Anion-π interactions suppress phase impurities in FAPbI3 solar cells.

Achieving both high efficiency and long-term stability is the key to the commercialization of perovskite solar cells (PSCs)1,2. However, the diversity of perovskite (ABX3) compositions and phases makes it challenging to fabricate high-quality films3-5. Perovskite formation relies on the reaction between AX and BX2, whereas most conventional methods for film-growth regulation are based solely on the interaction with the BX2 component. Herein, we demonstrate an alternative approach to modulate reaction kinetics by anion-π interaction between AX and hexafluorobenzene (HFB). Notably, these two approaches are independent but work together to establish 'dual-site regulation', which achieves a delicate control over the reaction between AX and BX2 without unwanted intermediates. The resultant formamidinium lead halides (FAPbI3) films exhibit fewer defects, redshifted absorption and high phase purity without detectable nanoscale δ phase. Consequently, we achieved PSCs with power conversion efficiency (PCE) up to 26.07% for a 0.08-cm2 device (25.8% certified) and 24.63% for a 1-cm2 device. The device also kept 94% of its initial PCE after maximum power point (MPP) tracking for 1,258 h under full-spectrum AM 1.5 G sunlight at 50 ± 5 °C. This method expands the range of chemical interactions that occur in perovskite precursors by exploring anion-π interactions and highlights the importance of the AX component as a new and effective working site to improved photovoltaic devices with high quality and phase purity.

A Prelimbic Cortex-Thalamus Circuit Bidirectionally Regulates Innate and Stress-Induced Anxiety-Like Behavior.

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PL-mediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders.

Regulators of early maize leaf development inferred from transcriptomes of laser capture microdissection (LCM)-isolated embryonic leaf cells.

The superior photosynthetic efficiency of C4 leaves over C3 leaves is owing to their unique Kranz anatomy, in which the vein is surrounded by one layer of bundle sheath (BS) cells and one layer of mesophyll (M) cells. Kranz anatomy development starts from three contiguous ground meristem (GM) cells, but its regulators and underlying molecular mechanism are largely unknown. To identify the regulators, we obtained the transcriptomes of 11 maize embryonic leaf cell types from five stages of pre-Kranz cells starting from median GM cells and six stages of pre-M cells starting from undifferentiated cells. Principal component and clustering analyses of transcriptomic data revealed rapid pre-Kranz cell differentiation in the first two stages but slow differentiation in the last three stages, suggesting early Kranz cell fate determination. In contrast, pre-M cells exhibit a more prolonged transcriptional differentiation process. Differential gene expression and coexpression analyses identified gene coexpression modules, one of which included 3 auxin transporter and 18 transcription factor (TF) genes, including known regulators of Kranz anatomy and/or vascular development. In situ hybridization of 11 TF genes validated their expression in early Kranz development. We determined the binding motifs of 15 TFs, predicted TF target gene relationships among the 18 TF and 3 auxin transporter genes, and validated 67 predictions by electrophoresis mobility shift assay. From these data, we constructed a gene regulatory network for Kranz development. Our study sheds light on the regulation of early maize leaf development and provides candidate leaf development regulators for future study.

Dopamine D2 receptors in pyramidal neurons in the medial prefrontal cortex regulate social behavior.

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.

Clinical implications of additional chromosomal abnormalities in adult acute myeloid leukemia with inv (16)/t(16;16)/CBFB::MYH11.

OBJECTIVES: This study assesses the clinical significance of additional cytogenetic abnormalities (ACAs) and/or the deletion of 3'CBFB (3'CBFBdel) resulting in unbalanced CBFB::MYH11 fusion in acute myeloid leukemia (AML) with inv (16)/t(16;16)/CBFB::MYH11. METHODS: We retrospectively evaluated the clinicopathologic features of 47 adult de novo AML with inv (16)/t(16;16)/CBFB::MYH11 fusion. There were 44 balanced and 3 unbalanced CBFB::MYH11 fusions. Given the low frequency of unbalanced cases, the latter group was combined with 19 published cases (N = 22) for statistic and meta-analysis. RESULTS: Both balanced and unbalanced cases were characterized by frequent ACAs (56.5% and 72.7%, respectively), with +8, +22, and del(7q) as the most frequent abnormalities. The unbalanced group tends to be younger individuals (p = .04) and is associated with a lower remission rate (p = .02), although the median overall survival (OS) was not statistically different (p = .2868). In the balanced group, "ACA" subgroup had higher mortality (p = .013) and shorter OS (p = .011), and patients with relapsed disease had a significantly shorter OS (p = .0011). Cox multivariate regression analysis confirmed that ACAs and history of disease relapse are independent risk factors, irrespective of disease relapse status. In the combined cohort, cases with ACAs had shorter OS than those with "Sole" abnormality (p = .0109). CONCLUSIONS: ACAs are independent high-risk factors in adult AML with inv (16)/t(16;16)/CBFB::MYH11 fusion and should be integrated for risk stratification in this disease. Larger studies are needed to assess the clinical significance of the unbalanced CBFB::MYH11 fusion resulting from the 3'CBFBdel.

