Effect of in-situ biochemical modification on the synthesis, structure, and function of xanthan gum based bacterial cellulose generated from Tieguanyin oolong tea residue hydrolysate.

The effect of in-situ biochemical modification on the synthesis, structure, and function of xanthan gum based bacterial cellulose generated from Tieguanyin oolong tea residue hydrolysate was evaluated for the first time. This modification could overcome the inhibitory effect of the hydrolysate and the bacterial cellulose yield with 0.6% xanthan gum addition increased by 260.8% compared with that without xanthan gum addition. Bacterial cellulose and xanthan gum were combined by the in-situ modification and the alteration of fermentation medium rheological properties by xanthan gum addition might be beneficial for their combination. The average diameter of the bacterial cellulose microfibrils was increased by the modification, and it had a great influence on the crystalline structure of the bacterial cellulose. Additionally, both the water absorption and texture properties of the bacterial cellulose was strengthened by the modification. Overall, this modification showed great potential for efficient and effective xanthan gum based bacterial cellulose production.

Effects of extracellular vesicle-derived noncoding RNAs on pre-metastatic niche and tumor progression.

A pre-metastatic niche (PMN) is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs. Extracellular vesicles (EVs) play a role in intercellular communication by delivering cargoes, such as noncoding RNAs (ncRNAs). The pivotal role of extracellular vesicle-derived noncoding RNAs (EV-ncRNAs) in the PMN has attracted increasing attention. In this review, we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression, vascular permeability and angiogenesis, inflammation, metabolic reprogramming, and fibroblast alterations. In particular, we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers. Finally, we discussed the promising clinical applications of EV-ncRNAs, including their potential as diagnostic and prognostic markers and therapeutic targets.

Protein-Ligand Blind Docking Using CB-Dock2.

Protein-ligand blind docking is a widely used method for studying the binding sites and poses of ligands and receptors in pharmaceutical and biological research. Recently, our new blind docking server named CB-Dock2 has been released and is currently being utilized by researchers worldwide. CB-Dock2 outperforms state-of-the-art methods due to its accuracy in binding site identification and binding pose prediction, which are enabled by its knowledge-based docking engine. This highly automated server offers interactive and intuitive input and output web interfaces, making it an efficient and user-friendly tool for the bioinformatics and cheminformatics communities. This chapter provides a brief overview of the methods, followed by a detailed guide on using the CB-Dock2 server. Additionally, we present a case study that evaluates the performance of protein-ligand blind docking using this tool.

Changes in flavor and biological activities of Lentinula edodes hydrolysates after Maillard reaction.

This study aimed to elucidate how the Maillard reaction (MR) affects the flavor and bioactivities of Lentinula edodes hydrolysates (LEHs). Changes in flavor were investigated using non-targeted metabolomics techniques (GC-MS and LC-MS/MS) and sensory evaluation. Simultaneously, UV absorption, fluorescence, and FT-IR spectra were used to characterize the process of MR. We also evaluated the effects of MR on the antioxidant activity, hypoglycemic activity and antimicrobial activity of LEHs in vitro. The results revealed that MR produced many volatile aldehydes and ketones and decreased the content of most amino acids, sugars and flavonoids in the LEHs while increasing the content of l-theanine and succinic acid. MRPs had a strong caramel and like-meat flavor and an obvious improvement in umami, taste continuity, and total acceptability. Furthermore, MR improved the antioxidant and antimicrobial properties of LEHs. This research establishes a theoretical foundation for MR in the deep processing of edible mushrooms.

Tuberostemonine may enhance the function of the SLC7A11/glutamate antiporter to restrain the ferroptosis to alleviate pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Stemona is a medicinal plant that has been used in China for thousands of years to treat respiratory diseases such as cough and tuberculosis. The tuberostemonine is the component of the Stemona tuberosa Lour., Stemona sessilifolia (Miq.) Miq. or Stemona japonica (Blume) Miq. (The plant name has been checked with http://www.theplantlist.org), of which multiple biological activities has been verified. However, whether it may alleviate pulmonary fibrosis via regulating ferroptosis mechanism has not been confirmed. AIM OF THE STUDY: The aim of this study is to observe whether tuberostemonine alleviates pulmonary fibrosis by enhancing the function of the SLC7A11/glutamate antiporter to restrain the ferroptosis. MATERIALS AND METHODS: We validated the effects of tuberostemonine and ferroptosis on TGF-ß1-induced proliferation of human lung fibroblast and bleomycin-induced pulmonary fibrosis in mice. In vitro, the ferroptosis effect of TGF-ß1 on human lung fibroblast were examined and the activity of ɑ-SMA, collagen, hydroxyproline and ferrous ions in cells were also examined. In vivo, ferroptosis impacts respiratory function. Inflammatory manifestations, hydroxyproline, collagen activity and ferrous ions in the lung or blood were subject to evaluation. RESULTS: Tuberostemonine significantly improved respiratory function in mice with bleomycin-induced pulmonary fibrosis, decreased cellular and lung hydroxyproline content, reduced inflammation and collagen deposition in cells and lung, and promoted an increase in the SLC7A11 and GPX4 proteins. Tuberostemonine inhibits the ferroptosis phenomenon, up-regulates SLC7A11, GPX4 and GSH, and down-regulates the accumulation of iron and ROS. CONCLUSIONS: Tuberostemonine significantly inhibited ferroptosis and improved pulmonary fibrosis both in vivo and vitro.

