Research Progress of Deep-Red to Near-Infrared Electroluminescent Materials Based on Organic Cyclometallated Platinum(II) Complexes.

In recent years, the near-infrared (NIR) light-emitting materials have attracted increasing attention due to the broad application prospects in the fields of military industry, aerospace, lighting, display and wearable devices. As the transition metal complexes, platinum(II) complexes have been shown to emit luminescence efficiently in NIR organic light-emitting diodes because of the unique d8 electron structure. This structure ensures that the platinum(II) complex molecules exhibit a high planarity, variety of excited states, and strong intermolecular interactions. This review summarizes the research progress of deep red to NIR organic light-emitting materials based on platinum(II) complexes in recent years and provides a certain reference for the further design and synthesis of NIR platinum(II) complex luminescent materials with superior performance.

Gender differences in the association between anemia and osteoporosis: findings from a large-scale prospective analysis.

PURPOSE: Osteoporosis (OP) is characterized by a gradual onset and an increased susceptibility to osteoporotic fractures. Previous retrospective studies have suggested that hemoglobin (HGB) levels could be a potential diagnostic marker for OP. However, the relationship between OP and anemia remains uncertain. This prospective study aimed to investigate the association between HGB levels and OP. METHODS: Leveraging data from the UK Biobank, a cohort of 452 778 individuals was analyzed. Employing a modified Cox proportional hazards model that accounted for sociodemographic factors, lifestyle, and health-related factors, we examined the links between incident OP and sex. Moreover, we investigated the impact of OP with or without a pathological fracture. RESULTS: Following a median follow-up period of 5.85 years, 4294 participants were diagnosed with OP. After adjusting for a comprehensive range of pertinent confounders, individuals with anemia exhibited a 2.15-fold higher risk of OP in males and a 1.41-fold higher risk in females. Moreover, each unit increase in HGB concentration corresponded to a 0.83-fold decrease in OP risk for men and a 0.94-fold decrease for women. PERSPECTIVES: Our findings reveal a significant correlation between HGB levels or anemia and OP, with males demonstrating a greater susceptibility compared to females. The risk of OP decreased with higher HGB concentrations in both sexes, although this effect was more pronounced in males. It is recommended to conduct longitudinal studies to investigate the causality of the observed connections and experimental studies to understand the underlying mechanisms.

N6-methyladenosine writer METTL16-mediated alternative splicing and translation control are essential for murine spermatogenesis.

BACKGROUND: The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. RESULTS: We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. CONCLUSIONS: Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

The characteristics of WM in individuals with depressive tendencies: A functional near-infrared spectroscopy (fNIRS) study.

Individuals with depressive tendencies are considered to be at high risk for the onset of depressive disorders. Currently, most research focuses on the impairment of working memory in patients with depression, while there is less attention paid to the WM of individuals with depressive tendencies, and their neural mechanisms underlying it are poorly understood. Therefore, this study focuses on the characteristics and neural mechanisms of WM in individuals with depressive tendencies. This study uses functional near-infrared spectroscopy (fNIRS) to monitor the concentration of Oxy-Hb in the prefrontal cortex and employs the n-back paradigm, designing three levels of load: 0, 1, and 2, to examine the characteristics of WM and its neural mechanisms in individuals with depressive tendencies. Behavioral results show that the accuracy rates of individuals with depressive tendencies is significantly lower than that of healthy individuals, and under the 0-back condition, the reaction time of individuals with depressive tendencies is significantly higher than that of healthy control individuals. Near-infrared results indicate that the activation level in the frontal pole and the dorsal lateral prefrontal cortex of individuals with depressive tendencies is significantly lower than that of healthy control individuals. The ß values of channels 2, 7, and 9 are significantly negatively correlated with the Beck Depression Inventory scores of the participants. The results suggest that the reduced activation of the frontal pole and dorsal lateral prefrontal cortex in individuals with depressive tendencies leads to poorer WM performance compared to healthy control individuals. This is a rare brain evidence of the characteristics of WM in individuals with depressive tendencies, which can provide a deeper understanding of the WM characteristics of individuals with depressive tendencies.

