Bioinspired radiative cooling coating with high emittance and robust self-cleaning for sustainably efficient heat dissipation.

To overcome the overheating phenomena of electronic devices and energy components, developing advanced energy-free cooling coatings with promising radiative property seem an effective and energy-saving way. However, the further application of these coatings is greatly limited by their sustainability because of their fragile and easy contamination. Herein, it is reported that a bioinspired radiative cooling coating (BRCC) displayed sustainably efficient heat dissipation by the combination of high emittance and robust self-cleaning property. With the hierarchical porous structure constructed by multiwalled carbon nanotubes (MWCNTs), modified SiO2 and fluorosilicone (FSi) resin, the involvement of the BRCC improves the cooling performance by increasing ≈25% total heat transfer coefficient. During the abrasion and soiling tests, the BRCC-coated Al alloy heat sink always displays stable radiative cooling performance. Moreover, the simulation and experimental results both revealed that reducing surface coverage of BRCC (≈80.9%) can still keep highly cooling efficiency, leading to a cost-effective avenue. Therefore, this study may guide the design and fabrication of advanced radiative cooling coating.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.

Whole-heart coronary calcium Agatston score is a well-established predictor of major adverse cardiovascular events (MACE), but it does not account for individual calcification features related to the pathophysiology of the disease (e.g., multiple-vessel disease, spread of the disease along the vessel, stable calcifications, numbers of lesions, and density). We used novel, hand-crafted calcification features (calcium-omics); Cox time-to-event modeling; elastic net; and up and down synthetic sampling methods for imbalanced data, to assess MACE risk. We used 2457 CT calcium score (CTCS) images enriched for MACE events from our large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were especially important determinants of increased risk, with dense calcification (> 1000HU, stable calcifications) associated with reduced risk Our calcium-omics model with (training/testing, 80/20) gave C-index (80.5%/71.6%) and 2-year AUC (82.4%/74.8%). Although the C-index is notoriously impervious to model improvements, calcium-omics compared favorably to Agatston and gave a significant difference (P < 0.001). The calcium-omics model identified 73.5% of MACE cases in the high-risk group, a 13.2% improvement as compared to Agatston, suggesting that calcium-omics could be used to better identity candidates for intensive follow-up and therapies. The categorical net-reclassification index was NRI = 0.153. Our findings from this exploratory study suggest the utility of calcium-omics in improved risk prediction. These promising results will pave the way for more extensive, multi-institutional studies of calcium-omics.

AI prediction of cardiovascular events using opportunistic epicardial adipose tissue assessments from CT calcium score.

Background: Recent studies have used basic epicardial adipose tissue (EAT) assessments (e.g., volume and mean HU) to predict risk of atherosclerosis-related, major adverse cardiovascular events (MACE). Objectives: Create novel, hand-crafted EAT features, "fat-omics", to capture the pathophysiology of EAT and improve MACE prediction. Methods: We segmented EAT using a previously-validated deep learning method with optional manual correction. We extracted 148 radiomic features (morphological, spatial, and intensity) and used Cox elastic-net for feature reduction and prediction of MACE. Results: Traditional fat features gave marginal prediction (EAT-volume/EAT-mean-HU/BMI gave C-index 0.53/0.55/0.57, respectively). Significant improvement was obtained with 15 fat-omics features (C-index=0.69, test set). High-risk features included volume-of-voxels-having-elevated-HU-[-50, -30-HU] and HU-negative-skewness, both of which assess high HU, which as been implicated in fat inflammation. Other high-risk features include kurtosis-of-EAT-thickness, reflecting the heterogeneity of thicknesses, and EAT-volume-in-the-top-25%-of-the-heart, emphasizing adipose near the proximal coronary arteries. Kaplan-Meyer plots of Cox-identified, high- and low-risk patients were well separated with the median of the fat-omics risk, while high-risk group having HR 2.4 times that of the low-risk group (P<0.001). Conclusion: Preliminary findings indicate an opportunity to use more finely tuned, explainable assessments on EAT for improved cardiovascular risk prediction.

Self-Cleaning and Spectral Selective Membrane for Sustainable Radiative Cooling.

