Discovery of Novel 5-Cyano-3-phenylindole-Based LSD1/HDAC Dual Inhibitors for Colorectal Cancer Treatment.

The dual inhibition of histone lysine-specific demethylase 1 (LSD1) and histone deacetylase (HDAC) has emerged as a promising strategy for cancer therapy. In this study, we report the discovery of novel 5-cyano-3-phenylindole-based LSD1/HDAC dual inhibitors, evaluated through both in vitro and in vivo assays. Among these inhibitors, compound was identified as particularly potent, exhibiting high inhibitory activity against LSD1 (IC = 39.

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

Objective: Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors.

Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening.

PHD fingers are a type of chromatin reader that primarily recognize chromatin as a function of lysine methylation state. Dysregulated PHD fingers are implicated in various human diseases, including acute myeloid leukemia. Targeting PHD fingers with small molecules is considered challenging as their histone tail binding pockets are often shallow and surface-exposed.

Identification and Optimization of Small Molecule Pyrazolopyrimidine TLR7 Agonists for Applications in Immuno-oncology.

Small molecule toll-like receptor (TLR) 7 agonists have gathered considerable interest as promising therapeutic agents for applications in cancer immunotherapy. Herein, we describe the development and optimization of a series of novel TLR7 agonists through systematic structure-activity relationship studies focusing on modification of the phenylpiperidine side chain. Additional refinement of ADME properties culminated in the discovery of compound , which displayed nanomolar reporter assay activity and favorable drug-like properties.

Changes in frailty and depressive symptoms among middle-aged and older Chinese people: a nationwide cohort study.

Background And Aims: The older people bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the older Chinese people have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and older adults.

Methods: The study used four waves of data from 2011, 2013, 2015 and 2018 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and older people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models.

New caffeoyl derivatives with potent DPPH radical scavenging activity from .

Eight new caffeoyl derivatives, elephantomentosides A-H (-), together with ten known ones (-), were isolated from the whole plant of L. Their structures were elucidated using detailed spectroscopic analysis. Structurally, compounds - are composed of -D-glucopyranose, and almost all of the substituent positions are at the C-1' and C-4' of glucopyranose.

Singlet oxygen induces cell wall thickening and stomatal density reducing by transcriptome reprogramming.

Singlet oxygen (O) has a very short half-life of 10 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of O and shows drastic changes in nuclear gene expression.

The prevalence and influencing factors of frailty in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: To investigate the prevalence and influencing factors of frailty and pre-frailty in chronic kidney disease (CKD) patients and thereby provide a scientific basis for effective avoidance of frailty in patients with CKD.

Methods: PubMed, EMBASE, Web of Science, EBSCO, Cochrane Library, CNKI, VIP, CBMdisc, and Wanfang databases were searched for relevant studies published till December 31, 2021. The summary results were described as odds ratios (ORs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs).

Nivalenol disrupts mitochondria functions during porcine oocyte meiotic maturation.

Oocyte maturation is important for fertility in mammals, since the quality of oocytes directly affects fertilization, embryo attachment and survival. Nivalenol is widely present in nature as a common toxin that contaminates grain and feed, and it has been reported to cause acute toxicity, immunotoxicity, reproductive toxicity and carcinogenic effects. In this study, we explored the impact of nivalenol on the porcine oocyte maturation and its possible mechanisms.

Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study.

Background: cumulative evidence from cohort studies suggested that there were inconsistent conclusions as to whether there was a bidirectional association between depression and frailty. Therefore, this study used a bidirectional two-sample Mendelian randomisation (MR) study to investigate the causal relationship between depression and frailty.

Methods: we performed univariate and multivariate bidirectional MR analyses to assess the causal association between depression and frailty.

Crafting a place-based souvenir for sustaining cultural heritage.

This study aims to investigate the souvenir-person-place bonding for sustaining cultural heritage. Previous studies acknowledge souvenirs could represent a place; however, how people perceive souvenirs as representative of the place still needs to be studied. This study comprehends the traditional craft by identifying the dimensions of place-based craft souvenirs and exploring the connections between souvenirs, craft, and place.

Ratiometric detection of I using a dysprosium-based metal-organic framework with a single emission center.

In this study, a dysprosium-based metal-organic framework (MOF) sensor (Dy-MOF) was developed for the ratiometric detection of I in aqueous medium. Upon excitation at 230 nm, Dy-MOF shows two dominant emission bands at 464 nm and 574 nm assigned to (F, D) → H + F and F → H transition of Dy, respectively, which have different sensitivities toward iodide ions. The introduction of I slightly weakened the blue emission at 464 nm and significantly quenched the yellow emission at 574 nm.

A ratiometric luminescence sensing platform based on lanthanide-based silica nanoparticles for selective and sensitive detection of Fe and Cu ions.

Detection of Fe(III) and Cu(II) in water is highly desirable because their abnormal levels can cause serious harm to human health and environmental safety. In this work, a ratiometric luminescence sensing platform based on lanthanide-based silica nanoparticles was constructed for the detection of Fe and Cu ions. The terbium-silica nanoparticles (named SiO@Tb) with dual-emission signals were successfully prepared by grafting Tb ions onto trimellitic anhydride (TMA) functionalized silica nanospheres.

Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study.

