Ginsenoside Rh4 prevents endothelial dysfunction as a novel AMPK activator.

BACKGROUND AND PURPOSE: The AMP-activated protein kinase (AMPK) signalling pathway is a desirable target for various cardiovascular diseases (CVD), while the involvement of AMPK-mediated specific downstream pathways and effective interventions in hyperlipidaemia-induced endothelial dysfunction remain largely unknown. Herein, we aim to identify an effective AMPK activator and to explore its efficacy and mechanism against endothelial dysfunction. EXPERIMENTAL APPROACH: Molecular docking technique was adopted to screen for the potent AMPK activator among 11 most common rare ginsenosides. In vivo, poloxamer 407 (P407) was used to induce acute hyperlipidaemia in C57BL/6J mice. In vitro, palmitic acid (PA) was used to induce lipid toxicity in HAEC cells. KEY RESULTS: We discovered the strongest binding of ginsenoside Rh4 to AMPKα1 and confirmed the action of Rh4 on AMPK activation. Rh4 effectively attenuated hyperlipidaemia-related endothelial injury and oxidative stress both in vivo and in vitro and restored cell viability, mitochondrial membrane potential and mitochondrial oxygen consumption rate in HAEC cells. Mechanistically, Rh4 bound to AMPKα1 and simultaneously up-regulated AKT/eNOS-mediated NO release, promoted PGC-1α-mediated mitochondrial biogenesis and inhibited P38 MAPK/NFκB-mediated inflammatory responses in both P407-treated mice and PA-treated HAEC cells. The AMPK inhibitor Compound C treatment completely abrogated the regulation of Rh4 on the above pathways and weakened the lowering effect of Rh4 on endothelial impairment markers, suggesting that the beneficial effects of Rh4 are AMPK dependent. CONCLUSION AND IMPLICATIONS: Rh4 may serve as a novel AMPK activator to protect against hyperlipidaemia-induced endothelial dysfunction, providing new insights into the prevention and treatment of endothelial injury-associated CVD.

Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann's reversals.

BACKGROUND: Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann's reversal procedure in the prediction of short-term postoperative complications. METHODS: A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. RESULTS: Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. CONCLUSION: Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann's reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients.

Symplasmic and transmembrane zinc transport is modulated by cadmium in the Cd/Zn hyperaccumulator Sedum alfredii.

This study investigated the influence of Cd (25 µM) on Zn accumulation in a hyperaccumulating (HE) and a non-hyperaccumulating (NHE) ecotype of Sedum alfredii Hance at short-term supply of replete (Zn5, 5 µM) and excess (Zn400, 400 µM) Zn. Cd inhibited Zn accumulation in both ecotypes, especially under Zn400, in organs with active metal sequestration, i.e. roots of NHE and shoots of HE. Direct biochemical Cd/Zn competition at the metal-protein interaction and changes in transporter gene expression contributed to the observed accumulation patterns in the roots. Specifically, in HE, Cd stimulated SaZIP4 and SaPCR2 under Zn5, but downregulated SaIRT1 and SaZIP4 under Zn400. However, Cd downregulated related transporter genes, except for SaNRAMP1, in NHE, irrespective of Zn. Cadmium stimulated casparian strip (CSs) development in NHE, as part of the defense response, while it had a subtle effect on the (CS) in HE. Moreover, Cd delayed the initiation of the suberin lamellae (SL) in HE, but stimulated SL deposition in NHE under both Zn5 or Zn400. Changes in suberization were mainly ascribed to suberin-biosynthesis-related genes and hormonal signaling. Altogether, Cd regulated Zn accumulation mainly via symplasmic and transmembrane transport in HE, while Cd inhibited both symplasmic and apoplasmic Zn transport in NHE.

Artificial intelligence measured 3D body composition to predict pathological response in rectal cancer patients.