Production improvement of an antioxidant in cariogenic Streptococcus mutans UA140.

AIMS: This study aimed to improve the production of mutantioxidin, an antioxidant encoded by a biosynthetic gene cluster (mao) in Streptococcus mutans UA140, through a series of optimization methods. METHOD AND RESULTS: Through the construction of mao knockout strain S. mutans UA140∆mao, we identified mutantioxidin as the antioxidant encoded by mao and verified its antioxidant activity through a reactive oxygen species (ROS) tolerance assay. By optimizing the culture medium and fermentation time, 72 h of fermentation in chemically defined medium (CDM) medium was determined as the optimal fermentation conditions. Based on two promoters commonly used in Streptococcus (ldhp and xylS1p), eight promoter refactoring strains were constructed, nevertheless all showed impaired antioxidant production. In-frame deletion and complementation experiments demonstrated the positive regulatory role of mao1 and mao2, on mao. Afterward, the mao1 and mao2, overexpression strain S. mutans UA140/pDL278:: mao1mao2, were constructed, in which the production of mutantioxidin was improved significantly. CONCLUSIONS: In this study, through a combination of varied strategies such as optimization of fermentation conditions and overexpression of regulatory genes, production of mutantioxidin was increased by 10.5 times ultimately.

LN-439A, a novel BAP1 inhibitor, suppresses the growth of basal-like breast cancer by degrading KLF5.

Basal-like breast cancer (BLBC) is the most malignant subtype of breast cancer because of its aggressive clinical behaviour and lack of effective targeted agents. Krüppel-like factor 5 (KLF5) is an oncogenic transcription factor that is highly expressed in BLBC. The deubiquitinase (DUB) BRCA1-associated protein 1 (BAP1) stabilizes KLF5 and promotes BLBC growth and metastasis. Therefore, pharmacological inhibition of the BAP1‒KLF5 axis is an effective therapeutic strategy for BLBC. Here, through screening, we identified a series of tetrahydro-ß-carboline derivatives that effectively reduced the protein expression of KLF5 and exhibited strong antitumour activity. Among the investigated compounds, the lead compound LN-439A presented the strongest antitumour activity and inhibitory effect on KLF5 expression. LN-439A suppressed the proliferation and migration of BLBC cells, induced G2/M arrest, and induced apoptosis. Mechanistically, LN-439A functions as a small molecule catalytic inhibitor of BAP1 by binding to the catalytic pocket of BAP1, leading to the ubiquitination and degradation of KLF5. Consistent with this finding, the overexpression of KLF5 suppressed the antitumour effects of LN-439A. In summary, LN-439A is a promising therapeutic agent for BLBC that functions by targeting the BAP1‒KLF5 axis.

Characterization of the ADP-ß-D-manno-heptose biosynthetic enzymes from two pathogenic Vibrio strains.

