A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Acetylation of aldehyde dehydrogenase ALDH1L2 regulates cellular redox balance and the chemosensitivity of colorectal cancer to 5-fluorouracil.

Folate-mediated one-carbon metabolism (FOCM) is crucial in sustaining rapid proliferation and survival of cancer cells. The folate cycle depends on a series of key cellular enzymes, including aldehyde dehydrogenase 1 family member L2 (ALDH1L2) that is usually overexpressed in cancer cells, but the regulatory mechanism of ALDH1L2 remains undefined. In this study, we observed the significant overexpression of ALDH1L2 in colorectal cancer (CRC) tissues, which is associated with poor prognosis. Mechanistically, we identified that the acetylation of ALDH1L2 at the K70 site is an important regulatory mechanism inhibiting the enzymatic activity of ALDH1L2 and disturbing cellular redox balance. Moreover, we revealed that sirtuins 3 (SIRT3) directly binds and deacetylates ALDH1L2 to increase its activity. Interestingly, the chemotherapeutic agent 5-fluorouracil (5-Fu) inhibits the expression of SIRT3 and increases the acetylation levels of ALDH1L2 in colorectal cancer cells. 5-Fu-induced ALDH1L2 acetylation sufficiently inhibits its enzymatic activity and the production of NADPH and GSH, thereby leading to oxidative stress-induced apoptosis and suppressing tumor growth in mice. Furthermore, the K70Q mutant of ALDH1L2 sensitizes cancer cells to 5-Fu both in vitro and in vivo through perturbing cellular redox and serine metabolism. Our findings reveal an unknown 5-Fu-SIRT3-ALDH1L2 axis regulating redox homeostasis, and suggest that targeting ALDH1L2 is a promising therapeutic strategy to sensitize tumor cells to chemotherapeutic agents.

LINC01852 inhibits the tumorigenesis and chemoresistance in colorectal cancer by suppressing SRSF5-mediated alternative splicing of PKM.

BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. METHODS: In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance. LINC01852 expression was evaluated in multiple CRC cohorts using quantitative reverse transcription PCR. We conducted in vitro and in vivo functional experiments using cell culture and mouse models. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of LINC01852 in CRC. RESULTS: Our findings revealed that a lncRNA with tumor-inhibiting properties, LINC01852, was downregulated in CRC and inhibited cell proliferation and chemoresistance both in vitro and in vivo. Further mechanistic investigations revealed that LINC01852 increases TRIM72-mediated ubiquitination and degradation of SRSF5, inhibiting SRSF5-mediated alternative splicing of PKM and thereby decreasing the production of PKM2. Overexpression of LINC01852 induces a metabolic switch from aerobic glycolysis to oxidative phosphorylation, which attenuates the chemoresistance of CRC cells by inhibiting PKM2-mediated glycolysis. CONCLUSIONS: Our results demonstrate that LINC01852 plays an important role in repressing CRC malignancy and chemoresistance by regulating SRSF5-mediated alternative splicing of PKM, and that targeting the LINC01852/TRIM72/SRSF5/PKM2 signaling axis may represent a potential therapeutic strategy for CRC.

exoRBase 2.0: an atlas of mRNA, lncRNA and circRNA in extracellular vesicles from human biofluids.

Extracellular vesicles (EVs) are small membranous vesicles that contain an abundant cargo of different RNA species with specialized functions and clinical implications. Here, we introduce an updated online database (http://www.exoRBase.org), exoRBase 2.0, which is a repository of EV long RNAs (termed exLRs) derived from RNA-seq data analyses of diverse human body fluids. In exoRBase 2.0, the number of exLRs has increased to 19 643 messenger RNAs (mRNAs), 15 645 long non-coding RNAs (lncRNAs) and 79 084 circular RNAs (circRNAs) obtained from ∼1000 human blood, urine, cerebrospinal fluid (CSF) and bile samples. Importantly, exoRBase 2.0 not only integrates and compares exLR expression profiles but also visualizes the pathway-level functional changes and the heterogeneity of origins of circulating EVs in the context of different physiological and pathological conditions. Our database provides an attractive platform for the identification of novel exLR signatures from human biofluids that will aid in the discovery of new circulating biomarkers to improve disease diagnosis and therapy.

The association between prenatal bisphenol F exposure and infant neurodevelopment: The mediating role of placental estradiol.

