Tracing the origin of alveolar stem cells in lung repair and regeneration.

Alveolar type 2 (AT2) cells are stem cells of the alveolar epithelia. Previous genetic lineage tracing studies reported multiple cellular origins for AT2 cells after injury. However, conventional lineage tracing based on Cre-loxP has the limitation of non-specific labeling. Here, we introduced a dual recombinase-mediated intersectional genetic lineage tracing approach, enabling precise investigation of AT2 cellular origins during lung homeostasis, injury, and repair. We found AT1 cells, being terminally differentiated, did not contribute to AT2 cells after lung injury and repair. Distinctive yet simultaneous labeling of club cells, bronchioalveolar stem cells (BASCs), and existing AT2 cells revealed the exact contribution of each to AT2 cells post-injury. Mechanistically, Notch signaling inhibition promotes BASCs but impairs club cells' ability to generate AT2 cells during lung repair. This intersectional genetic lineage tracing strategy with enhanced precision allowed us to elucidate the physiological role of various epithelial cell types in alveolar regeneration following injury.

Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

Continuous genetic monitoring of transient mesenchymal gene activities in distal tubule and collecting duct epithelial cells during renal fibrosis.

Epithelial cells (ECs) have been proposed to contribute to myofibroblasts or fibroblasts through epithelial-mesenchymal transition (EMT) during renal fibrosis. However, since EMT may occur dynamically, transiently, and reversibly during kidney fibrosis, conventional lineage tracing based on Cre-loxP recombination in renal ECs could hardly capture the transient EMT activity, yielding inconsistent results. Moreover, previous EMT research has primarily focused on renal proximal tubule ECs, with few reports of distal tubules and collecting ducts. Here, we generated dual recombinases-mediated genetic lineage tracing systems for continuous monitoring of transient mesenchymal gene expression in E-cadherin+ and EpCAM+ ECs of distal tubules and collecting ducts during renal fibrosis. Activation of key EMT-inducing transcription factor (EMT-TF) Zeb1 and mesenchymal markers αSMA, vimentin, and N-cadherin, were investigated following unilateral ureteral obstruction (UUO). Our data revealed that E-cadherin+ and EpCAM+ ECs did not transdifferentiate into myofibroblasts, nor transiently expressed these mesenchymal genes during renal fibrosis. In contrast, in vitro a large amount of cultured renal ECs upregulated mesenchymal genes in response to TGF-ß, a major inducer of EMT.

Flexible Bioinspired Healable Antibacterial Electronics for Intelligent Human-Machine Interaction Sensing.

Flexible electronic sensors are receiving numerous research interests for their potential in electronic skins (e-skins), wearable human-machine interfacing, and smart diagnostic healthcare sensing. However, the preparation of multifunctional flexible electronics with high sensitivity, broad sensing range, fast response, efficient healability, and reliable antibacterial capability is still a substantial challenge. Herein, bioinspired by the highly sensitive human skin microstructure (protective epidermis/spinous sensing structure/nerve conduction network), a skin bionic multifunctional electronics is prepared by face-to-face assembly of a newly prepared healable, recyclable, and antibacterial polyurethane elastomer matrix with conductive MXene nanosheets-coated microdome array after ingenious templating method as protective epidermis layer/sensing layer, and an interdigitated electrode as signal transmission layer. The polyurethane elastomer matrix functionalized with triple dynamic bonds (reversible hydrogen bonds, oxime carbamate bonds, and copper (II) ion coordination bonds) is newly prepared, demonstrating excellent healability with highly healing efficiency, robust recyclability, and reliable antibacterial capability, as well as good biocompatibility. Benefiting from the superior mechanical performance of the polyurethane elastomer matrix and the unique skin bionic microstructure of the sensor, the as-assembled flexible electronics exhibit admirable sensing performances featuring ultrahigh sensitivity (up to 1573.05 kPa-1 ), broad sensing range (up to 325 kPa), good reproducibility, the fast response time (≈4 ms), and low detection limit (≈0.98 Pa) in diagnostic human healthcare monitoring, excellent healability, and reliable antibacterial performance.

Impact of viral filters on accuracy of cardiopulmonary testing and spirometry.

The present study found that using viral filters at the proximal end of a spirometry and CPET test circuit did not significantly alter the test results, with the exception of a marginal decrease noted in peak work rate https://bit.ly/3Vkew95.

Highly flame retardancy, barrier, mechanical and persistent antibacterial polylactic acid film with high-parallel interconnected thousand layered cake architecture.

In this work, a bio-based material (CGP) is obtained by combing chitosan, gelatin and polyvinyl alcohol through a simple solution mixing to simultaneously address polylactic acid film (PLA)' flammability and poor barrier, toughness and antibacterial properties by soaking. The results of open fire testing show that modified PLA films can effectively prolong the combustion time, improve the thermal stability and reduce the release of heat in the cone calorimeter test. For the PLA sample after soaking for 5 times (PLA-5) in particular, it can reduce the peak heat release rate (pHRR) and total heat release (THR) values to 85.8 kW/m2 and 1.3 MJ/m2 from the values of 129.5 kW/m2 and 1.8 MJ/m2 for PLA, respectively. Structural analysis suggests that CGP primarily operates in the condensed phase by forming physical barriers. Meanwhile, the modified PLA films can exhibit superior barrier effects, which indicate the oxygen transmission rate value of PLA-5 decreases to 0.9 cm3/(m2·day) from the 392.5 cm3/(m2·day) of raw PLA film. Moreover, the PLA-5 also have excellent toughness (the value increased to 200.5 % from 31.0 %) and persistent antibacterial effects (it still has 100 % sterilization after 500 days).