ADP-activated ß-D-manno-heptoses (ADP-ß-D-manno-heptoses) are precursors for the biosynthesis of the inner core of lipopolysaccharide in Gram-negative bacteria. Recently, ADP-D-glycero-ß-D-manno-heptose (ADP-D,D-manno-heptose) and its C-6'' epimer, ADP-L-glycero-ß-D-manno-heptose (ADP-L,D-manno-heptose), were identified as potent pathogen-associated molecular patterns (PAMPs) that can trigger robust innate immune responses. Although the production of ADP-D,D-manno-heptose has been studied in several different pathogenic Gram-negative bacteria, current knowledge of ADP-ß-D-manno-heptose biosynthesis in Vibrio strains remains limited. Here, we characterized the biosynthetic enzymes of ADP-D,D-manno-heptose and the epimerase that converts it to ADP-L,D-manno-heptose from Vibrio cholerae (the causative agent of pandemic cholera) and Vibrio parahaemolyticus (non-cholera pathogen causing vibriosis with clinical manifestations of gastroenteritis and wound infections) in comparison with their isozymes from Escherichia coli. Moreover, we discovered that ß-D-mannose 1-phosphate, but not α-D-mannose 1-phosphate, could be activated to its ADP form by the nucleotidyltransferase domains of bifunctional kinase/nucleotidyltransferases HldEVC (from V. cholerae) and HldEVP (from V. parahaemolyticus). Kinetic analyses of the nucleotidyltransferase domains of HldEVC and HldEVP together with the E. coli-derived HldEEC were thus carried out using ß-D-mannose 1-phosphate as a mimic sugar substrate. Overall, our works suggest that V. cholerae and V. parahaemolyticus are capable of synthesizing ADP-ß-D-manno-heptoses and lay a foundation for further physiological function explorations on manno-heptose metabolism in Vibrio strains. KEY POINTS: • Vibrio strains adopt the same biosynthetic pathway as E. coli in synthesizing ADP-ß-D-manno-heptoses. • HldEs from two Vibrio strains and E. coli could activate ß-D-mannose 1-phosphate to ADP-ß-D-mannose. • Comparable nucleotidyltransfer efficiencies were observed in the kinetic studies of HldEs.

Development of a xylose-inducible and glucose-insensitive expression system for Parageobacillus thermoglucosidasius.

Inducible expression systems are pivotal for governing gene expression in strain engineering and synthetic biotechnological applications. Therefore, a critical need persists for the development of versatile and efficient inducible expression mechanisms. In this study, the xylose-responsive promoter xylA5p and its transcriptional regulator XylR were identified in Parageobacillus thermoglucosidasius DSM 2542. By combining promoter xylA5p with its regulator XylR, fine-tuning the expression strength of XylR, and reducing the glucose catabolite repression on xylose uptake, we successfully devised a xylose-inducible and glucose-insensitive expression system, denoted as IExyl*. This system exhibited diverse promoter strengths upon induction with xylose at varying concentrations and remained unhindered in the presence of glucose. Moreover, we showed the applicability of IExyl* in P. thermoglucosidasius by redirecting metabolic flux towards riboflavin biosynthesis, culminating in a 2.8-fold increase in riboflavin production compared to that of the starting strain. This glucose-insensitive and xylose-responsive expression system provides valuable tools for designing optimized biosynthetic pathways for high-value products and facilitates future synthetic biology investigations in Parageobacillus. KEY POINTS: • A xylose-inducible and glucose-insensitive expression system IExyl* was developed. • IExyl* was applied to enhance the riboflavin production in P. thermoglucosidasius • A tool for metabolic engineering and synthetic biology research in Parageobacillus strains.

Synthetic robust perfect adaptation achieved by negative feedback coupling with linear weak positive feedback.

Unlike their natural counterparts, synthetic genetic circuits are usually fragile in the face of environmental perturbations and genetic mutations. Several theoretical robust genetic circuits have been designed, but their performance under real-world conditions has not yet been carefully evaluated. Here, we designed and synthesized a new robust perfect adaptation circuit composed of two-node negative feedback coupling with linear positive feedback on the buffer node. As a key feature, the linear positive feedback was fine-tuned to evaluate its necessity. We found that the desired function was robustly achieved when genetic parameters were varied by systematically perturbing all interacting parts within the topology, and the necessity of the completeness of the topological structures was evaluated by destroying key circuit features. Furthermore, different environmental perturbances were imposed onto the circuit by changing growth rates, carbon metabolic strategies and even chassis cells, and the designed perfect adaptation function was still achieved under all conditions. The successful design of a robust perfect adaptation circuit indicated that the top-down design strategy is capable of predictably guiding bottom-up engineering for robust genetic circuits. This robust adaptation circuit could be integrated as a motif into more complex circuits to robustly implement more sophisticated and critical biological functions.

Assessment of sources and health risks of heavy metals in metropolitan household dust among preschool children: The LEAPP-HIT study.