Radiative cooling materials have attracted great attention due to their superiority in energy-free cooling, especially for outdoor applications. However, outdoor cooling performance is threatened by surface pollution. Herein, we demonstrate a ternary compound system, including polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP), boron nitride nanosheets (BNNS), and hydrophobic silicon dioxide (SiO2), to synchronously achieve self-cooling and self-cleaning properties through biomimetically building a lotus-like papillomatous structure. The optimized membrane has a high infrared emissivity of 0.93, a sunlight reflectivity of 97.2%, and a water contact angle of 150.5°and not only efficiently cools the object to a suitable temperature but also protects the membrane from polluting and keeps cooling for a long time. The result shows that the membrane can cool a nonfebrile object by 30.5 and 1.7 °C for noon and night, respectively, and the noon and night-time temperature drops are 10.8 and 13.5 °C for the self-heating object, compared to the bare state. Meanwhile, the membrane always keeps self-cleaning if slurry is splashed onto its surface or it is exposed to slurry. Importantly, the integration of superhydrophobic and radiative cooling properties ensures that the membrane has permanent cooling performance by protecting it from being contaminated, which is significant for outdoor applications.

Enhancing cardiovascular risk prediction through AI-enabled calcium-omics.

Background: Coronary artery calcium (CAC) is a powerful predictor of major adverse cardiovascular events (MACE). Traditional Agatston score simply sums the calcium, albeit in a non-linear way, leaving room for improved calcification assessments that will more fully capture the extent of disease. Objective: To determine if AI methods using detailed calcification features (i.e., calcium-omics) can improve MACE prediction. Methods: We investigated additional features of calcification including assessment of mass, volume, density, spatial distribution, territory, etc. We used a Cox model with elastic-net regularization on 2457 CT calcium score (CTCS) enriched for MACE events obtained from a large no-cost CLARIFY program (ClinicalTrials.gov Identifier: NCT04075162). We employed sampling techniques to enhance model training. We also investigated Cox models with selected features to identify explainable high-risk characteristics. Results: Our proposed calcium-omics model with modified synthetic down sampling and up sampling gave C-index (80.5%/71.6%) and two-year AUC (82.4%/74.8%) for (80:20, training/testing), respectively (sampling was applied to the training set only). Results compared favorably to Agatston which gave C-index (71.3%/70.3%) and AUC (71.8%/68.8%), respectively. Among calcium-omics features, numbers of calcifications, LAD mass, and diffusivity (a measure of spatial distribution) were important determinants of increased risk, with dense calcification (>1000HU) associated with lower risk. The calcium-omics model reclassified 63% of MACE patients to the high risk group in a held-out test. The categorical net-reclassification index was NRI=0.153. Conclusions: AI analysis of coronary calcification can lead to improved results as compared to Agatston scoring. Our findings suggest the utility of calcium-omics in improved prediction of risk.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Stimuli-Actuated Turn-On Theranostic Nanoplatforms for Imaging-Guided Antibacterial Treatment.

Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.

Nanotherapeutics with immunoregulatory functions for the treatment of bacterial infection.

The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body's immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed.

Multifaceted Roles of Copper Ions in Anticancer Nanomedicine.

The significantly increased copper level in tumor tissues and serum indicates the close association of copper ions with tumor development, making copper ions attractive targets in the development of novel tumor treatment methods. The advanced nanotechnology developed in the past decades provides great potential for tumor therapy, among which Cu-based nanotherapeutic systems have received greater attention. Herein, the multifaceted roles of copper ions in cancer progression are summarized and the recent advances in the copper-based nanostructures or nanomedicines for different kinds of tumor therapies including copper depletion therapy, copper-based cytotoxins, copper-ion-based chemodynamic therapy and its combination with other treatments, and copper-ion-induced ferroptosis and cuproptosis activation are discussed. Furthermore, the perspectives for the further development of copper-ion-based nanomedicines for tumor therapy and clinic translation are presented by the authors.

Trajectories of lipids around the menopause transition in Chinese women: results of the Kailuan cohort study.

