An exploration of causal relationships between nine neurological diseases and the risk of breast cancer: a Mendelian randomization study.

BACKGROUND: Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However, whether there are causal relationships between these neurological conditions and breast cancer is inconclusive. This study was designed to explore whether neurological disorders affected the risks of breast cancer overall and of the two subtypes (ER+ and ER-). METHODS: In the course of this study, genome-wide association study (GWAS) data for nine neurological diseases (Alzheimer's disease, multiple sclerosis, Parkinson's disease, myasthenia gravis, generalized epilepsy, intracerebral haemorrhage, cerebral atherosclerosis, brain glioblastoma, and benign meningeal tumour) were collected from the Complex Trait Genetics lab and the MRC Integrative Epidemiology Unit, and single-nucleotide polymorphisms (SNPs) extensively associated with these neurological ailments had been recognized as instrumental variables (IVs). GWAS data on breast cancer were collected from the Breast Cancer Association Consortium (BCAC). Two-sample Mendelian randomization (MR) analyses as well as multivariable MR analyses were performed to determine whether these SNPs contributed to breast cancer risk. Additionally, the accuracy of the results was evaluated using the false discovery rate (FDR) multiple correction method. Both heterogeneity and pleiotropy were evaluated by analyzing sensitivities. RESULTS: According to the results of two-sample MR analyses, Alzheimer's disease significantly reduced the risks of overall (OR 0.925, 95% CI [0.871-0.982], P = 0.011) and ER+ (OR 0.912, 95% CI [0.853-0.975], P = 0.007) breast cancer, but there was a negative result in ER- breast cancer. However, after multiple FDR corrections, the effect of Alzheimer's disease on overall breast cancer was not statistically significant. In contrast, multiple sclerosis significantly increased ER+ breast cancer risk (OR 1.007, 95% CI [1.003-1.011], P = 0.001). In addition, the multivariable MR analyses showed that Alzheimer's disease significantly reduced the risk of ER+ breast cancer (IVW: OR 0.929, 95% CI [0.864-0.999], P=0.047; MR-Egger: OR 0.916, 95% CI [0.846-0.992], P=0.031); however, multiple sclerosis significantly increased the risk of ER+ breast cancer (IVW: OR 1.008, 95% CI [1.003-1.012], P=4.35×10-4; MR-Egger: OR 1.008, 95% CI [1.003-1.012], P=5.96×10-4). There were no significant associations between the remainder of the neurological diseases and breast cancer. CONCLUSIONS: This study found the trends towards a decreased risk of ER+ breast cancer in patients with Alzheimer's disease and an increased risk in patients with multiple sclerosis. However, due to the limitations of Mendelian randomization, we cannot determine whether there are definite causal relationships between neurological diseases and breast cancer risk. For conclusive evidences, more prospective randomized controlled trials will be needed in the future.

Serum PM20D1 levels in patients with idiopathic pulmonary arterial hypertension and its clinical significance.

OBJECTIVE: This study aimed to investigate the serum levels of Peptidase M20 domain containing 1 (PM20D1) in idiopathic pulmonary arterial hypertension (IPAH) patients and examine its association with lipid metabolism, echocardiography, and hemodynamic parameters. METHODS: This prospective observational research enrolled 103 IPAH patients from January 2018 to January 2022. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum PM20D1 levels in all patients before treatment within 24 h of admission. Demographic data, echocardiography, hemodynamic parameters and serum biomarkers were also collected. RESULTS: The IPAH patients in the deceased group had significantly elevated age, right atrial (RA), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR) and significantly decreased 6 min walking distance (6MWD) and tricuspid annulus peak systolic velocity (TASPV). IPAH patients showed significant decreases in serum PM20D1, low-density lipoprotein cholesterol (LDL-C), and albumin (ALB). Additionally, PM20D1 was negatively correlated with RA, NT-proBNP and positively correlated with PVR, ALB, 6MWD, and TAPSV. Moreover, PM20D1 has the potential as a biomarker for predicting IPAH patients' prognosis. Finally, logistic regression analysis indicated that PM20D1, ALB, NT-proBNP, PVR, TASPV, RA and 6MWD were identified as risk factors for mortality in IPAH patients. CONCLUSION: Our findings indicated that the serum levels of PM20D1 were significantly decreased in IPAH patients with poor prognosis. Moreover, PM20D1 was identified as a risk factor associated with mortality in IPAH patients.