TLR9 promotes monocytic myeloid-derived suppressor cell induction during JEV infection.

Myeloid-derived suppressor cells (MDSCs) are a group of heterologous populations of immature bone marrow cells consisting of progenitor cells of macrophages, dendritic cells and granulocytes. Recent studies have revealed that the accumulation of MDSCs in the mouse spleen plays a pivotal role in suppressing the immune response following JEV infection. However, the mechanisms by which JEV induces MDSCs are poorly understood. Here, it was found that JEV infection induces mitochondrial damage and the release of mitochondrial DNA (mtDNA), which further leads to the activation of TLR9. TLR9 deficiency decreases the M-MDSCs population and their suppressive function both in vitro and in vivo. Moreover, the increase of MHCⅡ expression on antigen-presenting cells and CD28 expression on T cells in TLR9-/- mice was positively correlated with M-MDSCs reduction. Accordingly, the survival rate of TLR9-/- mice dramatically increased after JEV infection. These findings reveal the connections of mitochondrial damage and TLR9 activation to the induction of M-MDSCs during JEV infection.

High PPP4C expression predicts poor prognosis in diffuse large B-cell lymphoma.

The significance of Protein phosphatase 4 catalytic subunit (PPP4C) in diffuse large B-cell lymphoma (DLBCL) prognosis is not well understood. This work aimed to investigate the expression of PPP4C in DLBCL, investigate the correlation between PPP4C expression and clinicopathological parameters, and assess the prognostic significance of PPP4C. The mRNA expression of PPP4C was investigated using data from TCGA and GEO. To further analyze PPP4C expression, immunohistochemistry was performed on tissue microarray samples. Correlation analysis between clinicopathological parameters and PPP4C expression was conducted using Pearson's chi-square test or Fisher's exact test. Univariate and multivariate Cox hazard models were utilized to determine the prognostic significance of clinicopathological features and PPP4C expression. Additionally, survival analysis was performed using Kaplan-Meier survival curves. In both TCGA and GEO datasets, we identified higher mRNA levels of PPP4C in tumor tissues compared to normal tissues. Upon analysis of various clinicopathological features of DLBCL, we observed a correlation between high PPP4C expression and ECOG score (P = 0.003). Furthermore, according to a Kaplan-Meier survival analysis, patients with DLBCL who exhibit high levels of PPP4C had worse overall survival (P = 0.001) and progression-free survival (P = 0.002). PPP4C was shown to be an independent predictive factor for OS and PFS in DLBCL by univariate and multivariate analysis (P = 0.011 and P = 0.040). This study's findings indicate that high expression of PPP4C is linked to a poor prognosis for DLBCL and may function as an independent prognostic factors.

Squalene-epoxidase-catalyzed 24(S),25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.

The importance of trained immunity in antitumor immunity has been increasingly recognized, but the underlying metabolic regulation mechanisms remain incompletely understood. In this study, we find that squalene epoxidase (SQLE), a key enzyme in cholesterol synthesis, is required for ß-glucan-induced trained immunity in macrophages and ensuing antitumor activity. Unexpectedly, the shunt pathway, but not the classical cholesterol synthesis pathway, catalyzed by SQLE, is required for trained immunity induction. Specifically, 24(S),25-epoxycholesterol (24(S),25-EC), the shunt pathway metabolite, activates liver X receptor and increases chromatin accessibility to evoke innate immune memory. Meanwhile, SQLE-induced reactive oxygen species accumulation stabilizes hypoxia-inducible factor 1α protein for metabolic switching into glycolysis. Hence, our findings identify 24(S),25-EC as a key metabolite for trained immunity and provide important insights into how SQLE regulates trained-immunity-mediated antitumor activity.

Inherited KDM6AA649T facilitates tumor-immune escape and exacerbates colorectal signet-ring cell carcinoma outcomes.

