, miR‐4282 was discovered to inhibit proliferation, migration, and epithelial‐to‐mesenchymal transition, and induce apoptosis. By mechanistic research, we predicted via bioinformatics tools and confirmed by luciferase reporter and pulldown assays that miR‐4282 targeted LIN28B, an RNA‐binding protein, which has been reported to regulate RNA stability in cancers. Furthermore, we confirmed the interaction between LIN28B and zinc finger and BTB domain containing 2 (ZBTB2), and validated that miR‐4282 regulated mRNA stability of ZBTB2 by inhibiting LIN28B. Rescue assays proved that miR‐4282 inhibited tumor progression through LIN28B/ZBTB2 axis. In vivo assays proved that miR‐4282 inhibited tumor growth in OSCC. In conclusion, the present study revealed that miR‐4282 inhibited tumor progression through downregulation of ZBTB2 by targeting LIN28B in OSCC cells, indicating miR‐4282 as a novel biomarker for OSC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lactose/WPI composite hydrocolloids were considered as ink materials in 3D printing. • Lactose-derived co-solvation can help to avoid WPI aggregation and enhance fluidness. • Shearing and mechanical τ can be modelled by WLF with material-special constants. • Fluidness measures flow property and gives an "printable indicator" for hydrocolloids. In this study, the lactose/Whey Protein Isolate (WPI) composite hydrocolloids were prepared as an printing material for subsequent 3D printing. The results showed that the rheological, viscoelastic, thermal and mechanical properties of the studied hydrocolloids were composition dependent, which was directly linked to the printing fidelity of printed objects. The morphology of all printed objects showed a porous microstructure, and their porosity was changed by lactose addition. This outcome resulted from lactose-derived co-solvation discouraging WPI aggregation during the printing process, which was necessary for improving printing performance. Moreover, an innovative Fluidness concept (F), using material-specific WLF analysis of relaxation times, was introduced to quantify the fluidness of lactose/ WPI composite hydrocolloids at a certain decay of timescales (from 102 to 10-3 s). This F concept was superior for the description and control of printing fidelity, dimensional deviation, and textural properties of 3D -printed objects. Therefore, the F concept is a "printable indicator" for dairy by-products that may possess proper printability and provides an alternative approach to make attractive designs for 3D printing foods. [ABSTRACT FROM AUTHOR]

Objective: Circulating tumor DNA (ctDNA) is emerging as a versatile biomarker for noninvasive genotyping and response monitoring in specific B‐cell lymphomas; however, few studies have been conducted to explore ctDNA‐based mutation profiling across non‐Hodgkin lymphomas (NHLs) and genomic changes after initiation of chemotherapy. Methods: A targeted sequencing of 362 genes was performed to detect the mutation profiles in paired blood and tissue samples from 42 NHL patients. Genomic alterations were explored in 11 diffuse large B‐cell lymphoma (DLBCL) patients using paired blood samples collected pre‐ and post‐R‐CHOP chemotherapy. Results: The frequencies of PIM1, MYD88, MYC, ZNF292, JAK, and MAF mutations were higher in aggressive than in indolent B‐cell lymphoma and NK/T subtypes. Tumor mutation burden in blood samples was higher in aggressive than in indolent B‐cell lymphomas and higher in patients who progressed than in those who responded to treatments. Our data also revealed significant enhance of concordance index through integrating mutated genes that were significantly associated with prognosis into International Prognostic Index‐based prognostic model. Moreover, acquisition of mutations such as PCLO_p.L1220Tfs*3 was associated with resistance to R‐CHOP in DLBCL patients. Conclusions: Our findings illustrated distinct mutation patterns across various NHL subtypes and suggested the association of genomic alterations in ctDNA with treatment outcomes. [ABSTRACT FROM AUTHOR]