OBJECTIVE: To investigate changes in lipid parameters around the final menstrual period (FMP) in Chinese women. DESIGN: A prospective community-based cohort study. PATIENT(S): Three thousand seven hundred fifty six Chinese women from the Kailuan cohort study who participated in the first examination and reached their FMP by the end of the seventh examination. Health examinations were performed every 2 years. Multivariable piece-wise linear mixed-effect models were used for repeated measures of lipids as a function of time around FMP. INTERVENTION(S): Number of years before or after FMP at each examination. MAIN OUTCOME MEASURE(S): Lipids at each examination, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). RESULT(S): Total cholesterol, LDL-C, and TGs began to increase in early transition, regardless of baseline age. Moreover, TC and LDL-C had a maximum annual increase from 1 year before to 2 years after FMP; TGs had a maximum annual increase from early transition to the fourth-year after menopause. The trajectories in other postmenopause segments differed across subgroups of different baseline ages. Furthermore, HDL-C remained stable around FMP if baseline age was <45 years, whereas if baseline age was ≥45 years, HDL-C would first decline and then rise during postmenopause. Women with a higher body mass index (BMI) underwent less adverse changes in TC and TGs during postmenopause and had decline in HDL-C before menopause. A later FMP age was associated with less adverse changes in TC, LDL-C, and TGs and greater increase in HDL-C during postmenopause; it was associated with a greater increase in LDL-C during early transition. CONCLUSION(S): This repeated measurement cohort study of indigenous Chinese women demonstrated that, regardless of baseline age, the adverse effect of menopause on lipids was since early transition, and the most adverse change time was from 1 year before to 2 years after FMP; HDL-C decreased first and then increased during postmenopause in older women; BMI and FMP age affected lipid trajectory mainly during postmenopause. We highlighted positive lipid management during menopause to reduce the burden of postmenopausal dyslipidemia. For lipid stratification management in postmenopausal women, BMI and FMP age are important factors.

Improved bias and reproducibility of coronary artery calcification features using deconvolution.

Purpose: Our long-range goal is to improve whole-heart CT calcium scores by extracting quantitative features from individual calcifications. Here, we perform deconvolution to improve bias/reproducibility of small calcification assessments, which can be degraded at the normal CT calcium score image resolution. Approach: We analyzed features of individual calcifications on repeated standard (2.5 mm) and thin (1.25 mm) slice scans from QRM-Cardio phantom, cadaver hearts, and CARDIA study participants. Preprocessing to improve the resolution involved of Lucy-Richardson deconvolution with a measured point spread function (PSF) or three-dimensional blind deconvolution in which the PSF was iteratively optimized on high detail structures such as calcifications in images. Results: Using QRM with inserts having known mg-calcium, we determined that both blind and conventional deconvolution improved mass measurements nearly equally well on standard images. Further, deconvolved thin images gave an excellent recovery of actual mass scores, suggesting that such processing could be our gold standard. For CARDIA images, blind deconvolution greatly improved results on standard slices. Bias across 33 calcifications (without, with deconvolution) was (23%, 9%), (18%, 1%), and ( - 19 % , - 1 % ) for Agatston, volume, and mass scores, respectively. Reproducibility was (0.13, 0.10), (0.12, 0.08), and (0.11, 0.06), respectively. Mass scores were more reproducible than Agatston scores or volume scores. For many other calcification features, blind deconvolution improved reproducibility in 21 out of 24 features. Cadaver images showed similar improvements in bias/reproducibility and slightly better results with a measured PSF. Conclusions: Deconvolution improves bias and reproducibility of multiple features extracted from individual calcifications in CT calcium score exams. Blind deconvolution is useful for improving feature assessments of coronary calcification in archived datasets.

Random forest classifier improving phenylketonuria screening performance in two Chinese populations.

Phenylketonuria (PKU) is a genetic disorder with amino acid metabolic defect, which does great harms to the development of newborns and children. Early diagnosis and treatment can effectively prevent the disease progression. Here we developed a PKU screening model using random forest classifier (RFC) to improve PKU screening performance with excellent sensitivity, false positive rate (FPR) and positive predictive value (PPV) in all the validation dataset and two testing Chinese populations. RFC represented outstanding advantages comparing several different classification models based on machine learning and the traditional logistic regression model. RFC is promising to be applied to neonatal PKU screening.

Stimuli-responsive therapeutic systems for the treatment of diabetic infected wounds.