Childhood onset of colorectal signet-ring cell carcinoma (CR-SRCC) is extremely rare and featured as highly malignant with poor prognosis. Here we reported a CR-SRCC case of 11-year-old boy with a novel inherited X-linked KDM6AA694T mutation. The H3K27me3 demethylase KDM6A was frequently mutated in varieties of tumors and acts as a tumor suppressor. In vivo H3K27me3 demethylation assay demonstrated that KDM6AA694T had dampened H3K27me3 demethylase activity. Overexpression of KDM6AA694T in SRCC cell line KATO3 promoted cell proliferation, invasion and migration, which were further confirmed in vivo by constructing orthotopic tumor growth and lung metastasis model. Besides, expression of KDM6AA694T in immune cells suppresses inflammatory macrophage response and effector T cell response. In conclusion, we characterized a novel inherited KDM6AA694T mutant from a childhood-onset SRCC case and demonstrated that the mutant with impaired H3K27me3 demethylase activity could potentiate tumor malignancy and suppress antitumor immunity.

BAG5 regulates HSPA8-mediated protein folding required for sperm head-tail coupling apparatus assembly.

Teratozoospermia is a significant cause of male infertility, but the pathogenic mechanism of acephalic spermatozoa syndrome (ASS), one of the most severe teratozoospermia, remains elusive. We previously reported Spermatogenesis Associated 6 (SPATA6) as the component of the sperm head-tail coupling apparatus (HTCA) required for normal assembly of the sperm head-tail conjunction, but the underlying molecular mechanism has not been explored. Here, we find that the co-chaperone protein BAG5, expressed in step 9-16 spermatids, is essential for sperm HTCA assembly. BAG5-deficient male mice show abnormal assembly of HTCA, leading to ASS and male infertility, phenocopying SPATA6-deficient mice. In vivo and in vitro experiments demonstrate that SPATA6, cargo transport-related myosin proteins (MYO5A and MYL6) and dynein proteins (DYNLT1, DCTN1, and DNAL1) are misfolded upon BAG5 depletion. Mechanistically, we find that BAG5 forms a complex with HSPA8 and promotes the folding of SPATA6 by enhancing HSPA8's affinity for substrate proteins. Collectively, our findings reveal a novel protein-regulated network in sperm formation in which BAG5 governs the assembly of the HTCA by activating the protein-folding function of HSPA8.

The effect of metabolic syndrome on prognosis of diffuse large B-cell lymphoma.

PURPOSE: Metabolic syndrome (MetS), characterized by insulin resistance, is closely associated with the prognosis of various cancer types, but has not been reported in diffuse large B-cell lymphoma (DLBCL). The aim of this study is to examine how other clinicopathological variables and the MetS influence the prognosis of DLBCL. METHODS: Clinical and pathological data were collected from 319 patients with DLBCL who were admitted to our hospital between January 2012 and December 2020. The data accessible with SPSS 27.0 enables the utilization of various statistical methods for clinical data analysis, including independent sample t test and univariate and multivariate COX regression. RESULTS: The presence of MetS was linked to both overall survival (OS) and progression-free survival (PFS), in addition to other clinicopathological characteristics as age, IPI score, rituximab usage, and Ki-67 expression level. This link with OS and PFS indicated a poor prognosis, as shown by survival analysis. Subsequent univariate analysis identified IPI score, Ki-67 expression level, tumor staging, rituximab usage, lactate dehydrogenase expression level, and the presence or absence of MetS as factors linked with OS and PFS. Furthermore, multivariate Cox regression analysis confirmed the independent risk factor status of IPI score, Ki-67 expression level, rituximab usage, and the presence of MetS in evaluating the prognosis of patients with DLBCL. CONCLUSION: This study's findings indicate that patients with pre-treatment MetS had a poor prognosis, with relatively shorter OS and PFS compared to those without pre-treatment MetS. Furthermore, the presence of MetS, IPI score, Ki-67 expression level, and rituximab usage were identified as independent risk factors significantly affecting the prognosis of DLBCL.