BACKGROUND: The treatment of locally advanced rectal cancer (LARC) is moving towards total neoadjuvant therapy and potential organ preservation. Of particular interest are predictors of pathological complete response (pCR) that can guide personalized treatment. There are currently no clinical biomarkers which can accurately predict neoadjuvant therapy (NAT) response but body composition (BC) measures present as an emerging contender. The primary aim of the study was to determine if artificial intelligence (AI) derived body composition variables can predict pCR in patients with LARC. METHODS: LARC patients who underwent NAT followed by surgery from 2012 to 2023 were identified from the Australian Comprehensive Cancer Outcomes and Research Database registry (ACCORD). A validated in-house pre-trained 3D AI model was used to measure body composition via computed tomography images of the entire Lumbar-3 vertebral level to produce a volumetric measurement of visceral fat (VF), subcutaneous fat (SCF) and skeletal muscle (SM). Multivariate analysis between patient body composition and histological outcomes was performed. RESULTS: Of 214 LARC patients treated with NAT, 22.4% of patients achieved pCR. SM volume (P = 0.015) and age (P = 0.03) were positively associated with pCR in both male and female patients. SCF volume was associated with decreased likelihood of pCR (P = 0.059). CONCLUSION: This is the first study in the literature utilizing AI-measured 3D Body composition in LARC patients to assess their impact on pathological response. SM volume and age were positive predictors of pCR disease in both male and female patients following NAT for LARC. Future studies investigating the impact of body composition on clinical outcomes and patients on other neoadjuvant regimens such as TNT are potential avenues for further research.

Correction: Liu et al. RANBP2 Activates O-GlcNAcylation through Inducing CEBPα-Dependent OGA Downregulation to Promote Hepatocellular Carcinoma Malignant Phenotypes. Cancers 2021, 13, 3475.

In the original publication [...].

Microbulbifer magnicolonia sp. nov., isolated from sediment of tidal flat located in Zhoushan, China.

A Gram-stain-negative, aerobic, motile with flagella and rod- or ovoid-shaped bacterium, designated GG15T, was isolated from tidal flat sediment sampled in Zhoushan, Zhejiang Province. Strain GG15T grew at 20-40 °C (optimum, 30 °C), at pH 5.5-9.5 (optimum, pH 7.0-8.0) and with 1.0-10.0 % (w/v) NaCl (optimum, 1.5 %). Colony diameters ranged from 1 to 3 mm within the first week, reaching a maximum of 6-7 mm after 15 days of cultivation. Strain GG15T exhibited highest 16S rRNA gene sequence similarity to Microbulbifer taiwanensis CCM 7856T (98.1 %), with similarity to other species within the genus Microbulbifer ranging from 97.8 to 93.8 %. Similarity values to other genera were below 93.8 %. Strain GG15T exhibited positive activity for ß-glucosidase, trypsin and chymotrypsin, whereas the reference strain showed negative activity. Chemotaxonomic analyses indicated that strain GG15T contained Q-8 as the sole respiratory quinone, C16 : 0 (9.1 %), iso-C15 : 0 (30.9 %) and iso-C11 : 0 3-OH (7.2 %) as the predominant fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids, four unidentified glycolipids, one unidentified phospholipid, two unidentified aminolipids and two unidentified aminophospholipids as the main polar lipids. The genome of strain GG15T was 4 307 641 bp long, comprising 3861 protein-coding genes. The G+C content of strain GG15T was 61.5 mol% based on its genomic sequence. Strain GG15T showed low digital DNA-DNA hybridization (<70 %) and average nucleotide identity values (<95 %) with other Microbulbifer species. As a result, a novel species within the genus Microbulbifer, named Microbulbifer magnicolonia sp. nov., is proposed. The type strain is GG15T (MCCC 1K08802T=KCTC 8210T).

A Potential Role of CD82/KAI1 during Uterine Decidualization in Mice.