Diabetic wound infection is a common disease that has significantly reduced people's quality of life. Although tremendous achievements have been made in clinical treatment, the crucial challenge in diabetic infected wound management stems from the detrimental diabetic wound environment and the emergence of bacterial resistance after long-term medication, which result in a reduced efficacy, an increased dosage of medication, and severe side effects. To tackle these issues, it is of great significance to develop an innovative treatment strategy for diabetic wound infection therapy. Currently, the exploitation of nanobiomaterial-based therapeutic systems for diabetic infected wounds is booming, and therapeutic systems with a stimuli-responsive performance have received extensive attention. These therapeutic systems are able to accelerate diabetic infected wound healing due to the on-demand release of therapeutic agents in diabetic infected wounds in response to stimulating factors. Based on the characteristics of diabetic infected wounds, many endogenous stimuli-responsive (e.g., glucose, enzyme, hypoxia, and acidity) therapeutic systems have been employed for the targeted treatment of infected wounds in diabetic patients. Additionally, exogenous stimulants, including light, magnetism, and temperature, are also capable of achieving on-demand drug release and activation. In this review, the characteristics of diabetic infected wounds are presented, and then exogenous/endogenous stimuli therapeutic systems for the treatment of diabetic infected wounds are summarized. Finally, the current challenges and future outlook of stimuli-responsive therapeutic systems are also discussed.

Effects of different dosages esketamine on cardiac conduction and heterogeneity of Cx43: the epicardial mapping in guinea pigs.

Background: Esketamine is favored in clinical settings. Relative to other anesthetics it preserves protective airway reflexes, maintains spontaneous respiration, stabilizes hemodynamics, and alleviates neuropathic pain. This study sought to evaluate the cardiac safety of esketamine at 3 sub-anesthetic gradient concentrations. Methods: We examined the cardiac electrophysiological effects of esketamine with infusion rates of 0.125, 0.25, and 0.5 mg·kg-1·h-1. Short-term studies were performed in ventricular myocytes using patch-clamp techniques and optically mapped Langendorff-perfused guinea-pig hearts. Long-term studies were performed using Langendorff-perfused guinea-pig hearts and electrically mapping the receipt of the infusion for 3 hours. Results: Esketamine changed the action potential (AP) morphology of cardiomyocytes. Notably, it increased the resting membrane potential (RMP), attenuated the amplitude of action potential (APA), reduced the maximum upstroke velocity (Vmax), and shortened the action potential duration (APD) at 30% to 70%, which led to relatively prolonged monophasic action potentials (MAP) triangulation in G0.25 and G0.5. All the effects were partially eluted. Optical mapping demonstrated almost equal and heterogeneous conduction. G0.125 resulted in an increased heart rate (HR) accompanied by a shortened APD. No detectable arrhythmia was observed at the cycle lengths (CLs) used. Long-term electrical mapping demonstrated the dose-dependent deceleration of the Vmax and APA, but only prolonged the AP parameters in G0.5. Left-ventricular isochronal conduction maps revealed the conduction heterogeneities at G0.5, and conduction velocity (CV) was increased in G0.125 and G0.25. None of these effects were reversed on drug washout. Electrocardiogram (ECG) traces revealed an accelerated HR with the associated curtailment of QT intervals in G0.125; HRs were decreased in G0.25 and G0.5; the PR intervals and QRS duration differed between G0.125 and G0.25, G0.5, which elicited electrical alternans. Connexin43 (Cx43) expression were significantly decreased in G0.125, G0.25 and G0.5. Conclusions: These data provide a basic electrophysiology for esketamine. Specifically, we found that (I) various methods of esketamine infusion had different effects on cardiac conduction at different dosages; (II) the heterogeneous expression of Cx43 is associated with spatially dispersed conduction; and (III) potential cardiac risks should be considered for high-risk patients receiving continuous esketamine infusions of high dosages.

Bioinformatics prediction of potential mechanisms and biomarkers underlying dilated cardiomyopathy.

