dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection.

Background: Tandem repeats (TRs) are abundant in the human genome and associated with repeat expansion disorders. Our study aimed to develop a tandem repeat panel utilizing targeted long-read sequencing to evaluate known TRs associated with these disorders and assess its clinical utility.

Methods: We developed a targeted long-read sequencing panel for 70 TR loci, termed dynamic mutation third-generation sequencing (dmTGS), using the PacBio Sequel II platform.

Pentafluorosulfanylation of Acrylamides: The Synthesis of SF-Containing Isoquinolinediones with SFCl.

We disclose herein an efficient and facile method for the synthesis of SF-containing isoquinolinediones with an all-carbon quaternary stereocenter via intramolecular pentafluorosulfanylation of acrylamides using SFCl as a pentafluorosulfanylation reagent. The protocol proceeds under mild reaction conditions and enjoys a broad substrate scope, wide functional group compatibility, and high atom- and step-economy. A radical mechanism involving the SF radical cascade addition/cyclization of acrylamides is proposed.

Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score).

The insensitivity of sleep to an unfamiliar sleeping environment in patients with insomnia disorder.

Background: Sleeping in an unfamiliar environment, such as a sleep laboratory, is thought to disturb sleep in healthy individuals and could express a hyperarousal state called the first night effect. Insomnia disorder (ID) is a highly prevalent health problem characterized by increased arousal during the night and daytime. Whether or not a similar phenomenon occurs in patients with ID is unclear.

Thalamic network under wakefulness after sleep onset and its coupling with daytime fatigue in insomnia disorder: An EEG-fMRI study.

Background: Fatigue is the most common daytime impairment of insomnia disorder (ID). Thalamus is acknowledged as the key brain region closely associated with fatigue. However, the thalamus-based neurobiological mechanisms of fatigue in patients with ID remain unknown.

Differential proteomic patterns of plasma extracellular vesicles show potential to discriminate β-thalassemia subtypes.

The observed specificity of β-thalassemia-subtype phenotypes makes new diagnostic strategies that complement current screening methods necessary to determine each subtype and facilitate therapeutic regimens for different patients. Here, we performed quantitative proteomics of plasma-derived extracellular vesicles (EVs) of β-thalassemia major (TM) patients, β-thalassemia intermedia (TI) patients, and healthy controls to explore subgroup characteristics and potential biomarkers. Plasma quantitative proteomics among the same cohorts were analyzed in parallel to compare the biomarker potential of both specimens.

Increased connectivity of the anterior cingulate cortex is associated with the tendency to awakening during N2 sleep in patients with insomnia disorder.

Study Objectives: To investigate the relationship between sleep transition dynamics and stage-specific functional connectivity (FC) of the anterior cingulate cortex (ACC) in patients with insomnia disorder (ID).

Methods: Simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) data from 37 patients with ID and 30 well-matched healthy controls (HCs) were recorded during wakefulness and different sleep stages and subsequently analyzed. A Markov chain model was used to estimate the transition probability between each stage.

Immune cell profiling of preeclamptic pregnant and postpartum women by single-cell RNA sequencing.

Preeclampsia (PE), a leading cause of maternal and fetal morbidity and mortality, is closely related to the immune system alterations. However, little is known about the landscape and heterogeneity of maternal immune system at single-cell level among PE patients. In this study, peripheral blood mononuclear cells (PBMCs) were isolated from three early-onset preeclamptic pregnant women and two healthy control, respectively.

Sleep discrepancy is associated with alterations in the salience network in patients with insomnia disorder: An EEG-fMRI study.

Background: Positron emission tomography - computed tomography (PET-CT) research has shown that sleep discrepancy recorded by self-report and polysomnography (PSG) may be related to the altered metabolic rate of the anterior insula (aINS) during non-rapid eye movement (NREM) sleep in patients with insomnia disorder. We aim to explore the functional connectivity of aINS across wake and NREM sleep in the patients and to reveal the association between aINS connectivity and sleep discrepancy.

Methods: Patients with insomnia disorder (n = 33) and healthy controls (n = 31) underwent simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) during nighttime sleep, and aINS-based connectivity was calculated across wake and NREM sleep.