Interaction of Cerium Oxide Nanoparticles and Ionic Cerium with Duckweed (Lemna minor L.): Uptake, Distribution, and Phytotoxicity.

As one of the most widely used nanomaterials, CeO2 nanoparticles (NPs) might be released into the aquatic environment. In this paper, the interaction of CeO2 NPs and Ce3+ ions (0~10 mg/L) with duckweed (Lemna minor L.) was investigated. CeO2 NPs significantly inhibited the root elongation of duckweed at concentrations higher than 0.1 mg/L, while the inhibition threshold of Ce3+ ions was 0.02 mg/L. At high doses, both reduced photosynthetic pigment contents led to cell death and induced stomatal deformation, but the toxicity of Ce3+ ions was greater than that of CeO2 NPs at the same concentration. According to the in situ distribution of Ce in plant tissues by µ-XRF, the intensity of Ce signal was in the order of root > old frond > new frond, suggesting that roots play a major role in the uptake of Ce. The result of XANES showed that 27.6% of Ce(IV) was reduced to Ce(III) in duckweed treated with CeO2 NPs. We speculated that the toxicity of CeO2 NPs to duckweed was mainly due to its high sensitivity to the released Ce3+ ions. To our knowledge, this is the first study on the toxicity of CeO2 NPs to an aquatic higher plant.

Sex differences in mortality among children, adolescents, and young people aged 0-24 years: a systematic assessment of national, regional, and global trends from 1990 to 2021.

BACKGROUND: Differences in mortality exist between sexes because of biological, genetic, and social factors. Sex differentials are well documented in children younger than 5 years but have not been systematically examined for ages 5-24 years. We aimed to estimate the sex ratio of mortality from birth to age 24 years and reconstruct trends in sex-specific mortality between 1990 and 2021 for 200 countries, major regions, and the world. METHODS: We compiled comprehensive databases on the mortality sex ratio (ratio of male to female mortality rates) for individuals aged 0-4 years, 5-14 years, and 15-24 years. The databases contain mortality rates from death registration systems, full birth and sibling histories from surveys, and reports on household deaths in censuses. We modelled the sex ratio of age-specific mortality as a function of the mortality in both sexes using Bayesian hierarchical time-series models. We report the levels and trends of sex ratios and estimate the expected female mortality and excess female mortality rates (the difference between the estimated female mortality and the expected female mortality) to identify countries with outlying sex ratios. FINDINGS: Globally, the mortality sex ratio was 1·13 (ie, boys were more likely to die than girls of the same age) for ages 0-4 years (90% uncertainty interval 1·11 to 1·15) in 2021. This ratio increased with age to 1·16 (1·12 to 1·20) for 5-14 years, reaching 1·65 for 15-24 years (1·52 to 1·75). In all age groups, the global sex ratio of mortality increased between 1990 and 2021, driven by faster declines in female mortality. In 2021, the probability of a newborn male reaching age 25 years was 94·1% (93·7 to 94·4), compared with 95·1% for a newborn female (94·7 to 95·3). We found a disadvantage of females versus males (compared with countries with similar total mortality) in 2021 in five countries for ages 0-4 years (Algeria, Bangladesh, Egypt, India, and Iran), one country (Suriname) for ages 5-14 years, and 13 countries for ages 15-24 years (including Bangladesh and India). We found the reverse pattern (disadvantage of males vs females compared with countries of similar total mortality) in one country in ages 0-4 years (Vietnam) and eight countries in ages 15-24 years (including Brazil and Mexico). Globally, the number of excess female deaths from birth to age 24 years was 86 563 (-6059 to 164 000) in 2021, down from 544 636 (453 982 to 633 265) in 1990. INTERPRETATION: The global sex ratio of mortality for all age groups in the first 25 years of life increased between 1990 and 2021. Targeted interventions should focus on countries with outlying sex ratios of mortality to reduce disparities due to discrimination in health care, nutrition, and violence. FUNDING: The Bill & Melinda Gates Foundation, US Agency for International Development, and King Abdullah University of Science and Technology.