BACKGROUND: Heart failure is a health burden responsible for high morbidity and mortality worldwide, and dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. DCM is a disease of the heart muscle and is characterized by enlargement and dilation of at least one ventricle alongside impaired contractility with left ventricular ejection fraction < 40%. It is also associated with abnormalities in cytoskeletal proteins, mitochondrial ATP transporter, microvasculature, and fibrosis. However, the pathogenesis and potential biomarkers of DCM remain to be investigated. AIM: To investigate the candidate genes and pathways involved in DCM patients. METHODS: Two expression datasets (GSE3585 and GSE5406) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between the DCM patients and healthy individuals were identified using the R package "linear models for microarray data." The pathways with common DEGs were analyzed via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analyses. Moreover, a protein-protein interaction network (PPI) was constructed to identify the hub genes and modules. The MicroRNA Database was applied to predict the microRNAs (miRNAs) targeting the hub genes. Additionally, immune cell infiltration in DCM was analyzed using CIBERSORT. RESULTS: In total, 97 DEGs (47 upregulated and 50 downregulated) were identified. GO analysis showed that the DEGs were mainly enriched in "response to growth factor," "extracellular matrix," and "extracellular matrix structural constituent." KEGG pathway analysis indicated that the DEGs were mainly enriched in "protein digestion and absorption" and "interleukin 17 (IL-17) signaling pathway." The PPI network suggested that collagen type III alpha 1 chain (COL3A1) and COL1A2 contribute to the pathogenesis of DCM. Additionally, visualization of the interactions between miRNAs and the hub genes revealed that hsa-miR-5682 and hsa-miR-4500 interacted with both COL3A1 and COL1A2, and thus these miRNAs might play roles in DCM. Immune cell infiltration analysis revealed that DCM patients had more infiltrated plasma cells and fewer infiltrated B memory cells, T follicular helper cells, and resting dendritic cells. CONCLUSION: COL1A2 and COL3A1 and their targeting miRNAs, hsa-miR-5682 and hsa-miR-4500, may play critical roles in the pathogenesis of DCM, which are closely related to the IL-17 signaling pathway and acute inflammatory response. These results may provide useful clues for the diagnosis and treatment of DCM.

BMP4/ALK3 deficiency leads to Meckel's cartilage truncation mimicking the mandible Tessier 30 cleft.

OBJECTIVE: In chondrogenesis, BMP signaling was inferred to exhibit regional specificity during Meckel's cartilage morphogenesis. This study aimed to explore the differences in BMP signaling activity between different parts of Meckel's cartilage and the impacts of BMP4 or ALK3 deficiency on the development of Meckel's cartilage during embryogenesis. MATERIALS AND METHODS: The BRE-gal reporter mouse line was utilized to gain an overall picture of canonical BMP signaling activity, as assessed by X-gal staining. Mouse models lacking either Bmp4 or Alk3 in neural crest cells (Wnt1-Cre;Bmp4fl/fl and Wnt1-Cre;Alk3fl/fl ) were generated to explore the morphogenesis of Meckel's cartilage and the mandibular symphysis, as assessed by skeletal staining, histology, and immunostaining. RESULTS: Different parts of Meckel's cartilage exhibited activation of different combinations of BMP signaling pathways. In Wnt1-Cre;Bmp4fl/fl mutants, Sox9+ condensation of the chondrogenic rostral process failed to form, and the V-shaped Runx2+ tissue was split in the median mandibular symphysis. The Wnt1-Cre;Bmp4fl/fl and Wnt1-Cre;Alk3fl/fl mouse models both exhibited truncated Meckel's cartilage, aberrant mandibular intramembranous bone, and tongue muscle abnormalities. CONCLUSIONS: The central hard-tissue loss of both mutant mouse models led to a mandibular symphysis cleft, mimicking the typical sign of the median mandible Tessier 30 cleft in humans.

Augmented BMP4 signal impairs tongue myogenesis.

Tongue muscles are derived from mesodermal cells, while signals driven by cranial neural crest cells (CNCCs) regulate tongue myogenesis via tissue-tissue interaction. Based on such mechanisms of interaction, congenital tongue defects occur in CNC-related syndromes in humans. This study utilized a pathologic model for the syndrome of congenital bony syngnathia, Wnt1-Cre;pMes-Bmp4 mouse line, to explore impacts of enhanced CNCCs-originated BMP4 signal on tongue myogenesis via tissue-tissue interaction. Our results revealed that microglossia, a clinical phenotype of congenital bony syngnathia in humans exhibited in Wnt1-Cre;pMes-Bmp4 mice due to impaired myogenesis. The augmented BMP4 signal affected the distal distribution, proliferation, and differentiation of myogenic cells as well as tendon patterning, resulting in disarrangement and atrophy of tongue muscles and the loss of the anterior digastric muscle. This study demonstrated how a CNCCs-originated ligand impaired tongue myogenesis via a non-autonomous way, which provided potential formation mechanisms for understanding tongue abnormalities in CNC-related syndromes.