BACKGROUND: There are limited population studies on the neurodevelopmental effects of bisphenol F (BPF), a substitute for bisphenol A. Furthermore, the role of placental estradiol as a potential mediator linking these two factors remains unclear. OBJECTIVE: To examine the association between maternal prenatal BPF exposure and infant neurodevelopment in a prospective cohort study and to explore the mediating effects of placental estradiol between BPF exposure and neurodevelopment in a nested case-control study. METHODS: The prospective cohort study included 1077 mother-neonate pairs from the Wuhu city cohort study in China. Maternal BPF was determined using the liquid/liquid extraction and Ultra-performance liquid chromatography tandem mass spectrometry method. Children's neurodevelopment was assessed at ages 3, 6, and 12 months using Ages and Stages Questionnaires. The nested case-control study included 150 neurodevelopmental delay cases and 150 healthy controls. Placental estradiol levels were measured using enzyme-linked immunosorbent assay kits. Generalized estimating equation models and robust Poisson regression models were used to examine the associations between BPF exposure and children's neurodevelopment. In the nested case-control study, causal mediation analysis was conducted to assess the role of placental estradiol as a mediator in multivariate models. RESULTS: In the prospective cohort study, the pregnancy-average BPF concentration was positively associated with developmental delays in gross-motor, fine-motor, and problem-solving ( ORtotal ASQ: 1.14(1.05, 1.25), ORgross-motor: 1.22(1.10, 1.36), ORfine-motor: 1.19(1.07, 1.31), ORproblem-solving: 1.11(1.01, 1.23)). After sex-stratified analyses, pregnancy-average BPF concentration was associated with an increased risk of neurodevelopmental delays in the gross-motor (ORgross-motor:1.30(1.12, 1.51)) and fine-motor (ORfine-motor: 1.22(1.06, 1.40)) domains in boys. In the nested case-control study, placental estradiol mediated 16.6% (95%CI: 4.4%, 35.0%) of the effects of prenatal BPF exposure on developmental delay. CONCLUSIONS: Our study supports an inverse relationship between prenatal BPF exposure and child neurodevelopment in infancy, particularly in boys. Decreased placental estradiol may be an underlying biological pathway linking prenatal BPF exposure to neurodevelopmental delay in offspring.

The Photocatalytic Performance of P, Cl Doped Carboxylated Multiwalled Carbon Nanotube Modified Graphitic Carbon Nitride.

Graphitized carbonitride (g-C3N4) is widely used in CO2 reduction, hydrogen production, and degradation of toxic chemical dyes and antibiotics. It is a kind of photocatalytic material with excellent performance, and it has the advantages of being safe and nontoxic, having a suitable band gap (2.7 eV), and having a simple preparation and high stability, but because of its fast optical recombination speed and low visible light overutilization, the multifunctional application of g-C3N4 is seriously hindered. Compared with pure g-C3N4, MWCNTs/g-C3N4 have a red-shift in the visible range and a strong absorption in the visible region. Melamine and carboxylated multiwalled carbon nanotubes were used as raw materials to successfully prepare CMWCNT modified g-C3N4 doped with P, Cl by a high temperature calcination method. The effect of the addition amount of P, Cl on the photocatalytic performance of modified g-C3N4 was studied. The experimental results show that the multiwalled carbon nanotubes can accelerate the electron migration, and the doping of P, Cl elements can change the energy band structure of g-C3N4 and reduce the band gap. Through fluorescence analysis and photocurrent analysis, it is known that the incorporation of P, Cl reduces the recombination efficiency of photogenerated electron-hole pairs. In order to explore the application in the degradation of chemical dyes, the photocatalytic degradation efficiency of RhB under visible light was studied. The photocatalytic performance of the samples was evaluated by photodecomposition of aquatic hydrogen. The results showed that when the amount of ammonium dihydrogen phosphate was 10 wt %, the photocatalytic degradation efficiency was the highest, which was 21.13 times higher than that of g-C3N4.

Optimal shapes of disk assembly in saturated random packings.