The tumor metastasis suppressor gene CD82/KAI1 has been demonstrated to impact human trophoblast invasion and migration. Communication between trophoblasts and decidual stromal cells plays a crucial role in controlling the normal invasiveness of trophoblasts. However, whether CD82/KAI1 is involved in decidualization and what role it plays remain unclear. CD82/KAI1 demonstrates specific spatiotemporal expression patterns in stromal cells undergoing decidualization during pregnancy. This is observed in both naturally pregnant females post-implantation and pseudopregnant mice undergoing induced decidualization, as detected through in situ hybridization and immunofluorescence. CD82/KAI1 expression showed a significant time-dependent increase in cultured stromal cells after 24 and 48 h of progesterone (P4) and estrogen (E2) treatment. This was accompanied by a notable upregulation of decidualization markers, including cyclin D3 and PR. After transducing stromal cells with the adenovirus-overexpressing CD82/KAI1 for 48 h, the expression of cyclin D3 protein increased. Meanwhile, there was an attenuated expression of CD82/KAI1 due to an adenovirus siRNA knockdown, whereas cyclin D3 and PR expressions were not affected. Our findings suggest a potential role of CD82/KAI1 in regulating the process of decidualization, providing insights into stromal cell differentiation.

Investigation of clinical medicine undergraduates' recognition of narrative medicine.

BACKGROUND: Narrative Medicine (NM), a contemporary medical concept proposed in the 21st century, emphasizes the use of narrative as a literary form in medicine. This study aims to explore the understanding about NM and willingness to learn NM among medical students in our hospital. METHODS: A questionnaire survey was conducted among 130 students at Xiangya Medical College of Central South University. RESULTS: The findings revealed that a small percentage of students (3.1%) were familiar with narrative medicine and its training methods. Knowledge about the treatment skills (77.7%) and core content (55.4%) of narrative medicine was limited among the students. Despite this, a majority (63.1%) expressed a lack of interest in further understanding and learning about narrative medicine. Surprisingly, the survey indicated that students possessed a high level of narrative literacy, even without formal training in narrative medicine. Additionally, over half of the surveyed students (61.5%) believed that narrative medicine could benefit their clinical practice. CONCLUSIONS: This study serves as a preliminary basis for the future development of narrative medicine education in China. It highlights the need to prioritize medical humanities education and provide medical students with more opportunities to access information on narrative medicine. By doing so, we can strive to enhance the visibility and promote the integration of narrative medicine into medical humanities education in China.

Efficacy and safety of Yangxue Qingnao Granules in treatment of migraine: A systematic review and meta-analysis.

BACKGROUND: Yangxue Qingnao Granules (YXQN) is a Chinese patent medicine that has been commonly used in the clinical treatment of migraine. AIM: To assess the efficacy and safety of YXQN alone for the treatment of migraine. METHODS: We searched 10 databases to identify relevant randomized controlled trials (RCTs) published before September 2022. Two review authors independently searched and screened the literature, extracted the data, and assessed the methodological quality of the studies using criteria from ROB 2.0, and analyzed the data using Review Manager 5.4 software. RESULTS: A total of 12 RCTs including 767 participants with migraine met the selection criteria. We divided these studies into comparisons of YXQN with placebo, routine treatment drugs, and other Chinese patent medicines. The meta-analysis showed the following: (1) Efficacy: The YXQN group outperformed the placebo group [relative risk (RR) = 0.29, 95% confidence interval (95%CI): 0.15-0.43, P < 0.00001], routine treatment group (RR = 0.18, 95%CI: 0.09-0.27, P < 0.0001), and Chinese patent medicine group (RR = 0.27, 95%CI: 0.13-0.41, P < 0.001); (2) frequency of headache: There was a significant difference between YXQN vs placebo [mean difference (MD) = -1.25, 95%CI: -1.60 to -0.90, P < 0.00001], routine treatment drugs (MD = -0.85, 95%CI: -1.15 to -0.56, P < 0.00001), and Chinese patent medicine (MD = -0.91, 95%CI: -1.35 to -0.46, P < 0.0001); (3) headache duration: We found great heterogeneity between studies, with no differences between YXQN and placebo (MD = -0.61, 95%CI: -1.53 to -0.31, P = 0.19) and routine treatment drugs (MD = -0.22, 95%CI: -0.89 to 0.46, P < 0.53). YXQN was more effective than other Chinese patent medicines in reducing headache duration (MD = -1.24, 95%CI: -1.70 to -0.77, P < 0.00001); and (4) headache severity: There was no significant difference between YXQN vs placebo (MD = -1.67, 95%CI: -3.52 to 0.19, P = 0.08), routine treatment drugs (MD = -0.53, 95%CI: -2.02 to 0.96, P = 0.68), and other Chinese patent medicines (MD = -0.49, 95%CI: -2.83 to 1.85, P = 0.68). Mild gastrointestinal adverse reactions were reported in three cases. CONCLUSION: This study revealed that YXQN is effective and safe for treatment of migraine.