The PTS-KdpDE-KdpFABC Pathway Contributes to Low Potassium Stress Adaptation and Competitive Nodulation of Sinorhizobium fredii.

The rhizobium-legume symbiosis is essential for sustainable agriculture by reducing nitrogen fertilizer input, but its efficiency varies under fluctuating soil conditions and resources. The nitrogen-related phosphotransferase system (PTS) consisting of PtsP, PtsO, and PtsN is required for optimal nodulation and nitrogen fixation efficiency of the broad-host-range Sinorhizobium fredii CCBAU45436 associated with diverse legumes, though the underlying mechanisms remain elusive. This work characterizes the PtsN-KdpDE-KdpFABC pathway that contributes to low potassium adaptation and competitive nodulation of CCBAU45436.

Effect of Probiotics Supplementation on Heart Rate: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background And Aims: Probiotics consumption lowers the risk of cardiovascular disease, but whether it affects heart rate (HR) remains controversial. Therefore, our study aimed to assess the chronotropic effects of probiotics on heartbeat via a meta-analysis of randomized clinical trials.

Methods: Relevant studies were identified by searching PubMed, Cochrane library, and Clinical Trials databases up to October 2021.

Whole exome sequencing is an alternative method in the diagnosis of mitochondrial DNA diseases.

Background: Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)-based testing as an alternative option for the diagnosis of MD.

Oat Fiber Modulates Hepatic Circadian Clock via Promoting Gut Microbiota-Derived Short Chain Fatty Acids.

The biological alteration of circadian rhythm was found to be related to the development of metabolic disorders. Our previous studies reported that impaired lipid metabolism caused by a high-fat diet was improved by oat fiber, but did not attempt to answer whether the improvement is mechanistically linked to circadian rhythm. By focusing on circadian alteration, the present study aimed to elucidate the effect of gut microbiota-derived short chain fatty acids (SCFAs) on circadian rhythm in a high-fat diet experimental paradigm with and without dietary oat fiber feeding.

Spindle-related brain activation in patients with insomnia disorder: An EEG-fMRI study.

Sleep spindles have been implicated in sleep protection, depression and anxiety. However, spindle-related brain imaging mechanism underpinning the deficient sleep protection and emotional regulation in insomnia disorder (ID) remains elusive. The aim of the current study is to investigate the relationship between spindle-related brain activations and sleep quality, symptoms of depression and anxiety in patients with ID.

A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA).

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both α and β thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests.

Design, Synthesis, and Evaluation of -(Biphenyl-3-ylmethoxy)nitrophenyl Derivatives as PD-1/PD-L1 Inhibitors with Potent Anticancer Efficacy .

Two series of novel -(biphenyl-3-ylmethoxy)nitrophenyl compounds ( and ) were designed as programmed cell death protein 1 (PD-1)/PD-ligand 1 (PD-L1) inhibitors. All compounds showed significant inhibitory activity with IC values ranging from 2.7 to 87.

Effects of Oat Fiber Intervention on Cognitive Behavior in LDLR Mice Modeling Atherosclerosis by Targeting the Microbiome-Gut-Brain Axis.

It is known that cardiovascular disease can result in cognitive impairment. However, whether oat fiber improves cognitive behavior through a cardiovascular-related mechanism remains unclear. The present work was aimed to elucidate the potential of oat fiber on cognitive behavior by targeting the neuroinflammation signal and microbiome-gut-brain axis in a mouse model of atherosclerosis.

Reduced neuropathy target esterase in pre-eclampsia suppresses tube formation of HUVECs via dysregulation of phospholipid metabolism.

Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs).

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear.

The influence of placebo administration on the first- night effect in patients with insomnia disorder.

Objective: We aimed to investigate the effects of placebo on the first-night effect (FNE) in insomniacs.

Methods: In sum, 36 patients with insomnia disorder who met the DSM-5 criteria were enrolled in this study. Sixteen patients with insomnia disorder were given two days of placebo intervention (placebo-administration group, PL).

Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects .

Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds , and exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1.