Recent advances of organic emitters in deep-red light-emitting electrochemical cells.

Light-emitting electrochemical cells (LECs) are kind of easily fabricated and low-cost light-emitting devices that can efficiently convert electric power to light energy. Compared with blue and green LECs, the performance of deep-red LECs is limited by the high non-radiative rate of emitters in long-wavelength region. While various organic emitters with deep-red emission have been developed to construct high-performance LECs, including polymers, metal complexes, and organic luminous molecules (OLMs), but this is seldom summarized. Therefore, we overview the recent advances of organic emitters with emission at the deep-red region for LECs, and specifically highlight the molecular design approach and electrochemiluminescence performance. We hope that this review can act as a reference for further research in designing high-performance deep-red LECs.

A magnetic solid phase extraction microfluidic chip coupled with gas chromatography-mass spectrometry for the determination of polycyclic aromatic hydrocarbons in aqueous samples.

In this paper, we designed and manufactured a reliable magnetic solid phase extraction (MSPE) microfluidic chip for determination of polycyclic aromatic hydrocarbons (PAHs) in water combined with gas chromatography-mass spectrometry. Sample loading, washing and elution are implemented with microinjection pump and integrated on a single chip, which reduced manual operation. Magnets were used to fix octadecyl/phenyl bifunctional Fe3O4@SiO2 extractant to avoid the design of weir structure in extraction chamber. The whole microfluidic chip was simple and low cost. Based on the microfluidic chip extraction platform, the on-chip MSPE method for the determination of PAHs was optimized and established. The results showed that this method required only 2 mL of sample, 2 mg of extractant, and 50 µL of elution organic solvent for whole on-chip MSPE process, which was environmentally friendly and consistent with green chemistry. Method verification results were displayed which the linear range of five PAHs was between 1-100 ng/mL with good linearity (R2≥ 0.9985), and the detection limits (S/N = 3) were 0.08-0.26 ng/mL. The RSDs of intra-day precision (n=6) and inter-day precision (n=9) for PAHs were less than 6.1 % and 7.2 %, respectively. Enrichment factors were determined to be 31.3-37.7. The recoveries of river water, tap water, bottle water, waste water and urine at three spiked levels were in the range of 89.9% to 113.7% and the matrix effect values were between 83.8% to 109.6%. The extraction platform has the advantages of accurate analysis, simple design and cost-effective, which is conducive to the widespread use of microfluidic chips.

A general dual-pathway network for EEG denoising.

Introduction: Scalp electroencephalogram (EEG) analysis and interpretation are crucial for tracking and analyzing brain activity. The collected scalp EEG signals, however, are weak and frequently tainted with various sorts of artifacts. The models based on deep learning provide comparable performance with that of traditional techniques. However, current deep learning networks applied to scalp EEG noise reduction are large in scale and suffer from overfitting. Methods: Here, we propose a dual-pathway autoencoder modeling framework named DPAE for scalp EEG signal denoising and demonstrate the superiority of the model on multi-layer perceptron (MLP), convolutional neural network (CNN) and recurrent neural network (RNN), respectively. We validate the denoising performance on benchmark scalp EEG artifact datasets. Results: The experimental results show that our model architecture not only significantly reduces the computational effort but also outperforms existing deep learning denoising algorithms in root relative mean square error (RRMSE)metrics, both in the time and frequency domains. Discussion: The DPAE architecture does not require a priori knowledge of the noise distribution nor is it limited by the network layer structure, which is a general network model oriented toward blind source separation.

Does global positioning system-based navigation dependency make your sense of direction poor? A psychological assessment and eye-tracking study.