Particle morphology is one of the most significant factors influencing the packing structures of granular materials. With certain targeted properties or optimization criteria, inverse packing problems have drawn extensive attention in terms of their adaptability to many material design tasks. An important question hard to answer is which particle shape, especially within given shape families, forms the densest (loosest) random packing? In this paper, we address this issue for the disk assembly model in two dimensions with an infinite variety of shapes, which are simulated in the random sequential adsorption process to suppress crystallization. Via a unique shape representation method, particle shapes are transformed into genotype sequences in the continuous shape space where we utilize the genetic algorithm as an efficient shape optimizer. Specifically, we consider three representative species of disk assembly, i.e., congruent tangent disks, incongruent tangent disks, and congruent overlapping disks, and carry out shape optimization on their packing densities in the saturated random state. We numerically search optimal shapes in the three species with a variable number of constituent disks which yield the maximal and minimal packing densities. We obtain an isosceles circulo-triangle and an unclosed ring for the maximal and minimal packing density in saturated random packings, respectively. The perfect sno-cone and isosceles circulo-triangle are also specifically investigated which give remarkably high packing densities of around 0.6, much denser than those of ellipses. This study is beneficial for guiding the design of particle shapes as well as the inverse design of granular materials.

High-Efficiency Ce3+ Activated Orthorhombic Lanthanide Silicate Blue Phosphors for Plant Growth Lighting.

Plant growth can be controlled and freed from natural environmental interference through indoor plant cultivation. Artificial light sources with better quality are required to promote indoor plant growth. In this study, we used a simple high-temperature solid-state reaction to synthesize high-efficiency Ce3+-activated NaGdSiO4 (NGSO) phosphors. X-ray diffraction and Rietveld refinement were performed to determine the detailed crystal structure of the NGSO:Ce3+ phosphors. The morphology of NGSO:Ce3+ and the elemental state of Ce3+ were measured and analyzed. Under near-ultraviolet (n-UV) light excitation, the Ce3+-activated NGSO phosphors exhibit a broad emission band from 375 to 500 nm, and their emission peaks are at approximately 401 nm. This asymmetrical blue emission band is caused by the spin-allowed 5d → 4f transition of Ce3+ and overlaps well with the blue absorption region of carotenoids and chlorophyll. The temperature-dependent luminescence spectra were utilized to assess the thermal stability of NGSO:Ce3+. The external quantum efficiency (EQE) was measured to be 60.91%, and the internal quantum efficiency (IQE) was measured to be 73.39%. A blue LED device assembled from the NGSO:Ce3+ phosphor has demonstrated the application potential in accelerating plant growth.

Gamma-Aminobutyric Acid Type A Receptor Subunit Pi is a potential chemoresistance regulator in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the cancers with high morbidity and mortality worldwide. Chemotherapy is commonly used for metastatic or more advanced CRC. The mechanism of CRC chemoresistance is still under active investigation. Therefore, we identify and validate differentially expressed genes (DEGs) between oxaliplatin/5-FU resistant and sensitive CRC cells. METHODS AND RESULTS: Three datasets of colorectal cancer patients (GSE28691, GSE81006, and GSE77932) from the Gene Expression Omnibus (GEO) database were analyzed and volcano plots for DEGs were generated using the GEO2R tool. The intersection of three GEO datasets showed that GABRP was significantly upregulated in chemo-resistant CRC cells or patients with an adjusted p-value less than 0.01. The potential protein-protein interaction (PPI) network with GABRP was analyzed by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) website. The PPI network predicted ANKRD66, CLINT1, HAP1, PLCL1, GABARPAP, GABARAPL1, NSF, GABARAPL2, TRAK2, and CLIC3 had a high likelihood to interact with GABRP. Especially, GABARAP, GABARAPL1, ANKRD66, CLINT1, and CLIC3 were enriched as the most possibly associated proteins with GABRP among the networks. GABRP was significantly more expressed in both oxaliplatin/5-FU resistant CRC cells than in those counterpart sensitive CRC cells using quantitative PCR (qPCR) analysis. Consistently, TCGA, Oncomine, and Human Protein Atlas (HPA) databases confirmed that higher expression of GABRP was robustly found in CRC patients than those in other various cancer types or normal colon tissues. CONCLUSION: We identify GABRP as a promising drug target to mediate oxaliplatin or 5-FU resistance in CRC. It provided the theoretical basis and potential clinical value for CRC patients.

Perceived rather than objective weight status is associated with suicidal behaviors among Chinese adolescents: a school-based study.