The most common construction material used in Taiwan is concrete, potentially contaminated by geologic heavy metals (HMs). Younger children spend much time indoors, increasing HM exposure risks from household dust owing to their behaviors. We evaluated arsenic (As), cadmium (Cd), and lead (Pb) concentrations in fingernails among 280 preschoolers between 2017 and 2023. We also analyzed HM concentrations, including As, Cd, Pb, chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), iron (Fe), and manganese (Mn), in 90 household dust and 50 road dust samples from a residential area where children lived between 2019 and 2021 to deepen the understanding of sources and health risks of exposure to HMs from household dust. The average As, Cd, and Pb concentrations in fingernails were 0.12 ± 0.06, 0.05 ± 0.05, and 0.95 ± 0.77 µg/g, respectively. Soil parent materials, indoor construction activities, vehicle emissions, and mixed indoor combustion were the pollution sources of HMs in household dust. Higher Cr and Pb levels in household dust may pose non-carcinogenic risks to preschoolers. Addressing indoor construction and soil parent materials sources is vital for children's health. The finding of the present survey can be used for indoor environmental management to reduce the risks of HM exposure and avoid potential adverse health effects for younger children.

Can a "Pandemic Life Adaptation" Digital Technology Curriculum Reduce the Digital Disadvantage of Older Adults During COVID-19? An Intervention Study from Shanghai.

Older adults are at a digital disadvantage because of social stereotypes and a lack of social support; however, smartphones have become a necessary technology to cope with crises and daily life in China, especially during the pandemic. This study aimed to help marginalized older adults take on new tasks by developing digital technology education that used a framework of social cognitive theory in social work. The study followed a quasi-experimental design in which 153 elderly people were recruited from three community service centers; 90 of the participants received 6-weekly intervention. Intent-to-treat analysis, effect size calculations, and sensitivity analysis were conducted. The findings show that digital education significantly enhanced two domains of digital life adaptation abilities: general digital life adaptation abilities [g = .50, 95% CI (.70, 2.69)] and pandemic digital life adaptation abilities [g = .89, 95% CI (.96, 2.07)]. The intervention also improved three domains of digital self-efficacy: sharing and communication [g = .55, 95% CI (.04, .48)], verification [g = .34, 95% CI (.01, .59)], and influencing others [g = .53, 95% CI (.13, .77)]. The study showed that the new intervention approach reduced the harm to vulnerable older adults in the digital wave, especially during the pandemic.

MAT1A Suppression by the CTBP1/HDAC1/HDAC2 Transcriptional Complex Induces Immune Escape and Reduces Ferroptosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a significant health burden globally due to its high prevalence and morbidity. C-terminal-binding protein 1 (CTBP1) is a transcriptional corepressor that modulates gene transcription by interacting with transcription factors or chromatin-modifying enzymes. High CTBP1 expression has been associated with the progression of various human cancers. In this study, bioinformatics analysis suggested the existence of a CTBP1/histone deacetylase 1 (HDAC1)/HDAC2 transcriptional complex that regulates the expression of methionine adenosyltransferase 1A (MAT1A), whose loss has been associated with ferroptosis suppression and HCC development. Thus, this study aims to investigate the interactions between the CTBP1/HDAC1/HDAC2 complex and MAT1A and their roles in HCC progression. First, high expression of CTBP1 was observed in HCC tissues and cells, where it promoted HCC cell proliferation and mobility while inhibiting cell apoptosis. CTBP1 interacted with HDAC1 and HDAC2 to suppress the MAT1A transcription, and silencing of either HDAC1 or HDAC2 or overexpression of MAT1A led to the inhibition of cancer cell malignancy. In addition, MAT1A overexpression resulted in increased S-adenosylmethionine levels, which promoted ferroptosis of HCC cells directly or indirectly by increasing CD8+ T-cell cytotoxicity and interferon-γ production. In vivo, MAT1A overexpression suppressed growth of CTBP1-induced xenograft tumors in mice while enhancing immune activity and inducing ferroptosis. However, treatment with ferrostatin-1, a ferroptosis inhibitor, blocked the tumor-suppressive effects of MAT1A. Collectively, this study reveals that the CTBP1/HDAC1/HDAC2 complex-induced MAT1A suppression is liked to immune escape and reduced ferroptosis of HCC cells.

Recent advances in gut microbiota-associated natural products: structures, bioactivities, and mechanisms.

