The incremental value of left ventricular energy loss in predicting on of adverse events in chronic kidney disease patients with preserved ejection fraction.

BACKGROUND: Vector flow mapping (VFM) is a new echocardiographic technology that can effectively evaluate systolic and diastolic hemodynamic function. However, little is known about the prognostic value of VFM-related parameters. In this paper we aimed to investigate whether left ventricular energy loss (EL) parameters as assessed by VFM enhance prediction of adverse events in patients with chronic kidney disease with preserved ejection fraction. METHODS: One hundred thirty-nine prospectively recruited patients (66% male, 58% on dialysis) with CKD stage 3-5 with normal left ventricular ejection fraction (LVEF) made up the study cohort. Global longitudinal strain (GLS) was calculated using 2-dimensional speckle tracking, and the LV EL during one cardiac cycle for each period was measured using VFM technology. Participants were followed for 4.17 ±â€¯1.58 years for the primary end point of overall mortality and major adverse cardiovascular events (MACE). RESULTS: Forty-five (32%) patients had a primary endpoint event. The EL during each period especially during the ejection stage (Ej-EL) was significantly higher in patients with adverse events than in those without, meanwhile the LV GLS were lower. The Ej-EL (HR: 1.11; 95% CI: 1.06-1.15) and LV GLS (HR: 0.87; 95% CI: 0.81-0.94) (all P < .001) were independent predictors for the primary end point. Increased Ej-EL (≥6.13, 10-3 J/m s) and impaired GLS (<15.52, %) were associated with a higher risk of overall mortality death and MACE (log rank χ2 = 26.94, 7.19; P < .001, =0.007), and DeLong tests showed that Ej-EL (AUC = 0.823) has a slight advantage in predicting adverse events compared to GLS (AUC = 0.681). Furthermore, the addition of Ej-EL to a model with conventional parameters did more to improve the model's discrimination compared to GLS. CONCLUSIONS: Increased Ej-EL as determined by VFM is associated with a higher risk of overall death and MACE in CKD patients with preserved EF.

Asian = machine, Black = animal? The racial asymmetry of dehumanization.

How different racial minorities experience racism differently remains underexplored in existing research. Here, we show that Asian and Black people are often dehumanized differently. Twelve studies spotlight a racial asymmetry in dehumanization using a wide array of methods (experimental, archival, and computational) and data sources (online samples, word embeddings, and U.S. Bureau of Labor Statistics data): Whereas Black people are more often subjected to animalistic dehumanization, Asian people are predominantly subjected to mechanistic dehumanization. We demonstrate this asymmetry from the vantage point of victims (Studies 1a and 1b) and perpetrators (Studies 2a-2d). We further document the prevalence of this asymmetry across diverse domains, from everyday language (Study 3) to perceptions in the realms of romantic relationships (Study 4a), crime rates (Study 4b), and business skills (Study 4c). Finally, we demonstrate the asymmetry's real-world consequences in labor market segregation (Studies 5 and 6). Our findings shed light on the distinct experiences of racism encountered by different racial groups and, more critically, introduce a framework that unifies and integrates scattered empirical observations on perceptions of Asian people. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Change in self-image pressure level before and after autologous fat breast augmentation and its effect on social adaptability.

BACKGROUND: There is an increasingly strong demand for appearance and physical beauty in social life, marriage, and other aspects with the development of society and the improvement of material living standards. An increasing number of people have improved their appearance and physical shape through aesthetic plastic surgery. The female breast plays a significant role in physical beauty, and droopy or atrophied breasts can frequently lead to psychological inferiority and lack of confidence in women. This, in turn, can affect their mental health and quality of life. AIM: To analyze preoperative and postoperative self-image pressure-level changes of autologous fat breast augmentation patients and their impact on social adaptability. METHODS: We selected 160 patients who underwent autologous fat breast augmentation at the First Affiliated Hospital of Xinxiang Medical University from January 2020 to December 2022 using random sampling method. The general information, self-image pressure level, and social adaptability of the patients were investigated using a basic information survey, body image self-assessment scale, and social adaptability scale. The self-image pressure-level changes and their effects on the social adaptability of patients before and after autologous fat breast augmentation were analyzed. RESULTS: We collected 142 valid questionnaires. The single-factor analysis results showed no statistically significant difference in the self-image pressure level and social adaptability score of patients with different ages, marital status, and monthly income. However, there were significant differences in social adaptability among patients with different education levels and employment statuses. The correlation analysis results revealed a significant correlation between the self-image pressure level and social adaptability score before and after surgery. Multiple factors analysis results showed that the degree of concern caused by appearance in self-image pressure, the degree of possible behavioral intervention, the related distress caused by body image, and the influence of body image on social life influenced the social adaptability of autologous fat breast augmentation patients. CONCLUSION: The self-image pressure on autologous fat breast augmentation patients is inversely proportional to their social adaptability.

Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS AND RESULTS: Though analyzing in-depth cardiac macrophage clusters identified by single macrophage RNA-sequencing, we find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages by a dual recombinase-based lineage-tracing approach or selective deletion of macrophage C-C chemokine receptor 2 (CCR2) prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/ATF3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

On the nature of Cu-carbon interaction through N-modification for enhanced ethanol synthesis from syngas and methanol.

Direct conversion of syngas into ethanol is an attractive process because of its short route and high-added value, but remains an enormous challenge due to the low selectivity caused by unclear active sites. Here, the Cu(111) supported N-modified graphene fragments C13-mNm/Cu(111) (m = 0-2) are demonstrated to be an efficient catalyst for fabricating ethanol from syngas and methanol. Our results suggest that the Cu-carbon interaction not only facilitates CO activation, but also significantly affects the adsorption stability of C2 intermediates and finally changes the fundamental reaction mechanism. The impeded hydrogenation performance of C13/Cu(111) due to the introduced Cu-carbon interaction is dramatically improved by N-doping. Multiple analyses reveal that the promoted electron transfer and the enhanced electron endowing ability of C13-mNm/Cu(111) (m = 1-2) to the co-adsorbed CH3CHxOH (x = 0-1) and H are deemed to be mainly responsible for the remarkable enhancement in hydrogenation ability. From the standpoint of the frontier molecular orbital, the decreased HOMO-LUMO gap and the increased overlap extent of HOMO and LUMO with the doping of N atoms also further verify the more facile hydrogenation reactions. Clearly, the Cu-carbon interaction through N-modification is of critical importance in ethanol formation. The final hydrogenation reaction during ethanol formation is deemed to be the rate-controlling step. The insights gained here could shed new light on the nature of Cu-carbon interaction in carbon material modified Cu-based catalysts for ethanol synthesis, which could be extended to design and modify other metal-carbon catalysts.

A red blood cell-derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery.

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy.

Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.

Molecular Dynamics Simulation for the Acidic Compounds Retention Mechanism Study on Octyl-Quaternary Ammonium Mixed-Mode Stationary Phase.

With the widespread application of mixed-mode chromatography in separation analysis, it is becoming increasingly important to study its retention mechanism. The retention behavior of acidic compounds on mixed-mode octyl-quaternary ammonium (Sil-C8-QA) columns was investigated by computer simulation. Firstly, the benzoic acid homologues were used as the analytes, and the simulation model was constructed by the Materials Studio. Geometric optimization, annealing and molecular dynamics (MD) simulation of these complexes resulted in optimized conformations. The binding energy, mean square displacement (MSD) and torsion angle distribution generated by MD simulation were then analyzed. The results showed that the more negative binding energy, the greater the MSD and the narrower the torsion angle distribution, indicating that the stationary phase behaves with stronger interaction and retention. The retention behavior of five acidic drugs on the Sil-C8-QA column was then successfully explained by simulation. Acidic drugs are more retentive on the mixed-mode column due to the more substantial interaction brought by the reversed-phase/ion-exchange mixed-mode mechanism compared to other single-mode columns. This simulation method is expected to provide ideas for studying the separation mechanism and predicting the retention behavior of more complex samples.

Macrophage scavenger receptor-A1 promotes skeletal muscle regeneration after hindlimb ischemia.

