Plasma protein binding of arsenic species in acute promyelocytic leukemia patients and their relationships with hepatic and renal function.

OBJECTIVES: Percentage protein binding (%PB) of arsenic species in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide remains unclear. It can be different depending on the status of hepatic or renal function. METHODS: This study obtained steady-state blood samples from normal APL patients and those with hepatic or renal impairment. %PB of inorganic arsenic (iAs), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) was determined by analyzing free and total plasma concentrations using ultrafiltration method by HPLC-HG-AFS. RESULTS: There is a linear relationship between free and total plasma concentrations for iAs (r2 = 0.952), MMAV (r2 = 0.603), and DMAV (r2 = 0.945). For patients with normal hepatic and renal function, mean %PB was as follows: iAs at 26.7 ± 14.3%, MMAV at 53.3 ± 11.9%, and DMAV at 24.7 ± 7.8%. %PB decreased in patients with renal impairment, with MMAV and DMAV showing statistically significant differences (p < 0.05 for MMAV, p < 0.01 for DMAV). No significant differences in %PB between normal and hepatic impairment group were observed. CONCLUSION: Free arsenic species fraction can be estimated by total concentration. DMAV and iAs present low %PB, while MMAV exhibits a relatively high %PB in plasma. Level of %PB is more likely to be affected by renal function and age.

Angiotensin-(1-7) relieves behavioral defects and α-synuclein expression through NEAT1/miR-153-3p axis in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, whose characteristic pathology involves progressive deficiency of dopaminergic neurons and generation of Lewy bodies (LBs). Aggregated and misfolded α-synuclein (α-syn) is the major constituent of LBs. As the newly discovered pathway of renin-angiotensin system (RAS), Angiotensin-(1-7) (Ang-(1-7)) and receptor Mas have attracted increasing attentions for their correlation with PD, but underlying mechanisms remain not fully clear. Based on above, this study established PD models of mice and primary dopaminergic neurons with AAV-hα-syn(A53T), then discussed the effects of Ang-(1-7)/Mas on α-syn level and neuronal apoptosis for these models combined with downstream long non-coding RNA (lncRNA) and microRNA (miRNA). Results showed that Ang-(1-7) alleviated behavioral impairments, rescued dopaminergic neurons loss and lowered α-syn expression in substantia nigra of hα-syn(A53T) overexpressed PD mice. We also discovered that Ang-(1-7) decreased level of α-syn and apoptosis in the hα-syn(A53T) overexpressed dopaminergic neurons through lncRNA NEAT1/miR-153-3p axis. Moreover, miR-153-3p level in peripheral blood is found negatively correlated with that of α-syn. In conclusion, our work not only showed neuroprotective effect and underlying mechanisms for Ang-(1-7) on α-syn in vivo and vitro, but also brought new hope on miR-153-3p and NEAT1 for diagnosis and treatment in PD.

Comparing Insulin Against Glucagon-Like Peptide-1 Receptor Agonists, Dipeptidyl Peptidase-4 Inhibitors, and Sodium-Glucose Cotransporter 2 Inhibitors on 5-Year Incident Heart Failure Risk for Patients With Type 2 Diabetes Mellitus: Real-World Evidence Study Using Insurance Claims.