An exploratory study of whether axillary lymph node dissection can be avoided in breast cancer patients with positive lymph nodes.

Background: Breast cancer patients with positive axillary lymph nodes usually require axillary lymph node dissection (ALND), with many postoperative complications, such as lymphedema. For these patients, whether sentinel lymph node biopsy (SLNB) can replace ALND has been a research hotspot in the field of breast cancer. This study developed two risk stratification models for predicting the clinical outcomes of breast cancer patients with positive axillary lymph nodes receiving SLNB alone or ALND to determine which patients could potentially avoid ALND. Methods: A total of 21,942 breast cancer patients, including a training set (n=15,362) and a testing set (n=6,580), were enrolled in this study from Surveillance, Epidemiology, and End Results (SEER) between 2000 and 2017. The risk factors associated with breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using multivariate Cox regression analysis and then integrated into nomograms and risk stratification models examined by receiver operating characteristic (ROC) curves and calibration curves. The survival discrepancies were compared between the SLNB and ALND subgroups with different risk scores with Kaplan-Meier plots. Results: In multivariate Cox regression analyses, grade, marital status, T stage, radiotherapy and lymph node metastasis (GMTRL) were independent risk factors in breast cancer patients with both OS and BCSS status in the ALND cohort from the training set. Nomograms have been developed based on these factors to predict 3- and 5-year OS and BCSS in patients with ALND. Calibration curves and ROC curves in both the training and testing sets confirmed the excellent overall predictive performance of the nomograms. Furthermore, we developed two risk stratification models based on OS and BCSS status, revealing that patients with low GMTRL scores might avoid ALND in both OS and BCSS status [OS: hazard ratio (HR) =0.929, 95% confidence interval (CI): 0.841-1.027, P=0.150; BCSS: HR =0.953, 95% CI: 0.831-1.094, P=0.495], but patients with moderate (OS: HR =0.756, 95% CI: 0.666-0.859, P<0.001; BCSS: HR =0.643, 95% CI: 0.537-0.768, P<0.001) and high GMTRL scores could not (OS: HR =0.719, 95% CI: 0.549-0.940, P=0.014; BCSS: HR =0.731, 95% CI: 0.549-0.974, P=0.031). Conclusions: Breast cancer patients with positive nodes could be treated with SLNB alone rather than ALND without affecting prognosis based on GMTRL scores. Patients with high or moderate GMTRL scores benefited greatly from ALND, but not for patients with low GMTRL scores. This study may assist clinicians in tailoring treatments.

Circularly polarized blue fluorescence based on chiral heteroleptic six-coordinate bis-pyrazolonate-Zn2+ complexes.

Applying molecular design to chiral organo-Zn2+ complexes, a new pair of chiral heteroleptic bis-pyrazolonate-Zn2+ enantiomers [Zn(PMBP)2(1R,2R-Chxn)] (R,R-Zn2+; HPMBP = 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone and 1R,2R-Chxn = (1R,2R)-cyclohexane-1,2-diamine) and [Zn(PMBP)2(1S,2S-Chxn)] (S,S-Zn2+; 1S,2S-Chxn = (1S,2S)-cyclohexane-1,2-diamine) have been synthesized and characterized in terms of photophysical and thermodynamic properties. In addition to a small Flack parameter (0.05(3)) associated with the solid-state elucidation of S,S-Zn2+, the circular dichroism (CD) and circularly polarized light (CPL) spectra for the chiral Zn2+ enantiomers show perfect mirror symmetry, establishing that the enantiopure 1,2-diamines successfully induce the optical isomerism of R,R-Zn2+ and S,S-Zn2+. As a result of the combined strong chiral induction capability of chiral 1,2-diamines and excellent photophysical properties of the pyrazolone ligand (PMBP)-, the two Zn2+ enantiomers exhibit high-quality pure blue fluorescence (ΦPL = 9-10%) and significant CPL activity (|glum| = 0.0065-0.0068). The heteroleptic strategy adopted in this study offers a new route to develop high-performance chiroptical luminophores.

Superhydrophobic Co-MOF-based sponge for efficient oil-water separation utilizing photothermal effect.