Multifunctional Membrane for Thermal Management Applications.

Space cooling and heating consume a large proportion of global energy, so passive thermal management materials (i.e., without energy input), especially dual-mode materials including cooling and heating bifunctions, are becoming more and more attractive in many areas. Herein, a function-switchable Janus membrane between cooling and heating consisting of a multilayer structure of polyvinylidene fluoride nanofiber/zinc oxide nanosheet/carbon nanotube/Ag nanowire/polydimethylsiloxane was fabricated for comprehensive thermal management applications. In the cooling mode, the high thermal radiation emissivity (89.2%) and sunlight reflectivity (90.6%) of the Janus membrane resulted in huge temperature drops of 8.2-12.6, 9.0-14.0, and 10.9 °C for a substrate, a closed space, and a semiclosed space, respectively. When switching to the heating mode, temperature rises of 3.8-4.6, 4.0-4.8, and 12.5 °C for the substrate, closed space, and semiclosed space, respectively, were achieved owing to the high thermal radiation reflectivity (89.5%) and sunlight absorptivity (74.1%) of the membrane. Besides, the Janus membrane has outstanding comprehensive properties of the membrane, including infrared camouflaging/disguising, electromagnetic shielding (53.1 dB), solvent tolerance, waterproof properties, and high flexibility, which endow the membrane with promising application prospects.

Increased detection of circulating tumor DNA by short fragment enrichment.

BACKGROUND: Circulating cell-free DNA (cfDNA) detection for non-invasive diagnosis requires higher sensitivity and accuracy due to the low circulating tumor DNA (ctDNA) content. Many methods have been developed to improve detection of ctDNA, including ultra-deep sequencing or enrichment of shorter cfDNA fragments, such as those in the range of 90-150 bp. METHODS: Here, we developed a method for single-stranded DNA (ssDNA) library preparation with a large proportion of magnetic beads to enrich the shorter cfDNA fragments. We aimed to determine if this could increase the ctDNA content and thus improve the sensitivity of ctDNA detection by testing the method in blood samples from patients with advanced cancers (non-small cell lung cancers, esophageal squamous cell carcinoma, cholangiocarcinoma, colorectal cancer and liver cancer). RESULTS: This method was able to obtain shorter cfDNA both in commercial cfDNA references and real world clinical cfDNA samples. Plasmid simulation experiments showed that using a large proportion of magnetic beads to construct the library could obtain more ctDNA derived from shorter-fragment plasmids, which could significantly improve the detection of ctDNA especially in the low-variant allele frequency sample. In real-world clinical samples, this method may be able to increase the opportunity to obtain alteration reads from short fragments, which was important to low frequency detection. CONCLUSIONS: The ssDNA library preparation with large proportion of magnetic beads could increase the opportunity to obtain alteration reads from short fragments, which is crucial for low variant allele frequency detection.

The Transcription Factor Shox2 Shapes Neuron Firing Properties and Suppresses Seizures by Regulation of Key Ion Channels in Thalamocortical Neurons.

Thalamocortical neurons (TCNs) play a critical role in the maintenance of thalamocortical oscillations, dysregulation of which can result in certain types of seizures. Precise control over firing rates of TCNs is foundational to these oscillations, yet the transcriptional mechanisms that constrain these firing rates remain elusive. We hypothesized that Shox2 is a transcriptional regulator of ion channels important for TCN function and that loss of Shox2 alters firing frequency and activity, ultimately perturbing thalamocortical oscillations into an epilepsy-prone state. In this study, we used RNA sequencing and quantitative PCR of control and Shox2 knockout mice to determine Shox2-affected genes and revealed a network of ion channel genes important for neuronal firing properties. Protein regulation was confirmed by Western blotting, and electrophysiological recordings showed that Shox2 KO impacted the firing properties of a subpopulation of TCNs. Computational modeling showed that disruption of these conductances in a manner similar to Shox2's effects modulated frequency of oscillations and could convert sleep spindles to near spike and wave activity, which are a hallmark for absence epilepsy. Finally, Shox2 KO mice were more susceptible to pilocarpine-induced seizures. Overall, these results reveal Shox2 as a transcription factor important for TCN function in adult mouse thalamus.