Macrophages mediated inflammatory response is crucial for the recovery of skeletal muscle following ischemia. Thus, it's necessary to exploit macrophages based therapeutic targets for ischemic disease. Here, we found mRNA level of SR-A1 was elevated in patients with critical limb ischemia by analysis of gene expression omnibus (GEO) database. Then we investigated the role and the underlined mechanisms of macrophage SR-A1 in a mouse HLI model. Compared with the SR-A1 fl/fl mice, the Lyz Cre/+/SR-A1 flox/flox (SR-A1 ΔMΦ) mice showed significantly lower laser doppler blood flow in the ischemic limb at day 7 after HLI. Consistently, histological analysis exhibited that ischemic limb of SR-A1 ΔMΦ mice displayed more sever and sustained necrotic morphology, inflammation and fibrosis, decreased vessel density and regeneration rate, compared with which of control SR-A1 fl/fl mice. Furthermore, restoration of wild-type myeloid cells to SR-A1 knock-out mice effectively relieved the doppler perfusion in the ischemic limb and restrained skeletal muscle damage 7 days post HLI. In line with in vivo findings, when co-cultivating macrophages with the mouse myoblast line C2C12, SR-A1 -/- bone marrow macrophage significantly inhibited myoblast differentiation in vitro. Mechanically, SR-A1 enhanced skeletal muscle regeneration response to HLI by inhibiting the oncostatin M (OSM) production via suppressed NF-κB signaling activation. These results indicates that SR-A1 is a promising candidate molecule to improve tissue repair and regeneration in peripheral ischemic arterial disease.

Borneol regulates meningeal lymphatic valve plasticity to clear Aß aggregates in the prevention of AD-like symptoms.

BACKGROUND: Meningeal lymphatic vessels (mLVs) have great potential to be the therapeutic target for ß Amyloid protein (Aß) clearing in Alzheimer's disease (AD), but the regulatory methods of the mLVs are limited. The lymphatic valve, marked by FOXC2, is the fundamental structure for maintaining stable lymphatic drainage function. Preliminary evidence suggested that borneol (BO) as the classical phytochemicals could enhance the expression of FOXC2 in the mLVs of healthy mice. PURPOSE: This study aims to explore the regulatory ability of BO on lymphatic valves of mLVs in the AD model mice. STUDY DESIGN: We used the intracerebroventricular injection of Aß42 oligomers to construct the AD-like symptoms model induced by toxic protein deposition. We administered BO nano micelles(BO-Ms) orally before and after to simulate the AD prevention and treatment strategy. METHODS: Herein, this study characterized the efficacy and pathways of BO-Ms for regulating mLVs in AD model by Rt-PCR, WB and confocal microscopy, and determined the effects of BO-Ms on Aß clearance, behavior and safety of AD mice. RESULTS: The AD modeling process severely impaired the expression of lymphatic valves. However, after oral administering BO-Ms for prevention and treatment, an increase in the lymphatic valves of the transverse sinus was observed, which derived from the up-regulation of the transcription factor (FOXC2 and Akt) and the down-regulation of the transcription inhibitors (FOXO1 and PRDM1). Furthermore, the effects of BO-Ms on the lymphatic valves could enhance the lymphatic drainage of the mLVs in AD-like mice, promoting the clearance of toxicity aggregates, protecting neurons, and alleviating AD-like symptoms. Simultaneously, continuous oral BO-Ms for 30 days didn't show any significant organ toxicity. The most important thing was that the preventive effect of BO administration was superior to therapeutic administration in all data. CONCLUSION: In summary, our research indicated that BO is a promoter of lymphatic valve formation in the mLVs, and could prevent or repair damage caused by toxic Aß42. BO was the only bioactive natural product with the ability to regulate mLVs valves. Thus, BO has the potential to become phytochemicals for alleviating AD symptoms by enhancing the drainage function of mLVs.

Disruption of TIGAR-TAK1 alleviates immunopathology in a murine model of sepsis.