Confirmation of eosinophilic sialodochitis by terminal duct biopsy.

OBJECTIVE: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy. METHODS: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis. RESULTS: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis. CONCLUSION: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation.

Association of pulse pressure fluctuation during hospitalization with adverse outcomes within 3 months after ischemic stroke.

BACKGROUND: Pulse pressure (PP) depends on heart function and arterial wall elasticity, which is closely related to the incidence of ischemic stroke. However, the association of PP fluctuation during hospitalization with adverse outcomes after ischemic stroke remains unclear. METHODS: The present study included 3971 patients with ischemic stroke. The primary outcome was the composite outcome of death or vascular events within 3 months after ischemic stroke. PP fluctuation was reflected by successive variation of PP (PP-SV). RESULTS: The cumulative incidence rates of the primary outcome were the highest in the patients in the highest quartiles of PP-SV (P<0.05). The multivariable-adjusted HRs (95% CIs) of the primary outcome in the highest quartiles were 1.86 (1.03-3.38) for death or vascular events, and 2.15 (1.06-4.37) for vascular events (all Ptrend <0.05). Multivariable-adjusted restricted cubic spline analyses showed linear associations of PP-SV during hospitalization with the primary outcome (P for linearity < 0.05). CONCLUSIONS: Large PP fluctuation during hospitalization was associated with increased risks of adverse outcomes within 3 months after ischemic stroke, which provided valuable new insight for BP management in the acute phase of ischemic stroke. Controlling PP fluctuation may be contributing to improving prognosis after ischemic stroke.

Quantitative MRI Analysis of Brachial Plexus and Limb-Girdle Muscles in Upper Extremity Onset Amyotrophic Lateral Sclerosis.

BACKGROUND: Recent evidence highlights the potential of axonal degeneration as a biomarker for amyotrophic lateral sclerosis (ALS) detection. However, the diagnostic potential of peripheral nerve axon changes in ALS remains unclear. PURPOSE: To evaluate the diagnostic performance of quantitative MRI of the brachial plexus and limb-girdle muscles (LGMs) in patients with upper extremity onset of ALS. STUDY TYPE: Retrospective. POPULATION: 47 patients with upper extremity onset of ALS and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions with short-tau inversion recovery sequences, T2-weighted turbo spin-echo Dixon sequence. ASSESSMENT: The cross-sectional area (CSA) and nerve-muscle T2 signal intensity ratio (nT2) of the bilateral brachial plexus as well as the CSA and fat fraction (FF) of the bilateral LGMs were assessed by two radiologists. Disease severity and clinical stage of ALS patients were assessed by two neurologists. STATISTICAL TESTS: Student's t-test, Wilcoxon rank-sum test, binary logistic regression, interclass correlation coefficient, receiver operating characteristic analysis, and correlation analysis were performed for MRI quantitative metrics and clinical variables. Significance level: P < 0.05. RESULTS: In the affected limbs of patients with ALS, the CSA of the brachial plexus roots, trunks, and cords and the nT2 values of the brachial plexus trunks were significantly smaller than in the healthy controls. In the LGMs, the affected limbs of ALS showed significantly smaller CSA and higher FF than controls. The model containing parameters such as brachial plexus trunk CSA, subscapularis CSA, infraspinatus CSA, and subscapularis FF had excellent diagnostic efficacy for ALS. Additionally, increased subscapularis FF and supraspinatus FF were correlated with disease severity, and subscapularis CSA was negatively correlated with the clinical stage. DATA CONCLUSION: Brachial plexus thinning, LGM atrophy, and fatty infiltration might serve as MRI-derived biomarkers for ALS with upper extremity onset. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Drug in Therapeutic Polymer: Sinomenine-Loaded Oxidation-Responsive Polymeric Nanoparticles for Rheumatoid Arthritis Treatment.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that frequently involves cartilage damage and the destruction of the bone structure, ultimately resulting in disability and long-term pain. It is clear that overexpression of reactive oxygen species (ROS) and the complex inflammatory microenvironment are the main causes of RA pathogenesis; thereby, the efficacy of any single-drug treatment is limited. Herein, we formulated a therapeutic hyaluronic acid derivative (PAM-HA) with adsorption capacity to the subchondral bone, a long retention time within inflamed joints, and ROS-scavenging capacity, which was used as a drug carrier for realizing the controlled release of sinomenine (Sin) within arthritic joints. This "drug in therapeutic polymer" design strategy was aimed at realizing antioxidant and anti-inflammatory combination therapy for RA. In vivo experiments suggest that PAM-HA@Sin NPs can be retained in the inflamed joints of rats for a long time compared with commercially available free Sin injections. As expected, therapeutic PAM-HA polymeric carriers can increase joint lubrication and reduce oxidative stress, while the released Sin induces downregulation of proinflammatory factors (TNF-α and IL-1ß) and upregulation of anti-inflammatory factors (Arg-1 and IL-10) via the NF-κB pathway. In summary, a ROS-scavenging hyaluronic acid (HA) derivative was developed as the nanocarrier for Sin delivery to simultaneously remodel the oxidative/inflammatory microenvironment in RA, which opens up new horizons for the development of therapeutic polymers and the combined therapeutic strategies.