BACKGROUND: We aimed to explore the relationship between body mass index (BMI) and body weight perception (BWP) with suicidal behaviors among mainland Chinese adolescents. METHODS: A nationally representative sample (N = 10 110) of Chinese adolescents was assessed in this study. Suicidal behaviors (ideation, plan and attempt) were evaluated by four self-reported questions. Generalized linear mixed model was used to estimate the adjusted odds ratios (ORs) for the association between BWP/BMI with suicidal behaviors. RESULTS: The prevalence of suicidal ideation, suicidal plan and suicidal attempt was 12, 5 and 2.1%, respectively. After adjusting potential covariates, perceiving oneself as obese was significantly associated with increased risks of suicidal ideation (OR: 2.4, 95% confidence intervals, CI: 1.6-4.0, P = 0.001), suicidal plan (OR: 3.1, 95% CI: 1.5-6.3, P = 0.002) and suicidal attempt (OR: 3.7, 95% CI: 1.5-9.1, P = 0.001) compared with perceiving as normal weight among male adolescents; the effect attenuated to null among female adolescents. Perceiving oneself as underweight and overweight both exhibited significant adverse effect on suicidal behaviors (only suicidal ideation and suicidal plan) compared with perceiving oneself as normal weight among male adolescents, but not among female adolescents. The actual measured BMI was not significantly associated with suicidal behaviors among neither gender. CONCLUSIONS: Self-perception of their body image rather than actual measured weight may have a gender-specific adverse effect on suicidal behaviors among Chinese adolescents.

RJunBase: a database of RNA splice junctions in human normal and cancerous tissues.

Splicing is an essential step of RNA processing for multi-exon genes, in which introns are removed from a precursor RNA, thereby producing mature RNAs containing splice junctions. Here, we develope the RJunBase (www.RJunBase.org), a web-accessible database of three types of RNA splice junctions (linear, back-splice, and fusion junctions) that are derived from RNA-seq data of non-cancerous and cancerous tissues. The RJunBase aims to integrate and characterize all RNA splice junctions of both healthy or pathological human cells and tissues. This new database facilitates the visualization of the gene-level splicing pattern and the junction-level expression profile, as well as the demonstration of unannotated and tumor-specific junctions. The first release of RJunBase contains 682 017 linear junctions, 225 949 back-splice junctions and 34 733 fusion junctions across 18 084 non-cancerous and 11 540 cancerous samples. RJunBase can aid researchers in discovering new splicing-associated targets and provide insights into the identification and assessment of potential neoepitopes for cancer treatment.

Assessing resource allocation based on workload: a data envelopment analysis study on clinical departments in a class a tertiary public hospital in China.

OBJECTIVE: Today, the development mode of public hospitals in China is turning from expansion to efficiency, and the management mode is turning from extensive to refined. This study aims to evaluate the efficiency of clinical departments in a Chinese class A tertiary public hospital (Hospital M) to analyze the allocation of hospital resources among these departments providing a reference for the hospital management. METHODS: The hospitalization data of inpatients from 32 clinical departments of Hospital M in 2021 are extracted from the hospital information system (HIS), and a dataset containing 38,147 inpatients is got using stratified sampling. Considering the non-homogeneity of clinical departments, the 38,147 patients are clustered using the K-means algorithm based on workload-related data labels including inpatient days, intensive care workload index, nursing workload index, and operation workload index, so that the medical resource consumption of inpatients from non-homogeneous clinical departments can be transformed into the homogeneous workload of medical staff. Taking the numbers of doctors, nurses, and beds as input indicators, and the numbers of inpatients assigned to certain clusters as output indicators, an input-oriented BCC model is built named the workload-based DEA model. Meanwhile, a control DEA model with the number of inpatients and medical revenue as output indicators is built, and the outputs of the two models are compared and analyzed. RESULTS: Clustering of 38,147 patients into 3 categories is of better interpretability. 14 departments reach DEA efficient in the workload-based DEA model, 10 reach DEA efficient in the control DEA model, and 8 reach DEA efficient in both models. The workload-based DEA model gives a relatively rational judge on the increase of income brought by scale expansion, and evaluates some special departments like Critical Care Medicine Dept., Geriatrics Dept. and Rehabilitation Medicine Dept. more properly, which better adapts to the functional orientation of public hospitals in China. CONCLUSION: The design of evaluating the efficiency of non-homogeneous clinical departments with the workload as output proposed in this study is feasible, and provides a new idea to quantify professional medical human resources, which is of practical significance for public hospitals to optimize the layout of resources, to provide real-time guidance on manpower grouping strategies, and to estimate the expected output reasonably.