Background: Global positioning system (GPS)-based navigation apps are very useful in our lives. However, whether and how the usage of these apps affects spatial cognition and the sense of direction is still unclear. Methods: A total of 108 individuals were recruited and completed the GPS dependence, internet gaming behavior, and impulsivity test using scales. The eye-tracking-based general mental rotation (MR) task and target finding (TF; require individuals to find a target specified in a 3D street map in a rotated version of top 2D view map) task were used to assess their spatial cognition and the sense of direction. The correlation was used to relate GPS navigation usage, spatial cognition ability, and impulsivity. Subgroup analyses stratifying by gaming hours of individuals (< 2 h or ≥ 2 h) or maps (countryside or city) in TF task were performed. The moderating and mediating effect analyses were conducted to verify these relationships. Results: The GPS dependency score was nominal positively correlated with fixations in the TF task in the entire cohort (r = 0.202, unadjusted p = 0.036); it was significant in city (r = 0.254, p = 0.008) and gaming time of < 2 h (r = 0.459, p = 0.001) subgroups. The high-score (upper 30%) group of GPS dependency had more fixations on the original target building in the training area and indicative building in the test area than the low-score (lower 30%) group. GPS dependency was not associated with the correct rate and reaction time in the TF task or any of the indicators in the MR task (p > 0.05). The GPS dependency mediated the indirect effect of impulsivity on the fixations on TF. The internet gaming time moderated the association between GPS dependency and fixations on TF. Conclusion: The dependency on GPS-based navigation apps was associated with impaired spatial cognition but may not significantly affect the sense of direction.

Abnormal psychological performance as potential marker for high risk of internet gaming disorder: An eye-tracking study and support vector machine analysis.

Individuals with high risk of internet gaming disorder (HIGD) showed abnormal psychological performances in response inhibition, impulse control, and emotion regulation, and are considered the high-risk stage of internet gaming disorder (IGD). The identification of this population mainly relies on clinical scales, which are less accurate. This study aimed to explore whether these performances have highly accurate for discriminating HIGD from low-risk ones. Eye tracking based anti-saccade task, Barratt impulsiveness scale (BIS), and Wong and Law emotional intelligence scale (WLEIS) were used to evaluate psychological performances in 57 individuals with HIGD and 52 matched low risk of internet gaming disorder (LIGD). HIGD group showed significantly increased BIS total (t = -2.875, p = 0.005), attention (t = -2.139, p = 0.035), motor (t = -2.017, p = 0.046), and non-planning (t = -2.171, p = 0.032) scores, but significantly decreased WLEIS emotion regulation score (t = 2.636, p = 0.010) and correct rate of eye tracking anti-saccade task (t = 2.294, p = 0.024) compared with LIGD group. BIS total score was negatively correlated with the WLEIS total (r = -0.473, p < 0.001) and WLEIS emotion regulation (r = -0.366, p < 0.001) scores. A combination of the WLEIS emotion regulation score and the correct rate of anti-saccade task could discriminate HIGD from LIGD with 91.23% sensitivity, 82.69% specificity, and 87.16% accuracy. Participants with higher gaming hours daily were 40 times more likely to be high risk than their counterparts (p < 0.001). Hence, psychological performances were worse in HIGD. A combination of abnormal emotion regulation and response inhibition might be a potential marker to identify HIGD individuals.

Corrigendum: brain microvascular endothelial cell-derived HMGB1 facilitates monocyte adhesion and transmigration to promote JEV neuroinvasion.

[This corrects the article DOI: 10.3389/fcimb.2021.701820.].

Brown-fat-mediated tumour suppression by cold-altered global metabolism.