The characteristics and survival of 218 patients with extranodal natural killer/T-cell lymphoma (ENKTCL) were analyzed in this retrospective study. The median progression-free survival (PFS) and overall survival (OS) were 10.9 months and 50.5 months, respectively. Sequential chemoradiotherapy achieved a 74.5% overall response rate (ORR) and a 30.9% 5-year PFS rate in patients with localized stage. Asparaginase-containing protocols demonstrated superior prognosis in advanced cases, with a median FPS at 5.7 months, compared to 1.9 months without asparaginase. Initial treatment with P-GEMOX regimens showed superior ORR and PFS compared to the SMILE regimen, with lower toxicities. Hematopoietic stem cell transplantation (HSCT) improved the PFS and OS of refractory or relapsed (R/R) cases. PD-1/PD-L1 antibody could achieve a median PFS at 4.0 months and a median OS at 14.6 months in R/R patients for whom salvage therapies failed. High-risk PINK-E score was the only independent adverse prognostic factor for PFS and OS. [ABSTRACT FROM AUTHOR]

Background: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. Methods: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). Results: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. Conclusion: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate. [ABSTRACT FROM AUTHOR]

Social deficits are features of autism and highly heritable traits. A common variant in autism-related CNTNAP2 gene, rs2710102, has been linked with social performance, but the neural substrates are largely unknown. We investigated variations in social performance and functional connectivity (static and dynamic) in the subregions of right temporoparietal junction (RTPJ), a key node of brain social network, using resting-state magnetic resonance imaging (n  = 399) by genotype at rs2710102 in healthy volunteers. Social performance was evaluated using the social domain of the Autism-Spectrum Quotient (AQ-social; n  = 641) and fixation time on eye areas during an eye-tracking task (n  = 32). According to previous evidence that the A-allele is the risk allele for social dysfunction, we classified participants into GG and A-allele carriers (AA/AG) groups. The A-allele carriers showed poor social performance (high AQ-social and short fixation time on eye areas) compared with the GG carriers. In the A-allele carriers, decreased stationary functional connectivity between the orbitofrontal cortex and posterior RTPJ (pRTPJ), and decreased dynamic functional connectivity (dFC) between the medial prefrontal cortex (mPFC) and pRTPJ were observed. The fixation time at eye areas positively were correlated with the pRTPJ-mPFC dFC. These findings provided insight for genetic effect on social behavior and its potential neural substrate. [ABSTRACT FROM AUTHOR]

Highlights: [•] Interleukin(IL)-32 was overexpressed in lung adenocarcinoma tissues and cell lines. [•] IL-32 expression correlated with tumor metastasis, and leads to poor prognosis. [•] Ectopic expression of IL-32 facilitated invasion and migration of tumor cells. [•] IL-32-induced metastasis was via MMP2 and MMP9 upregulation through NF-κB pathway. [Copyright &y& Elsevier]

• The rs2710102 GG and rs7794745 TT allele carriers show smaller temporal cortex volume in the 442 high homogeneity participants, respectively. • Smaller volume of right parahippocampal, right STG, and left IPL cortex was correlated to high autistic traits related to social skills. • The indirect effects of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance were mediated by temporal cortex. Autistic traits are highly heritable and characterized by social deficits. Common genetic variants of the autism-related CNTNAP2 gene have been linked with social impairments, but the neural substrates are poorly understood. In the present study, we investigated the genetic effect of common variants of CNTNAP2 (rs2710102 and rs7794745) on gray matter volume and its association with social performance among 442 healthy participants. Our results showed that individuals with rs2710102 GG homozygotes had smaller left superior temporal gyrus (STG)/insular volume than A-allele carriers (AA and AG), while individuals with rs7794745 TT and AT showed smaller right parahippocampal, right STG/insular, and left inferior parietal lobule (IPL) cortex volume than those with rs7794745 AA. Smaller volume of the STG/insular and parahippocampal cortex was associated with poorer social performance. An indirect effect of CNTNAP2 rs7794745 and rs2710102 genotype on the social performance was mediated by the STG/insular cortex and parahippocampal cortex volume. These findings provided insight into the genetic effect of CNTNAP2 variants on social behavior, which may be moderated by the temporal cortex. [ABSTRACT FROM AUTHOR]