Effectively addressing crude oil spills remains a global challenge due to its high viscosity and limited flow characteristics. In this study, we successfully prepared a modified sponge (PCP@MS) by embedding the photothermal material of Co-HHTP and coating the melamine sponge (MS) with low-surface-energy polydimethylsiloxane (PDMS). The PCP@MS exhibited outstanding hydrophobicity with WCA of 160.2° and high oil absorption capacity of 59-107 g/g. The PCP@MS showed high separation efficiency of 99.2% for various oil-water mixtures, along with notable self-cleaning properties and mechanical stability. The internal micro-nano hierarchical structure on the sponge surface significantly enhanced light absorption, synergizing with the photo-thermal conversion properties of Co-HHTP, enabled PCP@MS to achieve a surface temperature of 109.2 °C under 1.0 solar light within 300 s. With the aid of solar radiation, PCP@MS is able to heat up quickly and successfully lowering the viscosity of the surrounding crude oil, resulting in an oil recovery rate of 8.76 g/min. Density functional theory (DFT) calculation results revealed that Co-HHTP featured a zero-gap band structure, rendering advantageous electronic properties for full-wavelength light absorption. This in situ solar-heated absorbent design is poised to advance the practical application of viscous oil spill cleanup and recovery.

Novel Binder with Cross-Linking Reconfiguration Functionality for Silicon Anodes of Lithium-Ion Batteries.

Silicon is expected to be used as a high theoretical capacity anode material in lithium-ion batteries with high energy densities. However, the huge volume change incurred when silicon de-embeds lithium ions, leading to destruction of the electrode structure and a rapid reduction in battery capacity. Although binders play a key role in maintaining the stability of the electrode structure, commonly used binders cannot withstand the large volume expansion of the silicon. To alleviate this problem, we propose a PGC cross-linking reconfiguration binder based on poly(acrylic acid) (PAA), gelatin (GN), and ß-cyclodextrin (ß-CD). Within PGC, PAA supports the main chain and provides a large number of carboxyl groups (-COOH), GN provides rich carboxyl and amide groups that can form a cross-linking network with PAA, and ß-CD offers rich hydroxyl groups and a cone-shaped hollow ring structure that can alleviate stress accumulation in the polymer chain by forming a new dynamic cross-linking coordination conformation during stretching. In the half cell, the silicon negative prepared by the PGC binder exhibited a high specific capacity and capacity maintenance ratio, and the specific capacity of the silicon negative electrode prepared by the PGC binder is still 1809 mAh g-1 and the capacity maintenance ratio is 73.76% following 200 cycles at 2 A g-1 current density, indicating that PGC sufficiently maintains the silicon negative structure during the battery cycle. The PGC binder has a simple preparation method and good capacity retention ability, making it a potential reference for the further development of silicon negative electrodes.

A Vancomycin-Templated DNA-Encoded Library for Combating Drug-Resistant Bacteria.

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.

Lanthanide MOFs based portable fluorescence sensing platform: Quantitative and visual detection of ciprofloxacin and Al3.

In the current context of water environmental monitoring and pollution control, there's a crucial need for rapid and simple methods to detect multi-pollutant. We herein report an easy one-step hydrothermal synthesis method to produce Eu-based metal-organic frameworks (Eu MOFs), which was used as a fluorescent probe to detect the aquatic environmental pollutants of ciprofloxacin (CIP) and aluminum ions (Al3+). This fluorescent sensor enabled the cascade detection of CIP and Al3+ through fluorescence enhancement and ratio fluorescence response, respectively. The introduction of CIP significantly turned on the characteristic fluorescence of Eu MOFs at 595 nm and 616 nm through the "antenna effect". Based on this, the sensor enables quantitative detection of CIP within a linear range of 0-120 µM with a LOD as low as 50.421 nM. In the presence of Al3+, the fluorescence emission of Eu MOFs-CIP was sharply turned off due to strong Al3+ coordination with CIP, while the blue fluorescence emission of CIP was remarkably enhanced. And thus allowing ratio fluorescence quantitative detection of Al3+ (LOD = 2.681 µM). The introduction of CIP and Al3+ in cascade resulted in distinct fluorescence color changes from colorless to red and eventually to blue, exhibiting pronounced fluorescence characteristics. This observable phenomenon enables the visual detection of CIP and Al3+ in both aqueous phase and paper test strips. By combining the analysis of fluorescence chromaticity with the use of a smartphone, the fluorescence color of test papers allows for simple quantitative determination, which provides a convenient and accessible approach for quantifying CIP and Al3+ in water environments.

