Adjusting methylation levels with nucleus proportions highlights functional significance of differentially methylated cytosines associated with pre-eclampsia.

Studies on DNA methylation alterations associated with pre-eclampsia (PE) have improved our understanding of the mechanisms underlying this disorder. However, differentially methylated cytosines (DMCs) have not been adjusted for cell-type heterogeneity, hampering the identification of alterations that drive disease risk. Using a reference-based, cell-type deconvolution approach, we estimated the nuclear proportions of 335 placental samples based on DNA methylation data.

Recent Advances in Nanoimmunotherapy by Modulating Tumor-Associated Macrophages for Cancer Therapy.

Cancer immunotherapy has yielded remarkable results across a variety of tumor types. Nevertheless, the complex and immunosuppressive microenvironment within solid tumors poses significant challenges to established therapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T-cell (CAR-T) therapy. Within the milieu, tumor-associated macrophages (TAMs) play a significant role by directly suppressing T-cell functionality and fostering an immunosuppressive environment.

Toward Heisenberg scaling in non-Hermitian metrology at the quantum regime.

Non-Hermitian quantum metrology, an emerging field at the intersection of quantum estimation and non-Hermitian physics, holds promise for revolutionizing precision measurement. Here, we present a comprehensive investigation of non-Hermitian quantum parameter estimation in the quantum regime, with a special focus on achieving Heisenberg scaling. We introduce a concise expression for the quantum Fisher information (QFI) that applies to general non-Hermitian Hamiltonians, enabling the analysis of estimation precision in these systems.

GSH/pH dual responsive chitosan nanoparticles for reprogramming M2 macrophages and overcoming cancer chemoresistance.

The combination of two or more drugs with different mechanisms of action is a promising strategy for circumventing multidrug resistance (MDR). However, the antitumor effect of nanosystems is usually limited due to the simultaneous release of different payloads at a single location rather than at their respective sites of action. Herein, we report a GSH and pH dual responsive nanoplatform encapsulated with doxorubicin (DOX) and resiquimod (R848) (GPNP) for combinatorial chemotherapy against cancer cells with drug resistance.

Placental ischemia disrupts DNA methylation patterns in distal regulatory regions in rats.

Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality worldwide. However, the impact of PE on the organization of the functional architecture of the placental methylome remains largely unknown. We performed whole-genome bisulfite sequencing of placental DNA and applied a Hidden Markov Model to investigate epigenome-wide alterations in functional structures, including partially methylated domains (PMDs), low-methylated regions (LMRs), and unmethylated regions (UMRs), in a reduced uterine perfusion pressure (RUPP) rat model of PE.

Recent Advances in Supramolecular-Macrocycle-Based Nanomaterials in Cancer Treatment.

Cancer is a severe threat to human life. Recently, various therapeutic strategies, such as chemotherapy, photodynamic therapy, and combination therapy have been extensively applied in cancer treatment. However, the clinical benefits of these therapeutics still need improvement.

Targeted bisulfite resequencing of differentially methylated cytosines in pre-eclampsia reveals a skewed dynamic balance in the DNA methylation of enhancers.

Pre-eclampsia (PE) is a major hypertensive disorder of pregnancy. Widespread differentially methylated cytosines (DMCs) with modest changes in methylation level are associated with PE, whereas their cause and biological significance remain unknown. We aimed to clarify DNA methylation patterns around DMCs in 103 placentas using MethylCap targeted bisulfite re-sequencing (MethylCap-seq) assays of 690 selected DMCs.

Calixarene-modified albumin for stoichiometric delivery of multiple drugs in combination-chemotherapy.

In combination chemotherapy, the molar ratio of drugs is a critical parameter that determines the synergistic effects. However, most co-delivery vectors are incapable of maintaining the optimal molar ratio of drugs throughout the delivery process. Herein, a calixarene-modified albumin (CaMA), which can co-deliver multiple drugs with precise control of the drug ratio, is presented.

Sperm epigenetic alterations contribute to inter- and transgenerational effects of paternal exposure to long-term psychological stress via evading offspring embryonic reprogramming.

Paternal life experiences impact offspring health via germline, and epigenetic inheritance provides a potential mechanism. However, global reprogramming during offspring embryogenesis and gametogenesis represents the largest hurdle to conceptualize it. Yet, detailed characterization of how sperm epigenetic alterations carrying "environmental memory" can evade offspring embryonic reprogramming remains elusive.

Multistage Adaptive Nanoparticle Overcomes Biological Barriers for Effective Chemotherapy.

Drug delivery systems (DDS) are extensively studied to improve the solubility, stability, pharmacokinetic, and biodistribution of chemotherapeutics. However, the drug delivery efficiency of traditional DDS is often limited by the complicated biological barriers in vivo. Herein, a multistage adaptive nanoparticle (MAN) that simultaneously overcomes multiple biological barriers to achieve tumor-targeted drug delivery with high efficiency is presented.

A near-infrared light-excitable immunomodulating nano-photosensitizer for effective photoimmunotherapy.

Photodynamic therapy has great potential for tumor ablation and the activation of antitumor immune responses. However, its overall therapeutic efficiency is often limited by the immunosuppressive tumor microenvironment. We developed a near-infrared light-excitable immunomodulating nano-photosensitizer (NeINP) that can improve reactive oxygen species production and regulate the immunosuppressive TME to improve photoimmunotherapy.