Glucose uptake is essential for cancer glycolysis and is involved in non-shivering thermogenesis of adipose tissues1-6. Most cancers use glycolysis to harness energy for their infinite growth, invasion and metastasis2,7,8. Activation of thermogenic metabolism in brown adipose tissue (BAT) by cold and drugs instigates blood glucose uptake in adipocytes4,5,9. However, the functional effects of the global metabolic changes associated with BAT activation on tumour growth are unclear. Here we show that exposure of tumour-bearing mice to cold conditions markedly inhibits the growth of various types of solid tumours, including clinically untreatable cancers such as pancreatic cancers. Mechanistically, cold-induced BAT activation substantially decreases blood glucose and impedes the glycolysis-based metabolism in cancer cells. The removal of BAT and feeding on a high-glucose diet under cold exposure restore tumour growth, and genetic deletion of Ucp1-the key mediator for BAT-thermogenesis-ablates the cold-triggered anticancer effect. In a pilot human study, mild cold exposure activates a substantial amount of BAT in both healthy humans and a patient with cancer with mitigated glucose uptake in the tumour tissue. These findings provide a previously undescribed concept and paradigm for cancer therapy that uses a simple and effective approach. We anticipate that cold exposure and activation of BAT through any other approach, such as drugs and devices either alone or in combination with other anticancer therapeutics, will provide a general approach for the effective treatment of various cancers.

Hierarchical Accumulation of Histone Variant H2A.Z Regulates Transcriptional States and Histone Modifications in Early Mammalian Embryos.

Early embryos undergo extensive epigenetic reprogramming to achieve gamete-to-embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. However, how does H2A.Z regulate gene expression and histone modifications during preimplantation development remains unrevealed. Here, by using ultra-low-input native chromatin immunoprecipitation and sequencing, the genome-wide distribution of H2A.Z is delineated in mouse oocytes and early embryos. These landscapes indicate that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). Remarkably, H2A.Z exhibits hierarchical accumulation as different peak types at promoters: promoters with double H2A.Z peaks are colocalized with H3K4me3 and indicate transcriptional activation; promoters with a single H2A.Z peak are more likely to occupy bivalent marks (H3K4me3+H3K27me3) and indicate development gene suppression; promoters with no H2A.Z accumulation exhibit persisting gene silencing in early embryos. Moreover, H2A.Z depletion changes the enrichment of histone modifications and RNA polymerase II binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Furthermore, similar transcription and accumulation patterns between mouse and porcine embryos indicate that a dual role of H2A.Z in regulating the epigenome required for proper gene expression is conserved during mammalian preimplantation development.

Mutations in PpAGO3 Lead to Enhanced Virulence of Phytophthora parasitica by Activation of 25-26 nt sRNA-Associated Effector Genes.

Oomycetes represent a unique group of plant pathogens that are destructive to a wide range of crops and natural ecosystems. Phytophthora species possess active small RNA (sRNA) silencing pathways, but little is known about the biological roles of sRNAs and associated factors in pathogenicity. Here we show that an AGO gene, PpAGO3, plays a major role in the regulation of effector genes hence the pathogenicity of Phytophthora parasitica. PpAGO3 was unique among five predicted AGO genes in P. parasitica, showing strong mycelium stage-specific expression. Using the CRISPR-Cas9 technology, we generated PpAGO3ΔRGG1-3 mutants that carried a deletion of 1, 2, or 3 copies of the N-terminal RGG motif (QRGGYD) but failed to obtain complete knockout mutants, which suggests its vital role in P. parasitica. These mutants showed increased pathogenicity on both Nicotiana benthamiana and Arabidopsis thaliana plants. Transcriptome and sRNA sequencing of PpAGO3ΔRGG1 and PpAGO3ΔRGG3 showed that these mutants were differentially accumulated with 25-26 nt sRNAs associated with 70 predicted cytoplasmic effector genes compared to the wild-type, of which 13 exhibited inverse correlation between gene expression and 25-26 nt sRNA accumulation. Transient overexpression of the upregulated RXLR effector genes, PPTG_01869 and PPTG_15425 identified in the mutants PpAGO3ΔRGG1 and PpAGO3ΔRGG3 , strongly enhanced N. benthamiana susceptibility to P. parasitica. Our results suggest that PpAGO3 functions together with 25-26 nt sRNAs to confer dynamic expression regulation of effector genes in P. parasitica, thereby contributing to infection and pathogenicity of the pathogen.