Covering: 2014 to June 2022The gut microbiota has attracted increasing attention from researchers due to its critical role in regulating human physiology and pathophysiology. Natural products (NPs) produced or transformed by gut microbes are key signalling mediators for a variety of physiological functions. On the other hand, NPs from ethnomedicines have also been found to generate health benefits through modulation of the gut microbiota. In this highlight, we review the most recent studies related to gut microbiota-derived NPs and bioactive NPs that regulate physiological and pathological processes via gut microbiota-associated mechanisms. We also outline the strategies for the discovery of gut microbiota-derived NPs and the methodologies of how to elucidate the crosstalk between bioactive NPs and the gut microbiota.

PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction.

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.

Characterization of three succinyl-CoA acyltransferases involved in polyketide chain assembly.

Polyketides are a class of natural products with astonishing structural diversities, fascinating biological activities, and a versatile of applications. In polyketides biosynthesis, acyltransferases (ATs) are the 'gatekeeping' enzymes selecting the specific CoA-activated acyl groups as building blocks and transferring them onto the phosphopantetheine arm of acyl carrier proteins (ACPs) to enable the following condensation reactions to assemble the polyketide chain. Herein, the Art2 protein from aurantinins, a group of the antibacterial polyketides, is characterized in vitro as an AT that can load a CoA-activated succinyl unit onto the first ACP domain of Art17 (ACPArt17-1). In addition, another two proteins, GbnB and EtnB, involved in the biosynthesis of gladiolin and etnangien respectively, were traced by literature mining, homologous searching, and product structure analysis and then identified as functional succinyl-CoA ATs by the ACPArt17-1 assays. Taken together, by the assay method employing ACPArt17-1 as an acyl acceptor, we identified three ATs that can introduce a succinyl unit into the polyketide assembly line, which enriches the toolbox of polyketide biosynthetic enzymes and sets a stage for incorporating a succinyl unit into polyketide backbones in synthetic biological manners. KEY POINTS: • Three acyltransferases that are able to load ACP with a succinyl unit were characterized in vitro. • ACPArt17-1 can be used as an acceptor to assay succinyl-CoA AT from different polyketides. • The succinyl unit can be incorporated into polyketides assembly process.

Molecular asymmetry in the cephalochordate embryo revealed by single-blastomere transcriptome profiling.

Studies in various animals have shown that asymmetrically localized maternal transcripts play important roles in axial patterning and cell fate specification in early embryos. However, comprehensive analyses of the maternal transcriptomes with spatial information are scarce and limited to a handful of model organisms. In cephalochordates (amphioxus), an early branching chordate group, maternal transcripts of germline determinants form a compact granule that is inherited by a single blastomere during cleavage stages. Further blastomere separation experiments suggest that other transcripts associated with the granule are likely responsible for organizing the posterior structure in amphioxus; however, the identities of these determinants remain unknown. In this study, we used high-throughput RNA sequencing of separated blastomeres to examine asymmetrically localized transcripts in two-cell and eight-cell stage embryos of the amphioxus Branchiostoma floridae. We identified 111 and 391 differentially enriched transcripts at the 2-cell stage and the 8-cell stage, respectively, and used in situ hybridization to validate the spatial distribution patterns for a subset of these transcripts. The identified transcripts could be categorized into two major groups: (1) vegetal tier/germ granule-enriched and (2) animal tier/anterior-enriched transcripts. Using zebrafish as a surrogate model system, we showed that overexpression of one animal tier/anterior-localized amphioxus transcript, zfp665, causes a dorsalization/anteriorization phenotype in zebrafish embryos by downregulating the expression of the ventral gene, eve1, suggesting a potential function of zfp665 in early axial patterning. Our results provide a global transcriptomic blueprint for early-stage amphioxus embryos. This dataset represents a rich platform to guide future characterization of molecular players in early amphioxus development and to elucidate conservation and divergence of developmental programs during chordate evolution.

Chitinase 3-like-1 Expression in the Microenvironment Is Associated with Neutrophil Infiltration in Bladder Cancer.