Background: Type 2 diabetes mellitus (T2DM) is a common health issue, with heart failure (HF) being a common and lethal long-term complication. Although insulin is widely used for the treatment of T2DM, evidence regarding the efficacy of insulin compared to noninsulin therapies on incident HF risk is missing among randomized controlled trials. Real-world evidence on insulin's effect on long-term HF risk may supplement existing guidelines on the management of T2DM. Objective: This study aimed to compare insulin therapy against other medications on HF risk among patients with T2DM using real-world data extracted from insurance claims. Methods: A retrospective, observational study was conducted based on insurance claims data from a single health care network. The study period was from January 1, 2016, to August 11, 2021. The cohort was defined as patients having a T2DM diagnosis code. The inclusion criteria were patients who had at least 1 record of a glycated hemoglobin laboratory test result; full insurance for at least 1 year (either commercial or Medicare Part D); and received glucose-lowering therapy belonging to 1 of the following groups: insulin, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4Is), or sodium-glucose cotransporter-2 inhibitors (SGLT2Is). The main outcome was the 5-year incident HF rate. Baseline covariates, including demographic characteristics, comorbidities, and laboratory test results, were adjusted to correct for confounding. Results: After adjusting for a broad list of confounders, patients receiving insulin were found to be associated with an 11.8% (95% CI 11.0%-12.7%), 12.0% (95% CI 11.5%-12.4%), and 15.1% (95% CI 14.3%-16.0%) higher 5-year HF rate compared to those using GLP-1 RAs, DPP-4Is, and SGLT2Is, respectively. Subgroup analysis showed that insulin's effect of a higher HF rate was significant in the subgroup with high HF risk but not significant in the subgroup with low HF risk. Conclusions: This study generated real-world evidence on the association of insulin therapy with a higher 5-year HF rate compared to GLP-1 RAs, DPP-4Is, and SGLT2Is based on insurance claims data. These findings also demonstrated the value of real-world data for comparative effectiveness studies to complement established guidelines. On the other hand, the study shares the common limitations of observational studies. Even though high-dimensional confounders are adjusted, remaining confounding may exist and induce bias in the analysis.

Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression.

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.

Dominant and genome-wide formation of DNA:RNA hybrid G-quadruplexes in living yeast cells.

Guanine-rich DNA forms G-quadruplexes (G4s) that play a critical role in essential cellular processes. Previous studies have mostly focused on intramolecular G4s composed of four consecutive guanine tracts (G-tracts) from a single strand. However, this structural form has not been strictly confirmed in the genome of living eukaryotic cells. Here, we report the formation of hybrid G4s (hG4s), consisting of G-tracts from both DNA and RNA, in the genome of living yeast cells. Analysis of Okazaki fragment syntheses and two other independent G4-specific detections reveal that hG4s can efficiently form with as few as a single DNA guanine-guanine (GG) tract due to the participation of G-tracts from RNA. This finding increases the number of potential G4-forming sites in the yeast genome from 38 to 587,694, a more than 15,000-fold increase. Interestingly, hG4s readily form and even dominate at G4 sites that are theoretically capable of forming the intramolecular DNA G4s (dG4s) by themselves. Compared to dG4s, hG4s exhibit broader kinetics, higher prevalence, and greater structural diversity and stability. Most importantly, hG4 formation is tightly coupled to transcription through the involvement of RNA, allowing it to function in a transcription-dependent manner. Overall, our study establishes hG4s as the overwhelmingly dominant G4 species in the yeast genome and emphasizes a renewal of the current perception of the structural form, formation mechanism, prevalence, and functional role of G4s in eukaryotic genomes. It also establishes a sensitive and currently the only method for detecting the structural form of G4s in living cells.

The development of hooded awns in barley: From ectopic Kap1 expression to yield potential.

Awns in barley have different shapes including awnless, straight, hooded, crooked, and leafy awns. The hooded awns are characterized by an appendage of the lemma, which forms a trigonal or cap-shaped structure, and even blossoms and yields fruits on barley awn. In the lemma primordia of wild-type (straight awn), cells divide and elongate to form the straight awn. However, in the lemma primordia of KNOX3 mutant (hooded awn), cells divide at various orientations without elongating, and they form hooded awns. This phenomenon is due to the upregulation of KNOX3 expression via insertion of a tandem direct duplication of 305 bp in the intron IV. Here, we summarize the development of barley hooded awn research in the following two aspects: on the one hand, the morphology, development of hooded awns, and the expression regulation of the KNOX3 gene. The latter includes ectopic expression of the KNOX3 gene, gene interactions among awn-related genes, the regulatory relationship between class I KNOX genes and hormones, as well as the influence of abiotic stresses. On the other hand, the potential performance of hooded awns in barley for yield breeding is discussed. Hooded awns have potential application value in forage, which could compensate for the disadvantage of the long straight awn in the barley straw used for feed in modern cultivars. In addition, the hooded awn produces ectopic meristems to develop complete florets, which is an interesting question and helps to understand the development, adaptation, and evolution of plant floral organs.