Genome variation and LTR-RT analyses of an ancient peach landrace reveal mechanism of blood-flesh fruit color formation and fruit maturity date advancement.

Peach (Prunus persica) landrace has typical regional characteristics, strong environmental adaptability, and contains many valuable genes that provide the foundation for breeding excellent varieties. Therefore, it is necessary to assemble the genomes of specific landraces to facilitate the localization and utilization of these genes. Here, we de novo assembled a high-quality genome from an ancient blood-fleshed Chinese landrace Tianjin ShuiMi (TJSM) that originated from the China North Plain. The assembled genome size was 243.5 Mb with a contig N50 of 23.7 Mb and a scaffold N50 of 28.6 Mb. Compared with the reported peach genomes, our assembled TJSM genome had the largest number of specific structural variants (SVs) and long terminal repeat-retrotransposons (LTR-RTs). Among the LTR-RTs with the potential to regulate their host genes, we identified a 6688 bp LTR-RT (named it blood TE) in the promoter of NAC transcription factor-encoding PpBL, a gene regulating peach blood-flesh formation. The blood TE was not only co-separated with the blood-flesh phenotype but also associated with fruit maturity date advancement and different intensities of blood-flesh color formation. Our findings provide new insights into the mechanism underlying the development of the blood-flesh color and determination of fruit maturity date and highlight the potential of the TJSM genome to mine more variations related to agronomic traits in peach fruit.

Advances of machine learning-assisted small extracellular vesicles detection strategy.

Detection of extracellular vesicles (EVs), particularly small EVs (sEVs), is of great significance in exploring their physiological characteristics and clinical applications. The heterogeneity of sEVs plays a crucial role in distinguishing different types of cells and diseases. Machine learning, with its exceptional data processing capabilities, offers a solution to overcome the limitations of conventional detection methods for accurately classifying sEV subtypes and sources. Principal component analysis, linear discriminant analysis, partial least squares discriminant analysis, XGBoost, support vector machine, k-nearest neighbor, and deep learning, along with some combined methods such as principal component-linear discriminant analysis, have been successfully applied in the detection and identification of sEVs. This review focuses on machine learning-assisted detection strategies for cell identification and disease prediction via sEVs, and summarizes the integration of these strategies with surface-enhanced Raman scattering, electrochemistry, inductively coupled plasma mass spectrometry and fluorescence. The performance of different machine learning-based detection strategies is compared, and the advantages and limitations of various machine learning models are also evaluated. Finally, we discuss the merits and limitations of the current approaches and briefly outline the perspective of potential research directions in the field of sEV analysis based on machine learning.

Iridium-catalyzed selective arylation of B(6)-H of 3-aryl-o-carboranes with arylboronic acid via direct B-H activation.

This work discloses an iridium-catalyzed selective arylation of B(6)-H of 3-Ar-o-carboranes with arylboronic acid via direct B-H activation for the first time. A series of unsymmetric and symmetric 3,6-diaryl-o-carboranes decorated with diverse active groups have been synthesized with moderate to excellent yields under mild conditions. This work offers an efficient approach for selective arylation of B(6)-H with arylboronic acid and has important value for selective functionalization of o-carboranes.

[Retracted] MicroRNA­138 suppresses proliferation, invasion and glycolysis in malignant melanoma cells by targeting HIF­1α.