Description of Xanthocytophaga agilis sp. nov. and Xanthocytophaga flavus sp. nov. of the new genus Xanthocytophaga gen. nov and the proposal of Rhodocytophagaceae fam. nov. within the order Cytophagales.

Four Gram-staining-negative, aerobic, yellow-pigmented and rod-shaped bacteria, named strains BD1B2-1T, NT2B1T, YF14B1 and DM2B3-1, were isolated from four rhizosphere soil samples of banana in China. Comparison of the 16S rRNA gene sequences showed that all these strains were most closely related to an invalidly published species, 'Rhodocytophaga rosea' 172606-1, with similarities ranging from 87.7 to 88.0%. According to the phylogenomic analysis, the four strains were clustered in an independent lineage and closely related to the genus Rhodocytophaga. The genomic sizes of these strains were approximately 9.49-9.77 Mbp with the DNA G + C contents of 38.8-39.0 mol%. They all contained C16:1 ω5c, iso-C15:0 and iso-C17:0 3-OH as the major fatty acids and menaquinone 7 as the only respiratory quinone. They all had phosphatidylethanolamine as the major polar lipids. Based on phenotypic and phylogenomic characteristics, the four strains should represent two novel species within a novel genus, for which the names Xanthocytophaga agilis gen. nov., sp. nov. (BD1B2-1T = GDMCC 1.2890T = JCM 35374T) and Xanthocytophaga flavus sp. nov. (NT2B1T = GDMCC 1.2889T = JCM 35375T) are proposed; the former is assigned as the type species of the novel genus Xanthocytophaga gen. nov. In addition, based on the phenotypic and phylogenomic data, we proposed to reclassify the existing genus Rhodocytophaga in the family Cytophagaceae into a novel family Rhodocytophagaceae fam. nov. The novel family consists of the type genus Rhodocytophaga and the novel genus Xanthocytophaga.

IDegLira for type 2 diabetes: a systematic review and meta-analysis.

OBJECTIVES: IDegLira is a novel fixed-ratio soluble combination of insulin degludec and the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide approved for type 2 diabetes (T2D) patients. Individual trials have assessed the clinical profile of IDegLira vs different comparators. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of IDegLira for T2D. METHODS: PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched from inception to August 15, 2023. The primary outcomes included change from baseline in haemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS: This meta-analysis identified 1044 citations, and included 13 eligible trials, enroling 7773 patients. Compared with the control groups, IDegLira was optimal in change in HbA1c, percentage of patients achieving HbA1c < 7%, percentage of patients achieving HbA1c < 6.5%, HbA1c < 7.0% without weight gain and without severe or blood glucose (BG)-confirmed hypoglycaemia episodes, HbA1c < 6.5% without weight gain and without severe or BG-confirmed hypoglycaemia episodes, change in fasting plasma glucose, change in self-measured plasma glucose, change in systolic pressure, and total daily insulin dose. No difference was found between the IDegLira and control groups in terms of change in body weight, change in diastolic pressure, severe or BG-confirmed symptomatic hypoglycaemia, nocturnal severe or BG-confirmed symptomatic hypoglycaemia, adverse events or serious adverse events. CONCLUSIONS: In patients with T2D, IDegLira improved glycaemic control whilst balancing out risk for hypoglycaemia and gastrointestinal side effects.