Amidation-Reaction Strategy Constructs Versatile Mixed Matrix Composite Membranes towards Efficient Volatile Organic Compounds Adsorption and CO2 Separation.

Mixed matrix composite membranes (MMCMs) have shown advantages in reducing VOCs and CO2 emissions. Suitable composite layer, substrate, and good compatibility between the filler and the matrix in the composite layer are critical issues in designing MMCMs. This work develops a high-performance UiO-66-NA@PDMS/MCE for VOCs adsorption and CO2 permea-selectivity, based on a simple and facile fabrication of composite layer using amidation-reaction approach on the substrate. The composite layer shows a continuous morphological appearance without interface voids. This outstanding compatibility interaction between UiO-66-NH2 and PDMS is confirmed by molecular simulations. The Si─O functional group and UiO-66-NH2 in the layer leads to improved VOCs adsorption via active sites, skeleton interaction, electrostatic interaction, and van der Waals force. The layer and ─CONH─ also facilitate CO2 transport. The MMCMs show strong four VOCs adsorption and high CO2 permeance of 276.5 GPU with a selectivity of 36.2. The existence of VOCs in UiO-66-NA@PDMS/MCE increases the polarity and fine-tunes the pore size of UiO-66-NH2 , improving the affinity towards CO2 and thus promoting the permea-selectivity for CO2 , which is further verified by GCMC and EMD methods. This work is expected to offer a facile composite layer manufacturing method for MMCMs with high VOC adsorption and CO2 permea-selectivity.

Compact gas cell for simultaneous detection of atmospheric aerosol optical properties based on photoacoustic spectroscopy and integrating sphere scattering enhancement.

Atmospheric aerosols play a pivotal role in the earth-atmospheric system. Analyzing their optical properties, specifically absorption and scattering coefficients, is essential for comprehending the impact of aerosols on climate. When different optical properties of aerosols are individually measured using multiple devices, cumulative errors in the detection results inevitably occur. To address this challenge, based on photoacoustic spectroscopy (PAS) and integrating sphere (IS) scattering enhancement, a compact gas cell (PASIS-Cell) was developed. The PASIS-Cell comprises a dual-T-type photoacoustic cell (DTPAC) and an IS. IS is coupled with DTPAC through a transparent quartz tube, thereby enhancing the scattering signal without compromising the acoustic characteristics of DTPAC. Concurrently, DTPAC can realize high-performance photoacoustic detection of absorption signal. Experimental results demonstrate that PASIS-Cell can simultaneously invert atmospheric aerosol absorption and scattering coefficients, with a minimum detection limit of less than 1 Mm-1, showcasing its potential in the analysis of aerosol optical properties.

Effect of Glycine on the Wet Carbonation of Steel Slag Used as a Cementitious Material.

The wet carbonation process of steel slag (SS) is envisaged to be an effective way to sequestrate CO2 and improve the properties of SS as a supplementary cementitious material. However, the carbonation process still struggles with having a low carbonation efficiency. This paper studied the effect of glycine on the accelerated carbonation of SS. The phase composition change of carbonated SS was analyzed via XRD, FT-IR, and TG-DTG. The carbonation process of SS is facilitated by the assistance of glycine, with which the carbonation degree is increased. After 60 min of carbonation, SS with glycine obtained a CO2 sequestration rate of 9.42%. Meanwhile, the carbonation reaction could decrease the content of free calcium oxide in SS. This significantly improves the soundness of SS-cement cementitious material, and the compressive strength of cementitious materials that contain carbonated SS with glycine is improved. Additionally, the cycling performance of glycine in the successive wet carbonation process of SS was investigated. Multicycle experiments via solvent recovery demonstrated that although the promotion effect of glycine was reduced after each cycle, compared with the SS-water system, the carbonation process could still be facilitated, demonstrating that successive wet carbonation via solvent recovery has considerable potential. Herein, we provide a new idea to facilitate the wet carbonation process of SS and improve the properties of SS-cement cementitious material.

Influence of Silane Coupling Agent and Anionic Dispersant on the Dispersion Effect of Silicon Carbide Particles.