Currently, the causal association between sleep disorders and rheumatoid arthritis (RA) has been poorly understood. In this two-sample Mendelian randomization (TSMR) study, we tried to explore whether sleep disorders are causally associated with RA. Seven sleep-related traits were chosen from the published Genome-Wide Association Study (GWAS): short sleep duration, frequent insomnia, any insomnia, sleep duration, getting up, morningness (early-to-bed/up habit), and snoring, 27, 53, 57, 57, 70, 274, and 42 individual single-nucleotide polymorphisms (SNPs) ( < 5 × 10) were obtained as instrumental variables (IVs) for these sleep-related traits.

Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study.

A correlation between sleep and systemic lupus erythematosus (SLE) has been observed in a number of prior investigations. However, little is known regarding the potential causative relationship between them. In this study, we selected genetic instruments for sleep traits from pooled data from published genome-wide association studies (GWAS).

Covalent labeling of a chromatin reader domain using proximity-reactive cyclic peptides.

Chemical probes for chromatin reader proteins are valuable tools for investigating epigenetic regulatory mechanisms and evaluating whether the target of interest holds therapeutic potential. Developing potent inhibitors for the plant homeodomain (PHD) family of methylation readers remains a difficult task due to the charged, shallow and extended nature of the histone binding site that precludes effective engagement of conventional small molecules. Herein, we describe the development of novel proximity-reactive cyclopeptide inhibitors for PHD3-a trimethyllysine reader domain of histone demethylase KDM5A.

Neuron-Specific Enolase and Hemoglobin as Risk Factors of Intraocular Metastasis in Patients with Renal Cell Carcinoma.

Renal cell carcinoma (RCC) appears to be a high risk of spread. This research investigated the correlation between a different range of clinical features and intraocular metastasis (IOM) in RCC patients and attempted to determine potential risk factors of RCC patients with IOM. In the study, there are a total of 351 patients with RCC that were recruited between May 1994 and May 2016.

Efficacy of Transosseous Tunnel Placement for Triple Endobutton Plate in Acromioclavicular Joint Reconstruction: A Three-Dimensional Printing Guide Design Technology.

Objective: Explore an accurate transosseous tunnel drilling method based on three-dimensional (3D) printing technology for acromioclavicular joint reconstruction (ACD), design a guide design, and evaluate its accuracy.

Methods: Using Mimics software to reconstruct 100 cases of acromioclavicular joint computed tomography (CT) data. In design 2, the non-collinear tunnel is superimposed on the 3D model, and a virtual drilling is performed between the clavicle and the coracoid using a triple inner gusset.

Antibody prevalence and immunotherapy response in Chinese patients with epilepsy and encephalopathy scores for patients with different neuronal surface antibodies.

Background: The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis. This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy (APE2-CHN) and response to immunotherapy in Chinese patients with epilepsy and encephalopathy (RITE2-CHN) for patients with different neuronal surface antibodies.

Methods: A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital, Capital Medical University, from June 2016 to June 2020 were enrolled in our study.

Viral E Protein Neutralizes BET Protein-Mediated Post-Entry Antagonism of SARS-CoV-2.

Inhibitors of Bromodomain and Extra-terminal domain (BET) proteins are possible anti-SARS-CoV-2 prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here, we show that BET proteins should not be inactivated therapeutically as they are critical antiviral factors at the post-entry level. Knockouts of BRD3 or BRD4 in cells overexpressing ACE2 exacerbate SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection, and not before.

An europium(III) metal-organic framework as a multi-responsive luminescent sensor for highly sensitive and selective detection of 4-nitrophenol and I and Fe ions in water.

A luminescence sensor based on an europium(III)-based lanthanide-organic framework, [Eu(BCB)(DMF)]·(DMF)(HO) (1), was synthesized a solvothermal method using 4,4',4''-benzenetricarbonyltribenzoic acid (HBCB) as a bridging ligand. Single-crystal X-ray diffraction indicates that Eu centers are eight-coordinated with a trigonal dodecahedron and a square antiprismatic configuration, and adjacent Eu atoms are bridged by BCB organic linkers to form a 3D rod-packing structure. Photoluminescence studies show that compound 1 emits bright red luminescence and behaves as a multi-responsive luminescent sensor toward 4-nitrophenol (4-NP) and I and Fe ions in water with high sensitivity, selectivity and low detection limits.

Double deletion of cpxR and tolC significantly increases the susceptibility of Salmonella enterica serovar Typhimurium to colistin.

Background: The increasing use of colistin causes a serious breach in our last line of defence against MDR Gram-negative pathogens. Our previous study showed that CpxR overexpression increases the susceptibility of acrB and cpxR double-deleted Salmonella enterica serovar Typhimurium to colistin.

Objectives: To identify the mechanism of CpxAR and efflux pumps that synergistically enhance the susceptibility of S.

Construction of Core-Shell MOF@COF Hybrids with Controllable Morphology Adjustment of COF Shell as a Novel Platform for Photocatalytic Cascade Reactions.

Recently, novel core-shell MOF@COF hybrids display excellent performance in various fields because of their inherited advantages from their parent MOFs and/or COFs. However, it is still a grand challenge to adjust the morphology of MOFs and/or COFs for consequent performance improvement. Herein, a Ti-MOF@TpTt hybrid coated with ultra-thin COF nanobelt, which is different from the fibrillar-like parent COF, is successfully synthesized through a sequential growth strategy.