[This retracts the article DOI: 10.3892/etm.2016.3220.].

Generative Large Language Models for Detection of Speech Recognition Errors in Radiology Reports.

This study evaluated the ability of generative large language models (LLMs) to detect speech recognition errors in radiology reports. A dataset of 3233 CT and MRI reports was assessed by radiologists for speech recognition errors. Errors were categorized as clinically significant or not clinically significant. Performances of five generative LLMs-GPT-3.5-turbo, GPT-4, text-davinci-003, Llama-v2-70B-chat, and Bard-were compared in detecting these errors, using manual error detection as the reference standard. Prompt engineering was used to optimize model performance. GPT-4 demonstrated high accuracy in detecting clinically significant errors (precision, 76.9%; recall, 100%; F1 score, 86.9%) and not clinically significant errors (precision, 93.9%; recall, 94.7%; F1 score, 94.3%). Text-davinci-003 achieved F1 scores of 72% and 46.6% for clinically significant and not clinically significant errors, respectively. GPT-3.5-turbo obtained 59.1% and 32.2% F1 scores, while Llama-v2-70B-chat scored 72.8% and 47.7%. Bard showed the lowest accuracy, with F1 scores of 47.5% and 20.9%. GPT-4 effectively identified challenging errors of nonsense phrases and internally inconsistent statements. Longer reports, resident dictation, and overnight shifts were associated with higher error rates. In conclusion, advanced generative LLMs show potential for automatic detection of speech recognition errors in radiology reports. Keywords: CT, Large Language Model, Machine Learning, MRI, Natural Language Processing, Radiology Reports, Speech, Unsupervised Learning Supplemental material is available for this article.

Nuclear Factor Erythroid 2 Related Factor 2 and Mitochondria Form a Mutually Regulating Circuit in the Prevention and Treatment of Metabolic Syndrome.

Significance: Metabolic syndrome (MetS) has become a major global public health problem and there is an urgent need to elucidate its pathogenesis and find more effective targets and modalities for intervention. Recent Advances: Oxidative stress and inflammation are two of the major causes of MetS-related symptoms such as insulin resistance and obesity. Nuclear factor erythroid 2 related factor 2 (Nrf2) is one of the important systems responding to oxidative stress and inflammation. As cells undergo stress, cysteines within Kelch-like ECH-associated protein 1 (Keap1) are oxidized or electrophilically modified, allowing Nrf2 to escape ubiquitination and be translocated from the cytoplasm to the nucleus, facilitating the initiation of the antioxidant transcriptional program. Meanwhile, a growing body of evidence points out a specific modulation of mitochondrial homeostasis by Nrf2. After nuclear translocation, Nrf2 activates downstream genes involved in various aspects of mitochondrial homeostasis, including mitochondrial biogenesis and dynamics, mitophagy, aerobic respiration, and energy metabolism. In turn, mitochondria reciprocally activate Nrf2 by releasing reactive oxygen species and regulating antioxidant enzymes. Critical Issues: In this review, we first summarize the interactions between Nrf2 and mitochondria in the modulation of oxidative stress and inflammation to ameliorate MetS, then propose that Nrf2 and mitochondria form a mutually regulating circuit critical to maintaining homeostasis during MetS. Future Directions: Targeting the Nrf2-mitochondrial circuit may be a promising strategy to ameliorate MetS, such as obesity, diabetes, and cardiovascular diseases.

Developments and current status of cell-free DNA in the early detection and management of hepatocellular carcinoma.

Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.

Effects of water quality on bacterial inactivation by ferrate(VI).