Bladder cancer is a common cancer with well-established therapeutic strategies. However, recurrence occurs in 50% of patients with non-muscle-invasive bladder cancer, and 20% of patients progress to muscle-invasive bladder cancer. The 5-year survival rate for muscle-invasive bladder cancer patients is disappointingly low, ranging from 36% to 48%. A molecular marker of interest is chitinase 3-like-1 (CHI3L1), which is elevated in various cancers, including bladder cancer. In addition to its role in cancer cells, CHI3L1 also has regulatory abilities in immune cells. Neutrophil infiltration has been shown to positively correlate with overall survival, progression-free survival, and relapse-free survival in bladder cancer patients. However, the relationship between CHI3L1 and neutrophils remain poorly understood. Therefore, this study investigated the relationship between CHI3L1 level and protumor neutrophil infiltration in bladder cancer. We analyzed the GSE128959 dataset and the data of a bladder cancer cohort undergoing chemotherapy. We observed higher expression of CHI3L1 in bladder cancer patients with invasive or chemotherapy-resistance. Our results revealed a positive correlation between CHI3L1 expression and protumor neutrophil infiltration. Elevated CHI3L1 expression was associated with genes which were related to the recruitment and infiltration of neutrophils. Consequently, CHI3L1 may serve as a novel evaluation factor for the degree of neutrophil infiltration in advanced bladder cancer in those scheduled for chemotherapy.

Comparison of myeloid neoplasms with nonclassic 3q26.2/MECOM versus classic inv(3)/t(3;3) rearrangements reveals diverse clinicopathologic features, genetic profiles, and molecular mechanisms of MECOM activation.

MECOM rearrangements are recurrent in myeloid neoplasms and associated with poor prognosis. However, only inv(3)(q21q26.2) and t(3;3)(q21;q26.2), the classic MECOM rearrangements resulting in RPN1-MECOM rearrangement with Mecom overexpression and GATA2 haploinsufficiency, define the distinct subtype of acute myeloid leukemia (AML), and serve as presumptive evidence for myelodysplastic syndrome based on the current World Health Organization classification. Myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements have been found to be clinically aggressive, but comparative analysis of clinicopathologic and genomic features is limited. We retrospectively studied cohorts of myeloid neoplasms with classic and nonclassic MECOM rearrangements. Cases with classic rearrangements consisted predominantly of AML, often with inv(3) or t(3;3) as the sole chromosome abnormality, whereas the group of nonclassic rearrangements included a variety of myeloid neoplasms, often with complex karyotype without TP53 mutations and similarly dismal overall survival. Immunohistochemistry revealed Mecom protein overexpression in both groups, but overexpression in cases with nonclassic rearrangements was mediated through a mechanism other than GATA2 distal enhancer involvement typical for classic rearrangement. Our results demonstrated that myeloid neoplasms with nonclassic 3q26.2/MECOM rearrangements encompass a diverse group of diseases with poor clinical outcome, overexpression of Mecom protein as a result of the nonclassic mechanism of MECOM activation.

Relationship between family risk factors and adolescent mental health. / å®¶åº­é£Žé™©å› ç´ ä¸Žé’å°‘å¹´å¿ƒç†å¥åº·ä¹‹é—´çš„å ³ç³».

OBJECTIVES: Family risk factors are crucial to adolescent mental health. Few studies have investigated the complex relationship between family risk factors and adolescent mental health. This study aims to investigate the complex relationship between family cumulative risk (FCR) and adolescent mental health, and to clarify the factors contributing to adolescent mental health problems. METHODS: This study recruited 903 junior high school students and 991 senior high school students in Changsha, Hunan and was conducted through an offline computer-based questionnaire survey using the Middle School Student Mental Health Scale (MSSMHS) and the Family Cumulative Risk Questionnaire (FCRQ) to assess the mental health status and FCR factors, respectively. Statistical analyses were conducted to clarify the demographic factors influencing MSSMHS total and factor scores, and to analyze the relationship between FCRQ and MSSMHS total and factor scores. RESULTS: Females exhibited more mental health problems than males in various MSSMHS factors (all P<0.05); adolescents were prone to different mental health problems at different stages (junior high school first-grade vs. senior high school first-grade); senior high school first-grade students were more likely to experience academic pressure and maladjustment than junior high school first-grade students (P<0.01), and junior high school first-grade students were more likely to exhibit obsessive, paranoia, and hostility symptoms than senior high school first-grade students (all P<0.01); adolescents with low family intimacy and high family conflict reported more symptoms in every dimension of MSSMHS (all P<0.05); adolecents with poor parent-child separation reported higher obsessive-compulsive symptoms, interpersonal sensitivity, anxiety, academic pressure, maladjustment, emotional instability, and unbalanced mind than those with good parent-child separation (all P<0.05). CONCLUSIONS: Female, low family intimacy, high family conflict, and poor parent-child separation are risk factors of adolescent mental health problems. Higher-grade middle school students are prone to exhibit academic pressure and maladjustment, while lower-grade middle school students are prone to exhibit obsessive, paranoia, and hostility symptoms.