Trimethylamine N-Oxide Aggravates Neuro-Inflammation via lncRNA Fendrr/miR-145-5p/PXN Axis in Vascular Dementia Rats.

Purpose: Vascular dementia (VaD) is the second most common dementia in the world. An increasing number of studies have demonstrated the important role of long non-coding RNAs (lncRNAs) in VaD. Our previous investigation demonstrated that Trimethylamine-N-oxide (TMAO) exacerbates cognitive impairment and neuropathological alterations in VaD rats. Thus, we hypothesized that TMAO could play an injury role in VaD by regulating lncRNAs. Materials and Methods: The rats using the bilateral common carotid artery (2VO) model were administered TMAO (120 mg/kg) for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was conducted to investigate the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was performed to identify potential downstream targets. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of lncRNA fetal-lethal noncoding developmental regulatory RNA (Fendrr), miR-145-5p, and paxillin (PXN). Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. Furthermore, we used the Fendrr loss-of-function assay, miR-145-5p gain-of-function assays and PXN loss-of-function assay to explore the mechanisms by which TMAO acts on VaD. Results: TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr exhibits highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats. Conclusion: The results of this study indicated that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of VaD.

Segmented propagation model for the paths and travel times of surface duct leaky signals.

In the deep ocean environment with a surface duct, sound propagating within the duct leaks into the geometric shadow zone below it. However, the propagation paths and time of these leaky parts have not been fully characterized. This paper investigates the mechanism of surface duct leaky (SDL) signals based on normal mode theory. It reveals that SDL signals are caused by specific modes with grazing angles close to zero at the bottom of the surface duct. Combining the theory of diffracted sound rays, the study proposes a Segmented Propagation model (SPM) for SDL signals. The propagation paths of SDL signals are divided into three segments: S1, which extends from the source to the surface duct; S2, the segment propagating within the surface duct; and S3, the segment leading from the surface duct to the receiver. The proposed SPM describes the propagation mechanism of SDL signals and allows for precise calculation of their propagation time. Experimental data from the western Pacific are used to verify the SPM.

Acute aconitine poisoning resulting from the ingestion of medicinal liquor.

Diester diterpenoid alkaloids (DDAs) are the main active ingredients of herbaceous perennial plants Aconitum. DDAs possess cardiotoxic and neurotoxic properties. Although most deaths caused by DDA poisoning are accidental, a few instances of suicide and homicide have been reported. Presented is a case of an acute aconitine (AC) poisoning following the ingestion of approximately 50 mL of homemade medicinal liquor. We described the clinical manifestations after poisoning and detailed postmortem changes, and detected the concentrations of AC and hypaconitine (HA) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The decedent experienced a burning sensation in the gastrointestinal tract after poisoning, followed by flushing and paralysis of the face and limbs, and severe cardiac arrhythmia. An autopsy revealed cyanosis of the lips and nail beds; conjunctival hemorrhage in both eyes; pulmonary edema; tissue hemorrhage and congestion in multiple organs; and inflammatory cell infiltration in the stomach, duodenum, pancreas, and cardiac muscle. The concentrations of AC and HA were as follows: cardiac blood, 38.4 ng/mL and 7.1 ng/mL; pericardial fluid, 7.3 ng/mL and 41 ng/mL; urine, 28.1 ng/mL and 574 ng/mL; bile, 38.5 ng/mL and 108 ng/mL; gastric contents, 0.06 mg and 0.56 mg; liver tissue, 10.7 ng/g and 109.6 ng/g; and medicinal liquor, 0.568 mg/mL and 0.664 mg/mL, respectively. The clinical manifestations, anatomy findings, and quantitative data on the concentrations of AC and HA in body fluids and tissues will aid forensic investigations of deaths caused by acute AC poisoning.

Extended Surface Bands Enabled Lasing Emission and Wavelength Switch from Sulfur Quantum Dots.