Enhanced Electromechanical Performance in Lead-free (Na,K)NbO3-Based Piezoceramics via the Synergistic Design of Texture Engineering and Sm-Modification.

Next-generation electromechanical conversion devices have a significant demand for high-performance lead-free piezoelectric materials to meet environmentally friendly requirements. However, the low electromechanical properties of lead-free piezoceramics limit their application in high-end transducer applications. In this work, a 0.96K0.48Na0.52Nb0.96Sb0.04O3-0.04(Bi0.5-xSmx)Na0.5ZrO3 (abbreviated as T-NKN-xSm) ceramic was designed through phase regulation and texture engineering, which is expected to solve this difficulty. Through our research, we successfully demonstrated the enhanced electromechanical performance of lead-free textured ceramics with a highly oriented [001]c orientation. Notably, the T-NKN-xSm textured ceramics doped with 0.05 mol % Sm exhibited the optimal electromechanical performance: piezoelectric coefficient d33 ≈ 710 pC N-1, longitudinal electromechanical coupling k33 ≈ 0.88, planar electromechanical coupling kp ≈ 0.80, and Curie temperature Tc ≈ 244 °C. Finally, we conducted a detailed investigation into the phase and domain structures of the T-NKN-Sm ceramics, providing valuable insights for achieving high electromechanical properties in NKN-based ceramics. This research serves as a crucial reference for the development of advanced electromechanical devices by facilitating the utilization of lead-free piezoelectric materials with superior performance and environmental benefits.

Small extracellular vesicles from irradiated lung epithelial cells promote activation of fibroblasts in pulmonary fibrosis.

Background: Alveolar epithelial injury and dysfunction are the risk factors for radiation-induced pulmonary fibrosis (RIPF). However, it is not clear about the relationship between RIPF and the small extracellular vesicles (sEV) secreted by irradiated alveolar epithelial cells. Based on the activation of fibroblasts, this study explored the role of sEV derived from alveolar epithelial cells in RIPF and the potential mechanisms.Methods: Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were used to characterize sEV. Western blotting was used to detect fibrosis-associated proteins. Cell counts and transwell assays were used to evaluate the proliferation and migration ability of fibroblasts. RT-PCR was used to observe the extracellular matrix (ECM) synthesized by fibroblasts, miRNA changes in the sEV were determined by second-generation sequencing.Results: TEM, NTA and western blotting showed the extracellular vesicles with a double-layer membrane structure of approximately 100 nm in diameter. The sEV derived from irradiated A549, HBEC3-KT and MLE12 cells upregulated FN1 and alpha-SMA proteins expression in fibroblasts and drived the fibroblast to myofibroblast transition, and the sEV from irradiated mouse bronchoalveolar lavage fluid (BALF) affirmed the same results. In addition, the sEV derived from irradiated alveolar epithelial cells significantly increased the migration ability of fibroblasts and the expression of extracellular matrix proteins such as FN1. The results of miRNA sequencing of sEV in BALF of rats with RIPF showed that the metabolic pathway may be important for miRNA to regulate the activation of fibroblasts.Conclusion: The sEV derived from radiated pulmonary epithelial cells promote the activation, migration and extracellular matrix proteins expression of lung fibroblasts; miRNA in sEV may be an important molecular that affects the activation of lung fibroblasts.

Development and Validation of a Recurrence-Free Survival Prediction Model for Locally Advanced Esophageal Squamous Cell Carcinoma with Neoadjuvant Chemoradiotherapy.

BACKGROUND: A recurrence-free survival (RFS) prediction model was developed and validated for patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy (NCRT) in combination with surgery. PATIENTS AND METHODS: We included 282 patients with esophageal squamous cell carcinoma who received neoadjuvant chemoradiotherapy (NCRT) combined with surgery, constructed three models incorporating pathological factors, investigated the discrimination and calibration of each model, and compared the clinical utility of each model using the net reclassification index (NRI) and the integrated discrimination index (IDI). RESULTS: Multivariable analysis showed that pathologic complete response (pCR) and lymph node tumor regression grading (LN-TRG) (p < 0.05) were independent prognostic factors for RFS. LASSO regression screened six correlates of LN-TRG, vascular invasion, nerve invasion, degree of differentiation, platelet grade, and a total diameter of residual cancer in lymph nodes to build model three, which was consistent in terms of efficacy in the training set and validation set. Kaplan-Meier (K-M) curves showed that all three models were able to distinguish well between high- and low-risk groups (p < 0.01). The NRI and IDI showed that the clinical utility of model 2 was slightly better than that of model 1 (p > 0.05), and model 3 was significantly better than that of model 2 (p < 0.05). CONCLUSIONS: Clinical prediction models incorporating LN-TRG factors have high predictive efficacy, can help identify patients at high risk of recurrence after neoadjuvant therapy, and can be used as a supplement to the  AJCC/TNM staging system while offering a scientific rationale for early postoperative intervention.