Schiff base fluorescent sensor with aggregation induced emission characteristics for the sensitive and specific Fe3+ detection.

An aggregation induced emission based compound ((E)-4-((2-hydroxy-5-methoxybenzylidene)amino)benzoic acid) was synthesized through facile Schiff base condensation and characterized by various spectral techniques. The as-prepared compound represented a typical aggregation induced emission behavior in aqueous solution and exploited as a turn-off fluorescent sensor for Fe3+ detection in THF-H2O system (3:7, v/v) with high sensitivity and selectivity. The mechanism of the fluorescence quenching was intensively studied, which was attributed to both dynamic quenching and inner filter effect. The fluorescence probe displayed a highly broad dynamic response range (0.5-500 µM) for selective detection of Fe3+ with a limit of detection of 0.079 µM. The proposed method was successfully employed for detection and quantification of Fe3+ in human urine samples and proved to have potential for practical applications in biological field.

Evaluating Fluorinated-Aniline Units with Functionalized Spiro[Fluorene-9,9'-Xanthene] as Hole-Transporting Materials in Perovskite Solar Cells and Light-Emitting Diodes.

In the field of perovskite optoelectronics, developing hole-transporting materials (HTMs) on the spiro[fluorene-9,9'-xanthene] (SFX) platform is one of the current research focuses. The SFX inherits the merits of spirobifluorene in terms of the configuration and property, but it is more easily derivatized and regulated by virtue of its binary structure. In this work, we design and synthesize four isomeric SFX-based HTMs, namely m-SFX-mF, p-SFX-mF, m-SFX-oF, and p-SFX-oF, through varying the positions of fluorination on the peripheral aniline units and their substitutions on the SFX core, and the optoelectronic performance of the resulting HTMs is evaluated in both perovskite solar cells (PSCs) and light-emitting diodes (PeLEDs) by the vacuum thermal evaporating hole-transporting layers (HTLs). The HTM p-SFX-oF exhibits an improved power conversion efficiency of 15.21% in an inverted PSC using CH3NH3PbI3 as an absorber, benefiting from the deep HOMO level and good HTL/perovskite interface contact. Meanwhile, the HTM m-SFX-mF provides a maximum external quantum efficiency of 3.15% in CsPb(Br/Cl)3-based PeLEDs, which is attributed to its perched HOMO level and shrunken band-gap for facilitating charge carrier injection and then exciton combination. Through elucidating the synergistic position effect of fluorination on aniline units and their substitutions on the SFX core, this work lays the foundation for developing low-cost and efficient HTMs in the future.

Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells.

BACKGROUND/AIM: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells. MATERIALS AND METHODS: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells. RESULTS: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins. CONCLUSION: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.

A freely precessing magnetar following an X-ray outburst.

Magnetars-highly magnetized neutron stars-are thought to be the most likely progenitors for fast radio bursts (FRBs). Freely precessing magnetars are further invoked to explain the repeating FRBs. We report here on new high-cadence radio observations of the magnetar XTE J1810-197 recorded shortly after an X-ray outburst. We interpret the polarization variations of the magnetar radio emission as evidence for the magnetar undergoing free precession following the outburst while its magnetosphere slowly untwists. The observations of precession being damped on a timescale of months argue against the scenario of freely precessing magnetars as the origin of repeating FRBs. Using free-precession models based on relaxing ellipticity with a decay of the wobble angle, we find the magnetar ellipticity to be in good agreement with theoretical predictions from nuclear physics. Our precise measurement of the magnetar's geometry can also further help in refining the modelling of X-ray light curves and constrain the star's compactness.

Integrated analysis of the lncRNA-associated competing endogenous RNA network in salt sensitivity of blood pressure.

Accumulating evidence showed that competing endogenous RNA (ceRNA) mechanism plays a pivotal role in salt sensitivity of blood pressure (SSBP). We constructed a ceRNA network based on SSBP-related differently expressed lncRNAs (2), mRNAs (73) and miRNAs (18). Bioinformatic analyses were utilized to analyze network and found network genes participate in biological pathways related to SSBP pathogenesis such as regulation of nitric oxide biosynthetic process (GO:0045,428) and cellular response to cytokine stimulus (GO:0071,345). Fourteen candidate ceRNA pathways were selected from network to perform qRT-PCR validation and found nine RNAs (KCNQ1OT1, SLC8A1-AS1, IL1B, BCL2L11, KCNJ15, CX3CR1, KLF2, hsa-miR-362-5p and hsa-miR-423-5p) differently expressed between salt-sensitive (SS) and salt-resistant (SR) groups (P < 0.05). Four ceRNA pathways were further validated by luciferase reporter assay and found KCNQ1OT1→hsa-miR-362-5p/hsa-miR-423-5p→IL1B pathways may influence the pathogenic mechanism of SS. Our findings suggested the ceRNA pathway and network may affect SS occurrence mainly through endothelial dysfunction and inflammatory activation.