Ferrate (Fe(VI)) is an emerging green oxidant which has great potential and prospect in water disinfection. However, the effects of water quality on Fe(VI) disinfection remain unclear. This study systematically investigated the effects of pH, organic matters and inorganic ions on Fe(VI) inactivation of Escherichia coli (E. coli). Results showed that pH was the dominant influencing factor and the inactivation efficiency as well as inactivation rate constant was negatively correlated with pH (6.8-8.4). HFeO4- was found to be the critical Fe(VI) species contributing to the inactivation. As for organic matters (0-5 mg C/L), protein and humic acid significantly accelerated the decay of Fe(VI) and had negative effects on the inactivation efficiency, while polysaccharide slightly inhibited the inactivation due to the low reactivity with Fe(VI). As for inorganic ions, bicarbonate (0-2 mM) could stabilize Fe(VI) and decreased the inactivation rate constant, while ammonium (0-1 mM) had little effect on the inactivation of E. coli. In addition, the comprehensive effects of water quality on Fe(VI) disinfection in actual reclaimed water were also evaluated. The inactivation of E. coli in secondary effluent and denitrifying effluent was found to be inhibited compared to that in phosphate buffer. Overall, this study is believed to provide valuable information on Fe(VI) disinfection for water and wastewater treatment practices.

The association of body composition on chemotherapy toxicities in non-metastatic colorectal cancer patients: a systematic review.

BACKGROUND: In recent years, certain body composition measures, assessed by computed tomography (CT), have been found to be associated with chemotherapy toxicities. This review aims to explore available data on the relationship between skeletal muscle and adiposity, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular and intermuscular adipose tissue and their association with chemotherapy toxicity in non-metastatic colorectal cancer (CRC) patients. METHODS: A systematic literature search following PRISMA guidelines was conducted in Medline, Embase, Cochrane and Web of Science, for papers published between 2011 and 2023. The search strategy combined keywords and MESH terms relevant to 'body composition', 'chemotherapy toxicities', and 'non-metastatic colorectal cancer'. RESULTS: Out of 3868 studies identified, six retrospective studies fulfilled the inclusion criteria with 1024 eligible patients. Low skeletal muscle mass was strongly associated with increased incidence of both chemotherapy toxicities and dose-limiting toxicity (DLT). The association of VAT, intramuscular and intermuscular adiposity was heterogeneous and inconclusive. There was no association between SAT and chemotherapy intolerance. No universal definitions or cut-offs for sarcopenia and obesity were noted. All studies utilized 2-dimensional (2D) CT slices for CT body composition assessment with varied selection on the vertebral landmark and inconsistent reporting of tissue-defining Hounsfield unit (HU) measurements. CONCLUSION: Low skeletal muscle is associated with chemotherapy toxicities in non-metastatic CRC. However, quality evidence on the role of adiposity is limited and heterogeneous. More studies are needed to confirm these associations with an emphasis on a more coherent body composition definition and an approach to its assessment, especially regarding sarcopenia.

Defective mesenchymal Bmpr1a-mediated BMP signaling causes congenital pulmonary cysts.

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study, we dissected the roles of BMP receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Ductile adhesive elastomers with force-triggered ultra-high adhesion strength.

Elastomers play a vital role in many forthcoming advanced technologies in which their adhesive properties determine materials' interface performance. Despite great success in improving the adhesive properties of elastomers, permanent adhesives tend to stick to the surfaces prematurely or result in poor contact depending on the installation method. Thus, elastomers with on-demand adhesion that is not limited to being triggered by UV light or heat, which may not be practical for scenarios that do not allow an additional external source, provide a solution to various challenges in conventional adhesive elastomers. Herein, we report a novel, ready-to-use, ultra high-strength, ductile adhesive elastomer with an on-demand adhesion feature that can be easily triggered by a compression force. The precursor is mainly composed of a capsule-separated, two-component curing system. After a force-trigger and curing process, the ductile adhesive elastomer exhibits a peel strength and a lap shear strength of 1.2 × 104 N m-1 and 7.8 × 103 kPa, respectively, which exceed the reported values for advanced ductile adhesive elastomers. The ultra-high adhesion force is attributed to the excellent surface contact of the liquid-like precursor and to the high elastic modulus of the cured elastomer that is reinforced by a two-phase design. Incorporation of such on-demand adhesion into an elastomer enables a controlled delay between installation and curing so that these can take place under their individual ideal conditions, effectively reducing the energy cost, preventing failures, and improving installation processes.