The development of a lasing wavelength switch, particularly from a single inorganic gain material, is challenging but highly demanded for advanced photonics. Nonetheless, all current lasing emission of inorganic gain materials arises from band-edge states, and the inherent fixed bandgap limitation of the band-edge system leads to the inaccessibility of lasing wavelength switching from a single inorganic gain material. Here the realization of a single inorganic gain material-based lasing wavelength switch is reported by proposing an alternative lasing emission strategy, that is, lasing emission from surface gain. Previous efforts to achieve surface-gain-enabled lasing emission have been hindered by the limited gain volume provided by surface states due to the broad emission bandwidth and/or low emission efficiency. This challenge is overcome by introducing extended surface bands onto the surface of sulfur quantum dots. The extended surface bands contribute to a high photoluminescence quantum yield and narrow emission bandwidth, thereby providing sufficient gain volume and facilitating stimulated emission. When combined with whispering gallery mode microcavity, surface gain enabled lasing emission manifests an ultralow threshold of 8.3 µJ cm-2. Remarkably, the reconfigurable perturbation to surface gain, facilitated by molecular affinity, allows for the realization of the lasing wavelength switch from a single inorganic gain material.

COL6A6 Peptide Vaccine Alleviates Atherosclerosis through Inducing Immune Response and Regulating Lipid Metabolism in Apoe-/- Mice.

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe-/- mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe-/- mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.

Characteristics of anti-contactin1 antibody positive autoimmune nodopathies combined with membranous nephropathy.

BACKGROUND: Autoimmune nodopathy (AN) is a very rare new disease entity, especially when combined with membranous nephropathy (MN). METHODS: Antibodies against nodal-paranodal cell adhesion molecules in the serum were detected using cell-based assays. Antibody subtypes against contactin-1 (CNTN1) were confirmed. Cases of anti-CNTN1 antibody-positive AN with and without MN were retrieved through a literature search to compare clinical and electrophysiological characteristics. RESULTS: A 65-year-old male patient with MN developed limb numbness and weakness, along with walking instability. Serum CNTN1 antibodies were positive, primarily those of the IgG4 subtype. Electromyography showed prominent demyelination patterns in both the proximal and distal segments of the nerves compared to the middle nerve trunk. Magnetic resonance imaging revealed enlargement of the bilateral brachial and lumbosacral plexuses and local hyperintensity of the right C5-C6 nerve roots. Thirty-five cases with anti-CNTN1 antibody-positive AN with MN and 51 cases with anti-CNTN1 antibody-positive AN without MN were compared. Furthermore, the proportion of patients with MN combined with AN presenting with acute or subacute onset was higher than that observed in the MN without AN group. Nevertheless, no substantial differences were noted between the two groups concerning the clinical and electrophysiological characteristics, which were mainly elderly men, manifested as sensory ataxia, IgG4 antibody subtype, electrophysiological demyelination, and a certain effect on immunotherapy. CONCLUSION: In cases of electrophysiological manifestation of demyelinating peripheral neuropathy, especially in distal and poximal segments of nerves, AN should be considered, and further screening for renal function should be performed. Concomitant MN does not aggravate or alleviate peripheral nerve symptoms.

Aronia-derived anthocyanins and metabolites ameliorate TNFα-induced disruption of myogenic differentiation in satellite cells.

This study investigates the effects of Aronia berries, their primary anthocyanins and other second metabolites-mimicking dietary anthocyanin consumption-on enhancing muscular myogenesis under chronic inflammation. Murine muscle satellite cells (MuSCs) were cultured ex vivo, allowing for expansion and differentiation into myotubes. Myogenic differentiation was disrupted by TNFα at both early and terminal stages, with treatment using Aronia berries applied at physiologically relevant concentrations alongside TNFα. The results demonstrated that Aronia berries treatments, particularly phenolic metabolites, significantly stimulated the proliferative capacity of MuSCs. Furthermore, Aronia berries treatment enhanced early-stage myogenesis, marked by increased MymX and MyoG expression and nascent myotube formation, with metabolites showing the most pronounced effects. Aronia berry powder and individual anthocyanins exerted milder regulatory effects. Similar trends were observed during terminal differentiation, where Aronia berries treatment promoted myotube growth and inhibited TNFα-induced inflammatory atrophic ubiquitin-conjugating activity. Additionally, the secondary metabolites of Aronia berries significantly prevented muscle-specific ubiquitination in the dexamethasone-induced atrophy model. Overall, the treatment with Aronia berries enhanced myogenesis in a cellular model of chronic muscular inflammation, with Aronia-derived metabolites showing the strongest response, likely through TLR4/NF-κB modulation. In this case, enhanced regeneration capacity and anti-atrophy potential were associated with TLR4/NF-κB modulation.