Silicon carbide (SiC), as a widely used material, has great properties. To improve the flowability of ultrafine silicon carbide slurry, this study used sodium humate, tetramethylammonium hydroxide (TMAH), and N-(ß-monoaminoethyl)-γ-aminopropyltrimethyl(ethoxysilane) (KH792) to modify the ultrafine silicon carbide powder produced by Qingzhou Micro Powder Company. The effects of different modifiers on improving the flowability of ultrafine silicon carbide slurry were investigated by means of viscosity tests, sedimentation experiments, and SEM observations. Their modification mechanisms were investigated by means of zeta potential tests, XPS tests, and so on. In this paper, the initial modification of SiC was carried out with KH792, followed by the secondary modification with anionic and cationic modifiers (tetramethylammonium hydroxide and sodium humate), and the optimal modification conditions were investigated by means of a viscosity test, which showed that the lowest viscosity of the modified SiC reached 0.076 Pa·s and that the absolute maximum value of the zeta potential increased from 47.5 at the time of no modification to 63.7 (maximum values) at the time of modification. This means it has an improved surface charge, which improves dispersion. The adsorption results of the modifier on the silicon carbide surface were also demonstrated by the XPS test results.

Effect of two different crystal forms of alumina on hydration properties and mechanical properties of steel slag-cement composite cementitious materials.

In the present work, two common nano-alumina (NA) with different crystal forms (α-NA and γ-NA) are used to research the effects of steel slag-cement composite cementitious materials, which include the hydration properties and mechanical properties. The results show that the NA can enhance the strength of steel slag-cement composite cementitious materials, especially the early strength. Meanwhile, when the addition amount of γ-NA was 1%, the maximum compressive strength and flexural strength at 28 d were 35.43 and 5.21 MPa, respectively; when the addition amount of α-NA was 3%, the maximum compressive strength and flexural strength at 28 d were 36.27 and 4.89 MPa, respectively. In addition, according to the analysis of X-ray diffractometer and differential thermal analysis, it was concluded that the effects of the two types of alumina on the strength were mainly pozzolanic effect and filling effect. The pozzolanic effect of γ-NA was significantly stronger than that of α-NA. However, the large surface area of γ-NA affected the dispersion of the particles and the filling effect. According to scanning electron microscope analysis, compared with α-NA, γ-NA had significantly more hydration products and tighter adhesion. In conclusion, the addition of NA not only improved the properties but further realized the value-added utilization of steel slag.

Adsorption and Dispersion Effect of Sodium Lignosulfonate on Fine SiC Particles in Aqueous Media.

This study presented a novel modification method for fine SiC powder by using sodium lignosulfonate as a dispersant. The adsorption behavior of sodium lignosulfonate on the SiC/water interface and its effect on the performance of a fine SiC slurry were systematically investigated. The adsorption results showed that sodium lignosulfonate formed monolayer adsorption on the surface of fine SiC and that the saturated adsorption capacity was 1.3263 mg/g. The adsorption reached equilibrium within 3 h and was mainly controlled by active sites on the SiC surface. The dispersion, stability, and zeta potential of modified SiC powder were improved after sodium lignosulfonate adsorption. The zeta potential of modified SiC reached a minimum value of -44.8 mV at pH 12. Modified SiC suspensions had great stability in a wider pH range of 6-12. Modified SiC slurry with 54 vol % solid loading had a low viscosity of 173 mPa·s at pH 10. Subsequently, coarse SiC powder was added for slip casting. A mixed slurry with high solid loading (69 vol %) and low viscosity (583 mPa·s) was prepared using modified SiC and coarse SiC powders at a mass ratio of 2:3. Finally, recrystallized SiC green body with high density (2.6492 g/cm3) was obtained.

Applications of photodynamic therapy in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare form of adenocarcinoma usually found in apocrine gland-containing cutaneous regions. EMPD affects the vulvar area most commonly, followed by the perianal area, scrotum, penis, and axillary region. In its initial form, EMPD presents as an erythematous plaque with well-defined edges, fine scaling, excoriations, exulcerations, and lichenification. Generally, a definitive diagnosis can be made through histopathological analysis. Importantly, associated malignancies should be investigated prior to treatment initiation. Photodynamic therapy (PDT) is a modern, noninvasive treatment strategy for non-oncological diseases as well as various cancers. In recent years, PDT has been widely used to treat EMPD. This present article presents a discussion of the diagnosis and treatment of EMPD as well as the usefulness of PDT in its management.

Deep learning-enabled 3D multimodal fusion of cone-beam CT and intraoral mesh scans for clinically applicable tooth-bone reconstruction.