Epithelial Yap/Taz are required for functional alveolar regeneration following acute lung injury.

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz are normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2 to AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to a LPS injury prevented AT1 cell regeneration, led to intra-alveolar collagen deposition, and resulted in persistent innate inflammation. Together these findings established that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

Cross-Domain Unpaired Learning for Low-Dose CT Imaging.

Supervised deep-learning techniques with paired training datasets have been widely studied for low-dose computed tomography (LDCT) imaging with excellent performance. However, the paired training datasets are usually difficult to obtain in clinical routine, which restricts the wide adoption of supervised deep-learning techniques in clinical practices. To address this issue, a general idea is to construct a pseudo paired training dataset based on the widely available unpaired data, after which, supervised deep-learning techniques can be adopted for improving the LDCT imaging performance by training on the pseudo paired training dataset. However, due to the complexity of noise properties in CT imaging, the LDCT data are difficult to generate in order to construct the pseudo paired training dataset. In this paper, we propose a simple yet effective cross-domain unpaired learning framework for pseudo LDCT data generation and LDCT image reconstruction, which is denoted as CrossDuL. Specifically, a dedicated pseudo LDCT sinogram generative module is constructed based on a data-dependent noise model in the sinogram domain, and then instead of in the sinogram domain, a pseudo paired dataset is constructed in the image domain to train an LDCT image restoration module. To validate the effectiveness of the proposed framework, clinical datasets are adopted. Experimental results demonstrate that the CrossDuL framework can obtain promising LDCT imaging performance in both quantitative and qualitative measurements.

Preparation of a Dual-Functional Sulfated Galactofucan Polysaccharide/Poly(vinyl alcohol) Hydrogel to Promote Macrophage Recruitment and Angiogenic Potential in Diabetic Wound Healing.

A diabetic foot ulcer is a common high-risk complication in diabetic patients, but there is still no universal dressing for clinical treatment. In this study, a novel dual-functional sulfated galactofucan polysaccharide/poly(vinyl alcohol) hydrogel (DPH20) is developed during freeze-thaw cycles. Experimental results indicated that DPH20 had a high specific surface area, a dense porous structure, and a good swelling property, which could effectively adsorb the exudates and keep the wound moist. Furthermore, DPH20 exhibited remarkably recruited macrophage capability and accelerated the inflammation stage by improving the expression of the mRNA of CCL2, CCR2, and CCL22 in macrophages. DPH20 could promote cell migration and growth factor release to accelerate tube formation under hyperglycemic conditions in cell models of L929s and HUEVCs, respectively. Significantly, DPH20 accelerates the reconstruction of the full-thickness skin wound by accelerating the recruitment of macrophages, promoting angiogenesis, and releasing the growth factor in the diabetic mouse model. Collectively, DPH20 is a promising multifunctional dressing to reshape the damaged tissue environment and accelerate wound healing. This study provides an efficient strategy to repair and regenerate diabetic skin ulcers.

A sight of self-assembly mechanism in fish oil oleogels: Phase transition, crystal structure and non-covalent interaction.

Fish oils contain ω-3 polyunsaturated fatty acids (PUFAs), but easily cause quality deterioration due to the oxidation. Beeswax-based oleogels could wrap fish oils by beeswax self-assembly. The phase transition, crystal structure and non-covalent interaction were investigated to reveal the self-assembly mechanism from the perspective of beeswax and oil phase characteristics. The results indicated that high unsaturation degree, PUFAs and beeswax additions promoted phase transition, SFC and stable crystal networks. The changes of crystal structures were ascribed to the polymorphism and polymorphic transition. ß-Polymorphs could form crystal networks, and ß'-polymorphs could influence the size of crystal chains or clusters as well as crystalline domains. Crystalline domain sizes affected crystal morphologies and network structures, including plate-like structures and multi-layer porous structures. UFAs could involve the beeswax self-assembly to change structure characteristics by van der Waals forces and π-π stacking. The OBC remained 100%, when beeswax additions reached more than 6%. Hence, beeswax additions, PUFA contents and unsaturation degree all influenced the self-assembly mechanism and adjusted the macroscopic properties of oleogels.