Eu3+ -activated red phosphor Ca3 YAl3 B4 O15 with low thermal quenching behaviour.

This paper reports a sequence of a Ca3 YAl3 B4 O15 :xEu3+ red phosphor prepared using a high-temperature solid-state reaction. At the excitation of 396 nm, the samples emitted intense red emission centred at ~623 nm, which could be attributed to the 5 D0 →7 F2 transition of the Eu3+ ion. The results showed that the optimum Eu3+ doping concentration of Ca3 YAl3 B4 O15 :Eu3+ phosphor was x = 80 mol%, and the concentration quenching mechanism of Ca3 YAl3 B4 O15 :Eu3+ red phosphor belonged to the exchange coupling between Eu3+ ions. The Commission Internationale de l'éclairage (CIE) coordinates and colour purity of Ca3 Y0.2 Al3 B4 O15 :0.8Eu3+ were calculated as (0.6375, 0.3476) and 95.5%, respectively. Moreover, the red emission of the obtained phosphor Ca3 YAl3 B4 O15 :0.8Eu3+ exhibited a low thermal quenching behaviour with an intensity retention rate of 92.85% at 150°C. The above results manifest that the Eu3+ -activated Ca3 YAl3 B4 O15 phosphor is predicted to be a promising red luminescent component for white light-emitting diodes.

CT imaging-based radiomics signatures improve prognosis prediction in postoperative colorectal cancer.

OBJECTIVE: To investigate the use of non-contrast-enhanced (NCE) and contrast-enhanced (CE) CT radiomics signatures (Rad-scores) as prognostic factors to help improve the prediction of the overall survival (OS) of postoperative colorectal cancer (CRC) patients. METHODS: A retrospective analysis was performed on 65 CRC patients who underwent surgical resection in our hospital as the training set, and 19 patient images retrieved from The Cancer Imaging Archive (TCIA) as the external validation set. In training, radiomics features were extracted from the preoperative NCE/CE-CT, then selected through 5-fold cross validation LASSO Cox method and used to construct Rad-scores. Models derived from Rad-scores and clinical factors were constructed and compared. Kaplan-Meier analyses were also used to compare the survival probability between the high- and low-risk Rad-score groups. Finally, a nomogram was developed to predict the OS. RESULTS: In training, a clinical model achieved a C-index of 0.796 (95% CI: 0.722-0.870), while clinical and two Rad-scores combined model performed the best, achieving a C-index of 0.821 (95% CI: 0.743-0.899). Furthermore, the models with the CE-CT Rad-score yielded slightly better performance than that of NCE-CT in training. For the combined model with CE-CT Rad-scores, a C-index of 0.818 (95% CI: 0.742-0.894) and 0.774 (95% CI: 0.556-0.992) were achieved in both the training and validation sets. Kaplan-Meier analysis demonstrated a significant difference in survival probability between the high- and low-risk groups. Finally, the areas under the receiver operating characteristics (ROC) curves for the model were 0.904, 0.777, and 0.843 for 1, 3, and 5-year survival, respectively. CONCLUSION: NCE-CT or CE-CT radiomics and clinical combined models can predict the OS for CRC patients, and both Rad-scores are recommended to be included when available.