High-fidelity three-dimensional (3D) models of tooth-bone structures are valuable for virtual dental treatment planning; however, they require integrating data from cone-beam computed tomography (CBCT) and intraoral scans (IOS) using methods that are either error-prone or time-consuming. Hence, this study presents Deep Dental Multimodal Fusion (DDMF), an automatic multimodal framework that reconstructs 3D tooth-bone structures using CBCT and IOS. Specifically, the DDMF framework comprises CBCT and IOS segmentation modules as well as a multimodal reconstruction module with novel pixel representation learning architectures, prior knowledge-guided losses, and geometry-based 3D fusion techniques. Experiments on real-world large-scale datasets revealed that DDMF achieved superior segmentation performance on CBCT and IOS, achieving a 0.17 mm average symmetric surface distance (ASSD) for 3D fusion with a substantial processing time reduction. Additionally, clinical applicability studies have demonstrated DDMF's potential for accurately simulating tooth-bone structures throughout the orthodontic treatment process.

JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin.

BACKGROUND: Proteins containing the Jumonji C (JmjC) domain participated in tumorigenesis and cancer progression. However, the mechanisms underlying this effect are still poorly understood. Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2 (JARID2) - a JmjC family protein - in breast cancer, as well as its latent association with obesity. METHODS: Immunohistochemistry, The Cancer Genome Atlas, Gene Expression Omnibus, and other databases were used to analyze the expression of JARID2 in breast cancer cells. Growth curve, 5-ethynyl-2-deoxyuridine (EdU), colony formation, and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion. Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates. Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2. The results were further verified using co-immunoprecipitation and glutathione S-transferase (GST) pull-down experiments. Using chromatin immunoprecipitation (ChIP) sequencing, we sought the target genes that JARID2 and metastasis-associated protein 1 (MTA1) jointly regulated; the results were validated by ChIP-PCR, quantitative ChIP (qChIP) and ChIP-reChIP assays. A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes. RESULTS: In this study, we found that JARID2 was highly expressed in multiple types of cancer including breast cancer. JARID2 promoted glycolysis, lipid metabolism, proliferation, invasion, and stemness of breast cancer cells. Furthermore, JARID2 physically interacted with the nucleosome remodeling and deacetylase (NuRD) complex, transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated (BRCA2), RB transcriptional corepressor 1 (RB1), and inositol polyphosphate-4-phosphatase type II B (INPP4B). Additionally, JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the breast cancer microenvironment. Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer. CONCLUSION: Our data indicated that JARID2 promoted breast tumorigenesis and development, confirming JARID2 as a target for cancer treatment.

Design, Construction, and Screening of Diversified Pyrimidine-Focused DNA-Encoded Libraries.

Pyrimidine is a ubiquitous component in natural products and approved drugs, providing an ideal modular scaffold for generating libraries with drug-like properties. DNA-encoded library technology introduces a novel library modality where each small molecule is covalently linked to a unique oligo tag. This technology offers the advantages of rapidly generating and interrogating large-scale libraries containing billions of members, substantially reducing the entry barrier to their use in both academia and the pharmaceutical industry. In this Letter, we describe the synthesis of three DNA-encoded libraries based on different functionalized pyrimidine cores featuring diversified chemoselectivity and regioselectivity. Preliminary screening of these DNA-encoded libraries against BRD4 identified compounds with nanomolar inhibition activities.

Double-time-scale non-probabilistic reliability-based controller optimization for manipulator considering motion error and wear growth.

Motion error and wear growth are two crucial factors that determine the performance of the manipulator system. The two factors are distinct from the sensitivity to time and respectively indicate its control performance and lifespan level. In this paper, a double-time-scale non-probabilistic reliability (DTSNPR)-based optimization method, which considers time-sensitive factor motion error as time-dependent reliability (TDR) and time-insensitive factor clearance wear growth as time-independent reliability (TIR), is proposed to comprehensively evaluate and optimize the controller of the manipulator system in consideration of these multi-scale factors. Meanwhile, for a highly nonlinear response problem of a manipulator system, the adaptive subinterval collocation method (ASICM) which transfers the highly nonlinear uncertainty propagation problem into a sequence of small subintervals, is adopted to obtain the response range more precisely. The proposed DTSNPR-based optimization method is applied to three numerical manipulator systems and ensures each of them under a predefined level of reliability upon both motion error and wear growth. The results also indicate that the proposed ASICM owns an advantage over computational cost and precision, with only 0.4% error and 1% computational cost compared with the Monte-Carlo methods.