Virus-like nanoparticle as a co-delivery system to enhance efficacy of CRISPR/Cas9-based cancer immunotherapy.

The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9) system holds great promise for the cancer gene therapy. However, due to complicated signal networks and various compensatory mechanisms in tumors, adjusting a single molecular pathway has limited effects on cancer treatments. Herein, a virus-like nanoparticle (VLN) was reported as a versatile nanoplatform to co-deliver CRISPR/Cas9 system and small molecule drugs for effective malignant cancer treatment.

Multifunctional Nanomodulators Regulate Multiple Pathways To Enhance Antitumor Immunity.

Immunosuppression is a key factor leading to a low therapeutic efficiency of the currently used immunotherapies. Monotherapies are unable to overcome immunosuppression because of the complex interplay of immune cells in tumors. Herein, we report a multifunctional nanomodulator (MFNM) as a carrier to deliver different types of immune modulators for comodulating multiple pathways.

Genetic regulatory subnetworks and key regulating genes in rat hippocampus perturbed by prenatal malnutrition: implications for major brain disorders.

Objective: Many population studies have shown that maternal prenatal nutrition deficiency may increase the risk of neurodevelopmental disorders in their offspring, but its potential transcriptomic effects on brain development are not clear. We aimed to investigate the transcriptional regulatory interactions between genes in particular pathways responding to the prenatal nutritional deficiency and to explore their effects on neurodevelopment and related disorders.

Results: We identified three modules in rat hippocampus responding to maternal prenatal nutritional deficiency and found 15 key genes () related to the rat hippocampus developmental dysregulation, of which and related to autism, and and are related to Alzheimer's disease, and schizophrenia.

Dual-Locking Nanoparticles Disrupt the PD-1/PD-L1 Pathway for Efficient Cancer Immunotherapy.

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) enzyme, Cas13a, holds great promise in cancer treatment due to its potential for selective destruction of tumor cells via collateral effects after target recognition. However, these collateral effects do not specifically target tumor cells and may cause safety issues when administered systemically. Herein, a dual-locking nanoparticle (DLNP) that can restrict CRISPR/Cas13a activation to tumor tissues is described.

Co-expression network analysis identified hub genes critical to triglyceride and free fatty acid metabolism as key regulators of age-related vascular dysfunction in mice.

Aging has often been linked to age-related vascular disorders. The elucidation of the putative genes and pathways underlying vascular aging likely provides useful insights into vascular diseases at advanced ages. Transcriptional regulatory network analysis is the key to describing genetic interactions between molecular regulators and their target gene transcriptionally changed during vascular aging.

Metabolomic profiling on rat brain of prenatal malnutrition: implicated for oxidative stress and schizophrenia.

Schizophrenia is a kind of neurodevelopmental disease. Epidemiological data associates schizophrenia with prenatal exposure to famine. Relevant prenatal protein deprivation (PPD) rodent models support this result by observing decreasing prepulse inhibition, altered hippocampal morphology and impaired memory in offspring.

In Situ Modification of the Tumor Cell Surface with Immunomodulating Nanoparticles for Effective Suppression of Tumor Growth in Mice.

Current cancer immunotherapies including chimeric antigen receptor (CAR)-based therapies and checkpoint immune inhibitors have demonstrated significant clinical success, but always suffer from immunotoxicity and autoimmune disease. Recently, nanomaterial-based immunotherapies are developed to precisely control in vivo immune activation in tumor tissues for reducing immune-related adverse events. However, little consideration has been put on the spatial modulation of interactions between immune cells and cancer cells to optimize the efficacy of cancer immunotherapies.

Epigenome-wide association data implicate fetal/maternal adaptations contributing to clinical outcomes in preeclampsia.

To investigate the changes of placental DNA methylome in preeclampsia (PE). We performed an epigenome-wide association study in a Chinese cohort and six published datasets consisting of 335 samples in total. Numerous consistently hypomethylated probes were associated with early-onset PE in different populations, with 2125 reaching epigenome-wide significance.

Opioid Exposure is Associated with Aberrant DNA Methylation of OPRM1 Promoter Region in a Chinese Han Population.

The μ-opioid receptor (OPRM1) plays an important role in opiate addiction. The OPRM1 gene promoter showed hypermethylation in lymphocytes of opiate addicts as well as opioid medications users, while the methylation status displayed ethnic diversity. The purpose of the study was to investigate the methylation pattern of OPRM1 promoter in the Han Chinese population.

Effects of early-life malnutrition on neurodevelopment and neuropsychiatric disorders and the potential mechanisms.

Lines of evidence have demonstrated that early-life malnutrition is highly correlated with neurodevelopment and adulthood neuropsychiatric disorders, while some findings are conflicting with each other. In addition, the biological mechanisms are less investigated. We systematically reviewed the evidence linking early-life nutrition status with neurodevelopment and clinical observations in human and animal models.

The DNA methylation status of genes encoding Matrix metalloproteinases and tissue inhibitors of Matrix metalloproteinases in endometriosis.

Endometriosis is a benign disease, with malignant properties. A necessary step in the progression of endometriosis is tissue remodeling, which is coordinated by the activities of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). This study evaluated the regulation of abnormal MMP and TIMP gene expression during endometriosis.