Long noncoding RNA DLGAP1-AS2 promotes tumorigenesis and metastasis by regulating the Trim21/ELOA/LHPP axis in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have driven research focused on their effects as oncogenes or tumor suppressors involved in carcinogenesis. However, the functions and mechanisms of most lncRNAs in colorectal cancer (CRC) remain unclear. METHODS: The expression of DLGAP1-AS2 was assessed by quantitative RT-PCR in multiple CRC cohorts. The impacts of DLGAP1-AS2 on CRC growth and metastasis were evaluated by a series of in vitro and in vivo assays. Furthermore, the underlying mechanism of DLGAP1-AS2 in CRC was revealed by RNA pull down, RNA immunoprecipitation, RNA sequencing, luciferase assays, chromatin immunoprecipitation, and rescue experiments. RESULTS: We discovered that DLGAP1-AS2 promoted CRC tumorigenesis and metastasis by physically interacting with Elongin A (ELOA) and inhibiting its protein stability by promoting tripartite motif containing 21 (Trim21)-mediated ubiquitination modification and degradation of ELOA. In particular, we revealed that DLGAP1-AS2 decreases phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) expression by inhibiting ELOA-mediated transcriptional activating of LHPP and thus blocking LHPP-dependent suppression of the AKT signaling pathway. In addition, we also demonstrated that DLGAP1-AS2 was bound and stabilized by cleavage and polyadenylation specificity factor (CPSF2) and cleavage stimulation factor (CSTF3). CONCLUSIONS: The discovery of DLGAP1-AS2, a promising prognostic biomarker, reveals a new dimension into the molecular pathogenesis of CRC and provides a prospective treatment target for this disease.

A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer.

BACKGROUND: Gastric cancer (GC) is characterised by a heterogeneous tumour microenvironment (TME) that is closely associated with the response to treatment, especially immunotherapies. However, most previous GC molecular subtyping systems need complex gene signatures and examination methods, restricting their clinical applications. Thus, we developed a new TME-based molecular subtype using only two genes. METHODS: Nine independent GC cohorts at the tissue- or single-cell level with more than 2000 patients were used in this study, including data we examined by single-cell sequencing, quantitative RT-PCR and immunochemistry/immunofluorescence staining. Nine different methods, five existing molecular subtypes and a series of signatures were used to evaluate the TME and molecular characteristics of GC. RESULTS: We established a CTSL/ZBTB7B subtyping system and uncovered the novel CTSLHighZBTB7BLow high-risk subgroup, but characterised by relative higher immune cell infiltration and lower tumour purity. This subgroup demonstrate higher levels of immune checkpoints and more enrichment of cancer-related pathways compared with other cases. CONCLUSIONS: We identified a high-risk subpopulation with unique TME features based on expressions of CTSL and ZBTB7B, suggesting a counterbalancing phenotype between immunostimulatory and immunosuppressive mechanisms. This subtyping system could be used to select treatment and management strategies for GC.

Hierarchical Fibrous Honeycomb Ceramics with High Load Capability and Low Light-Off Temperature for the Next-Generation Auto Emissions Standards.

Novel and stringent automotive exhaust gas emissions standards are urgently needed to counter the problems posed by the worsening global climate and environment. However, the traditional cordierite-based honeycomb ceramics substrates with ultimate pore density have seriously restricted the establishment of new emission standards. Herein, we introduce a novel robust substrate with tailored volume-specific surface area and low heat capacity. This substrate employs the synergy of high-strength ceramic fibers and ultrathin TiO2 nanosheets. The micro-sized fibers provide support to ensure structural strength during the catalytic reaction, while the nanosheets play the dual role of connecting the fibers and providing a high surface area for catalyst immobilization. The new three-dimensional (3D) microarchitecture exhibits a high volume-specific surface area of 3.59×104  cm2 /cm3 , a compressive strength of 2.01 MPa, and remarkable stability after high-speed air erosion at 800 °C. The honeycomb-like structure exhibit low resistance to gas flow. Furthermore, after loading with Pt and Pd nanoparticles, the composite 3D microarchitecture delivered an excellent catalytic performance and prominent structural stability, with a super low light-off temperature of 150 °C. The outstanding mechanical and thermal stability and the high surface area and light-off temperature of the new substrate indicate its potential for use as a highly efficient catalytic carrier to meet the next-generation auto emissions standards.

Synthesis and Applications of SAPO-34 Molecular Sieves.

Silicoaluminophosphate zeolite (SAPO-34) has been attracting increasing attention due to its excellent form selection and controllability in the chemical industry, as well as being one of the best industrial catalysts for methanol-to-olefin (MTO) reaction conversion. However, as a microporous molecular sieve, SAPO-34 easily generates carbon deposition and rapidly becomes inactivated. Therefore, it is necessary to reduce the crystal size of the zeolite or to introduce secondary macropores into the zeolite crystal to form a hierarchical structure in order to improve the catalytic effect. In this review, the synthesis methods of conventional SAPO-34 molecular sieves, hierarchical SAPO-34 molecular sieves and nanosized SAPO-34 molecular sieves are introduced, and the properties of the synthesized SAPO-34 molecular sieves are described, including the phase, morphology, pore structure, acid source, and catalytic performance, in particular with respect to the synthesis of hierarchical SAPO-34 molecular sieves. We hope that the review can provide guidance to the preparation of the SAPO-34 catalysts, and stimulate the future development of high-performance hierarchical SAPO-34 catalysts to meet the growing demands of the material and chemical industries.

SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling.

BACKGROUND: SLCO4A1-AS1 was found to be upregulated in several cancer types, including colorectal cancer (CRC). However, the detailed roles of SLCO4A1-AS1 in CRC remain to be elucidated. Therefore, we investigated the functions, mechanism, and clinical significance of SLCO4A1-AS1 in colorectal tumourigenesis. METHODS: We measured the expression of SLCO4A1-AS1 in CRC tissues using qRT-PCR and determined its correlation with patient prognosis. Promoter methylation analyses were used to assess the methylation status of SLCO4A1-AS1. Gain- and loss-of-function assays were used to evaluate the effects of SLCO4A1-AS1 on CRC growth in vitro and in vivo. RNA pull-down, RNA immunoprecipitation, RNA-seq, luciferase reporter and immunohistochemistry assays were performed to identify the molecular mechanism of SLCO4A1-AS1 in CRC. RESULTS: SLCO4A1-AS1 was frequently upregulated in CRC tissues based on multiple CRC cohorts and was associated with poor prognoses. Aberrant overexpression of SLCO4A1-AS1 in CRC is partly attributed to the DNA hypomethylation of its promoter. Ectopic SLCO4A1-AS1 expression promoted CRC cell growth, whereas SLCO4A1-AS1 knockdown repressed CRC proliferation both in vitro and in vivo. Mechanistic investigations revealed that SLCO4A1-AS1 functions as a molecular scaffold to strengthen the interaction between Hsp90 and Cdk2, promoting the protein stability of Cdk2. The SLCO4A1-AS1-induced increase in Cdk2 levels activates the c-Myc signalling pathway by promoting the phosphorylation of c-Myc at Ser62, resulting in increased tumour growth. CONCLUSIONS: Our data demonstrate that SLCO4A1-AS1 acts as an oncogene in CRC by regulating the Hsp90/Cdk2/c-Myc axis, supporting SLCO4A1-AS1 as a potential therapeutic target and prognostic factor for CRC.

Prenatal Bisphenol A Exposure and Early Childhood Behavior and Cognitive Function: A Chinese Birth Cohort Study.

INTRODUCTION: Biomonitoring of bisphenol A (BPA) in human blood is still scarce, although already noticeable. We aimed to examine the associations between prenatal serum BPA concentrations and behavior and cognitive function in preschool children. METHODS: A total of 1,782 mother-child pairs with complete demographic information, blood samples, and psychological measurements were included from the China-Anhui Birth Cohort (C-ABCS). We detected serum BPA concentrations and assessed children's neurodevelopment using a set of psychometric scales. RESULTS: The median prenatal maternal serum BPA concentration was 0.23 (P25, P75: 0.07, 0.52) ng/mL, with a detection frequency of 85.19%. Compared with the girls with the lowest concentrations, those with highest BPA concentrations had increased risks of inhibitory self-control impairment [relative risk (RR) = 3.66, 95% confidence interval (CI): 1.53, 7.58], emergent metacognition impairment (RR = 1.70, 95% CI: 1.07, 2.78), conduct problem (RR = 1.68, 95% CI: 1.12, 2.39), peer relationship problem (RR = 2.57, 95% CI: 1.33, 4.47), higher total difficulties score (RR = 1.76, 95% CI: 1.12, 2.67), and higher impact factor score (RR = 1.52, 95% CI: 1.11, 2.05), while the boys with the highest prenatal BPA concentrations had an increased risk of conduct problem compared with those with the lowest concentrations (RR = 1.59, 95% CI: 1.09, 2.24) (P-interaction = 0.011). After stratification by age, high prenatal BPA concentrations were associated with increased ADHD (RR = 4.44, 95% CI: 1.54, 10.85) among children aged 3 years, not among children aged 4 years. CONCLUSION: Our study revealed the sex-specific and age-specific impacts of prenatal BPA exposure on preschool children's cognitive and behavioral development.