Therapeutic targeting of GDF11 in muscle atrophy: Insights and strategies.

The exploration of novel therapeutic avenues for skeletal muscle atrophy is imperative due to its significant health impact. Recent studies have spotlighted growth differentiation factor 11 (GDF11), a TGFß superfamily member, for its rejuvenating role in reversing age-related tissue dysfunction. This review synthesizes current findings on GDF11, elucidating its distinct biological functions and the ongoing debates regarding its efficacy in muscle homeostasis. By addressing discrepancies in current research outcomes and its ambiguous role due to its homological identity to myostatin, a negative regulator of muscle mass, this review aims to clarify the role of GDF11 in muscle homeostasis and its potential as a therapeutic target for muscle atrophy. Through a thorough examination of GDF11's mechanisms and effects, this review provides insights that could pave the way for innovative treatments for muscle atrophy, emphasizing the need and strategies to boost endogenous GDF11 levels for therapeutic potential.

The role of estrogen in Alzheimer's disease pathogenesis and therapeutic potential in women.

Estrogens are pivotal regulators of brain function throughout the lifespan, exerting profound effects from early embryonic development to aging. Extensive experimental evidence underscores the multifaceted protective roles of estrogens on neurons and neurotransmitter systems, particularly in the context of Alzheimer's disease (AD) pathogenesis. Studies have consistently revealed a greater risk of AD development in women compared to men, with postmenopausal women exhibiting heightened susceptibility. This connection between sex factors and long-term estrogen deprivation highlights the significance of estrogen signaling in AD progression. Estrogen's influence extends to key processes implicated in AD, including amyloid precursor protein (APP) processing and neuronal health maintenance mediated by brain-derived neurotrophic factor (BDNF). Reduced BDNF expression, often observed in AD, underscores estrogen's role in preserving neuronal integrity. Notably, hormone replacement therapy (HRT) has emerged as a sex-specific and time-dependent strategy for primary cardiovascular disease (CVD) prevention, offering an excellent risk profile against aging-related disorders like AD. Evidence suggests that HRT may mitigate AD onset and progression in postmenopausal women, further emphasizing the importance of estrogen signaling in AD pathophysiology. This review comprehensively examines the physiological and pathological changes associated with estrogen in AD, elucidating the therapeutic potential of estrogen-based interventions such as HRT. By synthesizing current knowledge, it aims to provide insights into the intricate interplay between estrogen signaling and AD pathogenesis, thereby informing future research directions and therapeutic strategies for this debilitating neurodegenerative disorder.

Psychosocial Factors Linked to Uncontrolled Infection and Mortality among People Living with HIV Who Use Substances: A Latent Class Analysis.

To determine whether endorsement patterns of psychosocial symptoms revealed distinct subgroups, or latent classes, of people living with HIV who use substances (PLWH-SU), and to assess whether these classes demonstrated differential health outcomes over time. This study uses data from 801 PLWH-SU initially enrolled across 11 US hospitals during 2012-2014 and followed up in 2017. Latent class analysis included 28 psychosocial items. Regression analysis examined class membership as a predictor of viral suppression. Survival analysis examined class as a predictor of all-cause mortality. The selected model identified five unique classes. Individuals in classes characterized by more severe and more numerous psychosocial symptoms at baseline had lower likelihoods of viral suppression and survival. The study demonstrated the importance of considering patterns of overlapping psychosocial symptoms to identify subgroups of PLWH-SU and reveal their risks for adverse outcomes. Integration of primary, mental health, and substance use care is essential to address the needs of this population.

Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts.

Myocardial ischemia-reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia-reperfusion hearts. Myocardial ischemia-reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia-reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunohistochemistry and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia-reperfusion.

Genome-wide identification, characterization, and evolutionary analysis of the barley TALE gene family and its expression profiles in response to exogenous hormones.

Three-amino-loop-extension (TALE) family belongs to the homeobox gene superfamily and occurs widely in plants, playing a crucial role in regulating their growth and development. Currently, genome-wide analysis of the TALE family has been completed in many plants. However, the systematic identification and hormone response analysis of the TALE gene family in barley are still lacking. In this study, 21 TALE candidate genes were identified in barley, which can be divided into KNOX and BELL subfamilies. Barley TALE members in the same subfamily of the phylogenetic tree have analogically conserved motifs and gene structures, and segmental duplications are largely responsible for the expansion of the HvTALE family. Analysis of TALE orthologous and homologous gene pairs indicated that the HvTALE family has mainly undergone purifying selective pressure. Through spatial structure simulation, HvKNOX5-HvKNOX6 and HvKNOX5-HvBELL11 complexes are all formed through hydrogen bonding sites on both the KNOX2 and homeodomain (HD) domains of HvKNOX5, which may be essential for protein interactions among the HvTALE family members. Expression pattern analyses reveal the potential involvement of most HvTALE genes in responses to exogenous hormones. These results will lay the foundation for regulation and function analyses of the barley TALE gene family in plant growth and development by hormone regulation.

CT-based radiomics combined with clinical features for invasiveness prediction and pathological subtypes classification of subsolid pulmonary nodules.

Purpose: To construct optimal models for predicting the invasiveness and pathological subtypes of subsolid nodules (SSNs) based on CT radiomics and clinical features. Materials and Methods: This study was a retrospective study involving two centers. A total of 316 patients with 353 SSNs confirmed as atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) were included from January 2019 to February 2023. Models based on CT radiomics and clinical features were constructed for classification of AAH/AIS and MIA, MIA and IAC, as well as lepidic-predominant adenocarcinoma (LPA) and acinar-predominant adenocarcinoma (APA). Receiver operating characteristic (ROC) curve was used to evaluate the model performance. Finally, the nomograms based on the optimal models were established. Results: The nomogram based on the combined model (AAH/AIS versus MIA) consisting of lobulation, the GGN-vessel relationship, diameter, CT value, consolidation tumor ratio (CTR) and rad-score performed the best (AUC=0.841), while age, CT value, CTR and rad-score were the significant features for distinguishing MIA from IAC, the nomogram based on these features performed the best (AUC=0.878). There were no significant differences in clinical features between LPA and APA, while the radiomics model based on rad-score showed good performance for distinguishing LPA from APA (AUC=0.926). Conclusions: The nomograms based on radiomics and clinical features could predict the invasiveness of SSNs accurately. Moreover, radiomics models showed good performance in distinguishing LPA from APA.

Real-time dynamic polygenic prediction for streaming data.

Polygenic risk scores (PRSs) are promising tools for advancing precision medicine. However, existing PRS construction methods rely on static summary statistics derived from genome-wide association studies (GWASs), which are often updated at lengthy intervals. As genetic data and health outcomes are continuously being generated at an ever-increasing pace, the current PRS training and deployment paradigm is suboptimal in maximizing the prediction accuracy of PRSs for incoming patients in healthcare settings. Here, we introduce real-time PRS-CS (rtPRS-CS), which enables online, dynamic refinement and calibration of PRS as each new sample is collected, without the need to perform intermediate GWASs. Through extensive simulation studies, we evaluate the performance of rtPRS-CS across various genetic architectures and training sample sizes. Leveraging quantitative traits from the Mass General Brigham Biobank and UK Biobank, we show that rtPRS-CS can integrate massive streaming data to enhance PRS prediction over time. We further apply rtPRS-CS to 22 schizophrenia cohorts in 7 Asian regions, demonstrating the clinical utility of rtPRS-CS in dynamically predicting and stratifying disease risk across diverse genetic ancestries.