Macrophage-orchestrated inflammation contributes to multiple diseases including sepsis. However, the underlying mechanisms remain to be defined clearly. Here, we show that macrophage TP53-induced glycolysis and apoptosis regulator (TIGAR) is up-regulated in murine sepsis models. When myeloid Tigar is ablated, sepsis induced by either lipopolysaccharide treatment or cecal ligation puncture in male mice is attenuated via inflammation inhibition. Mechanistic characterizations indicate that TIGAR directly binds to transforming growth factor ß-activated kinase (TAK1) and promotes tumor necrosis factor receptor-associated factor 6-mediated ubiquitination and auto-phosphorylation of TAK1, in which residues 152-161 of TIGAR constitute crucial motif independent of its phosphatase activity. Interference with the binding of TIGAR to TAK1 by 5Z-7-oxozeaenol exhibits therapeutic effects in male murine model of sepsis. These findings demonstrate a non-canonical function of macrophage TIGAR in promoting inflammation, and confer a potential therapeutic target for sepsis by disruption of TIGAR-TAK1 interaction.

CancerMHL: the database of integrating key DNA methylation, histone modifications and lncRNAs in cancer.

The discovery of key epigenetic modifications in cancer is of great significance for the study of disease biomarkers. Through the mining of epigenetic modification data relevant to cancer, some researches on epigenetic modifications are accumulating. In order to make it easier to integrate the effects of key epigenetic modifications on the related cancers, we established CancerMHL (http://www.positionprediction.cn/), which provide key DNA methylation, histone modifications and lncRNAs as well as the effect of these key epigenetic modifications on gene expression in several cancers. To facilitate data retrieval, CancerMHL offers flexible query options and filters, allowing users to access specific key epigenetic modifications according to their own needs. In addition, based on the epigenetic modification data, three online prediction tools had been offered in CancerMHL for users. CancerMHL will be a useful resource platform for further exploring novel and potential biomarkers and therapeutic targets in cancer. Database URL: http://www.positionprediction.cn/.

Deacylative arylation and alkynylation of unstrained ketones.

Ketones are ubiquitous in bioactive natural products, pharmaceuticals, chemical feedstocks, and synthetic intermediates. Hence, deacylative coupling reactions enable the versatile elaboration of a plethora of chemicals to access complex drug candidates and natural products. Here, we present deacylative arylation and alkynylation strategies for the synthesis of a wide range of alkyl-tethered arenes and alkynes from cyclic ketones and methyl ketones under dual nickel/photoredox catalysis. This reaction begins by generating a pre-aromatic intermediate (PAI) through the condensation of the ketone and N'-methylpicolino-hydrazonamide (MPHA), followed by the oxidative cleavage of the PAI α-C─C bond to form an alkyl radical, which is subsequently intercepted by a Ni complex, facilitating the formation of diverse C(sp3)-C(sp2)/C(sp) bonds with remarkable generality. This protocol features a one-pot reaction capability, high regioselectivity and ring-opening efficiency, mild reaction conditions, and a broad substrate scope with excellent functional group compatibility.

Epidemiologic analysis of antimicrobial resistance in hospital departments in China from 2022 to 2023.

Bacterial drug resistance monitoring in hospitals is a crucial aspect of healthcare management and a growing concern worldwide. In this study, we analysed the bacterial drug resistance surveillance in our hospital from 2022 Q1 to 2023 Q2. The main sampling sources were respiratory, blood, and urine-based, and the main clinical infections were respiratory and genitourinary in nature. Specimens were inoculated and cultured; bacterial strains were isolated using a VITEK® 2 Compact 60-card automatic microorganism identifier (bioMerieux, Paris, France) and their matching identification cards were identified, and manual tests were supplemented for strain identification. The most common Gram-positive bacteria detected were Staphylococcus aureus, followed by Enterococcus faecalis (E. faecalis), Staphylococcus epidermidis (S. epidermidis), and Staphylococcus haemolyticus (S. haemolyticus). The most common Gram-negative bacteria detected were Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most prevalent multidrug-resistant bacteria were those producing extended-spectrum beta-lactamases, followed by methicillin-resistant Staphylococcus aureus, followed by carbapenem-resistant Enterobacterales. This study suggests that the prevention and control of infections in the respiratory and genitourinary systems should be the focus of anti-infective work and that the use of antimicrobials should be reduced and regulated to prevent the emergence and spread of resistant bacteria.

Anti-UV Microgel Based on Interfacial Polymerization to Decrease Skin Irritation of High Permeability UV Absorber Ethylhexyl Methoxycinnamate.

Ethylhexyl methoxycinnamate (EHMC) is frequently employed as a photoprotective agent in sunscreen formulations. EHMC has been found to potentially contribute to health complications as a result of its propensity to produce irritation and permeate the skin. A microgel carrier, consisting of poly(ethylene glycol dimethacrylate) (pEDGMA), was synthesized using interfacial polymerization with the aim of reducing the irritation and penetration of EHMC. The thermogravimetric analysis (TGA) indicated that the EHMC content accounted for 75.72% of the total composition. Additionally, the scanning electron microscopy (SEM) images depicted the microgel as exhibiting a spherical morphology. In this study, the loading of EHMC was demonstrated through FTIR and contact angle tests. The UV resistance, penetration, and skin irritation of the EHMC-pEDGMA microgel were additionally assessed. The investigation revealed that the novel sunscreen compound, characterized by limited dermal absorption, had no irritant effects and offered sufficient protection against ultraviolet radiation.

CoAl-LDH decorated with cerium oxide as an efficient adsorbent for restoring low-concentration phosphate in wastewater.

The requirement for the removal of phosphorus (P) from wastewater has become progressively stringent, therefore, it is essential to remove low-concentration phosphate from secondary effluents through a tertiary treatment. One of the biggest challenges in removing phosphate from wastewater is the development of low-cost, green, and pollution-free adsorbents. In this study, novel, eco-friendly and low-cost CeO2 nanosphere modifying CoAl-LDH nanosheets (CoAl-LDH/CeO2) were successfully fabricated using a classical hydrothermal strategy. The microstructure and morphology of CoAl LDH/CeO2 were characterized using SEM, TEM, FTIR, XRD, TG, XPS, and BET techniques. The performance of the P adsorption from water for CoAl-LDH/CeO2 was investigated. The influences of adsorption parameters, such as adsorbent dosage, pH, phosphate concentration, adsorption time, and experimental temperature, were investigated through batch adsorption experiments. The batch adsorption experiments showed that the P removal by CoAl-LDH/CeO2 could reach 93.4% at room temperature within 60 minutes. CoAl-LDH/CeO2 showed ultrafast and high-efficiency adsorption for low concentration P contaminated wastewater. Pseudo-second order model exhibited better fitting with the kinetics of the phosphate adsorption, while the Freundlich model well-described the isotherm results (R2 > 0.999). Although Cl-, NO3-and SO42- coexisted in the solution, CoAl-LDH/CeO2 still possessed favourable selectivity for phosphates. More importantly, the adsorption capacities of CoAl-LDH/CeO2 retained over 85% after five cycles. Therefore, the low cost and sustainable utilization of CoAl-LDH/CeO2 for the phosphate removal from secondary effluent with phosphate at a low concentration highlights its potential application to alleviate eutrophication.

Electrically Triggered Domain Wall Movement in Cu2Se Semiconductor.

The ion-conductive α-Cu2Se is found to possess antipolar dipoles, and the movement of the domain boundary under the applied voltage causes change of resistance, showing promising application in memristors. However, due to the complex ordering of Cu ions in the α-Cu2Se, there are multiple types of domain wall structure. Here, we show that two typical domain walls in α-Cu2Se can be formed, by controlling the voltage during phase transition from high-temperature cubic ß-Cu2Se to α-Cu2Se. We also show by in situ transmission electron microscopy that the formed [01̅0]/[101̅] domain wall performs a reversible movement under the applied external voltage, while the [010]/[01̅0] domain wall does not move. We further demonstrate that pinning of the [010]/[01̅0] domain wall could be due to the formed dislocations in the interface. This study shows that applying preprocess conditions is important to obtain the designed microstructure and resistive properties of α-Cu2Se.

Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia.

Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potency in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.

Coregulatory effects of multiple histone modifications in key ferroptosis-related genes for lung adenocarcinoma.

Aim: The present study was designed to investigate the coregulatory effects of multiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). Materials & methods: Ten histones for LUAD were analyzed using ChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expression to identify strong coregulatory genes and regions. This method was applied to explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. Results: Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (CA9, PGD, CDKN2A, PML, OTUB1 and NFE2L2). Conclusion: This quantitative method could be used to identify important HM coregulatory genes and regions that may be epigenetic regulatory targets in cancers.