Mesenchymal Stem Cells-Derived Exosomes Alleviate Acute Lung Injury by Inhibiting Alveolar Macrophage Pyroptosis.

Acute lung injury (ALI) is an important pathological process of acute respiratory distress syndrome, yet there are limited therapies for its treatment. Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been shown to be effective in suppressing inflammation. However, the effects of MSCs-Exo on ALI and the underlying mechanisms have not been well elucidated. Our data showed that MSCs-Exo, but not exosomes derived from MRC-5 cells (MRC-5-Exo), which are human fetal lung fibroblast cells, significantly improved chest imaging, histological observations, alveolocapillary membrane permeability, and reduced inflammatory response in ALI mice model. According to miRNA sequencing and proteomic analysis of MSCs-Exo and MRC-5-Exo, MSCs-Exo may inhibit pyroptosis by miRNAs targeting caspase-1-mediated pathway, and by proteins with immunoregulation functions. Taken together, our study demonstrated that MSCs-Exo were effective in treating ALI by inhibiting the pyroptosis of alveolar macrophages and reducing inflammation response. Its mechanism may be through pyroptosis-targeting miRNAs and immunoregulating proteins delivered by MSCs-Exo. Therefore, MSCs-Exo may be a new treatment option in the early stage of ALI.

Impact of chronic obstructive pulmonary disease on the efficacy and safety of neoadjuvant immune checkpoint inhibitors combined with chemotherapy for resectable non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy. METHODS: A retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023. RESULTS: A total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042-8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1-21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox's regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111-0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively. CONCLUSIONS: The present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

Trophic niche and adaptation in highland lizards: sex has greater influences than species matching.

The plateau environments are typically arid, cool, and high altitude, posing formidable challenges to wildlife survival due to resource scarcity and harsh conditions. Unraveling ecological adaptability in severe conditions requires a deeper understanding of the niche characteristics of plateau species. Trophic niche, which is a comprehensive indicator describing the energy acquisition strategy of animals, remains relatively understudied in plateau species. Here, by combining stable isotopes and morphological data, we quantified the trophic niches of two allopatric lizard species (Phrynocephalus vlangalii and P. erythrurus) that live in the hinterland of the Qinghai-Tibetan Plateau, and explored how their trophic niches correlate with morphological and environmental factors. While both trophic niche and morphological traits were similar between species, noteworthy distinctions were observed between male and female Phrynocephalus lizards. The morphological traits associated with predation (i.e. limb length and head size) and reproduction (i.e. abdomen length), annual mean temperature, and sex played influential roles in shifting trophic niches. These results imply that sexual dimorphism may facilitate inter-sex divergence in resource utilization, leading to trophic niche variations in the highland lizards. Furthermore, extreme environmental stress can constrain interspecific divergence in morphological and trophic traits. Our findings illustrate the dynamic variations of trophic niches in highland lizards, contributing to a more comprehensive understanding of the adaptation strategies employed by lizard species in plateau environments.

Quality evaluation of the literature on clinical randomized controlled trials of traditional Chinese medicine for treatment of gastric precancerous lesions in the past 20 years. / ä¸­åŒ»è¯æ²»ç–—èƒƒç™Œå‰ç— å˜ä¸´åºŠéšæœºå¯¹ç §è¯•éªŒäºŒåå¹´æ–‡çŒ®è´¨é‡è¯„ä»·.

OBJECTIVES: To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years. METHODS: The RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the CNKI, Wanfang database, VIP, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional evaluation indicators. RESULTS: A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the risk of uncertainty for the allocation scheme concealment was 98.93%; the risk of uncertainty for blinding of patients or testers was 98.69%; the risk of uncertainty for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.45%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature mentioned who implemented the randomized program, 1.07% of the literature hid the randomized program and 1.31% of the studies were blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods. Additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation. CONCLUSIONS: The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence for clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.

Discovery of unique CYP716C oxidase involved in pentacyclic triterpene biosynthesis from Camptotheca acuminata.

Dozens of triterpenes have been isolated from Camptotheca acuminata, however, triterpene metabolism in this plant remains poorly understood. The common C28 carboxy located in the oleanane-type and ursane-type triterpenes indicates the existence of a functionally active triterpene, C28 oxidase, in this plant. Thorough mining and screening of the CYP716 genes were initiated using the multi-omics database for C. acuminata. Two CYP716A (CYP716A394 and CYP716A395) and three CYP716C (CYP716C80-CYP716C82) were identified based on conserved domain analyses and hierarchical cluster analyses. CYP716 microsomal proteins were prepared and their enzymatic activities were evaluated in vitro. The CYP716 classified into the CYP716C subfamily displays ß-amyrin oxidation activity, and CYP716A displays α-amyrin and lupeol oxidation activity, based on gas chromatography-mass spectrometry analyses. The oxidation products were determined based on their mass and nuclear magnetic resonance spectrums. The optimum reaction conditions and kinetic parameters for CYP716C were determined, and functions were verified in Nicotiana benthaminana. Relative quantitative analyses revealed that these CYP716C genes were enriched in the leaves of C. acuminata plantlets after 60 d. These results indicate that CYP716C plays a dominant role in oleanane-type triterpene metabolism in the leaves of C. acuminata via a substrate-specific manner, and CYP716A is responsible for ursane- and lupane-type triterpene metabolism in fruit. This study provides valuable insights into the unique CYP716C-mediated oxidation step of pentacyclic triterpene biosynthesis in C. acuminata.

Evaluation of the Clinical Value of KL-6 and Tumor Markers in Primary Sjögren's Syndrome Complicated with Interstitial Lung Disease.

OBJECTIVE: primary Sjögren's syndrome (pSS) is an autoimmune disease, of which the most common complication is interstitial lung disease (ILD). This study aimed to analyze the clinical value of Krebs von den Lungen-6 (KL-6), carcinoembryonic antigen (CEA), and carbohydrate antigen 153(CA153) in patients with pSS complicated with ILD (pSS-ILD), given that only few studies have evaluated this. METHODS: This is a cross-sectional study. Serum KL-6 levels (U/mL) were measured using chemiluminescence immunoassay, and concentrations of serum tumor markers were determined using the immunofluorescence method in 64 cases of pSS-ILD (pSS-ILD group), 23 cases without ILD (non-ILD group), and 45 healthy controls. The correlation between KL-6 and tumor markers as well as lung function was analyzed, and the factors that were associated with pSS-ILD were screened. RESULTS: The serum KL-6 was more abnormally increased in patients with pSS-ILD, and the serum KL-6, CEA, carbohydrate antigen 125 (CA125), and CA153 levels were significantly higher in the pSS-ILD group than in the non-ILD and healthy control groups (p < 0.05). KL-6, CEA, and CA153 were negatively correlated with forced vital capacity (FVC%), forced expiratory volume in 1 s (FEV1%), total lung capacity (TLC%), and diffusing capacity for carbon monoxide (DLCO%) (all p < 0.05). Multivariate logistic analysis showed that KL-6 was an independent factor associated with pSS-ILD. CONCLUSIONS: In conclusion, we evaluated the association between clinical values of KL-6, tumor markers, and pSS-ILD, and found that KL-6 and tumor markers such as CEA, CA153, and CA125 in patients with pSS-ILD were higher than in patients with non-ILD, and KL-6 was more abnormally increased and significantly associated with ILD development in patients with pSS.

Proteomics-Guided Mining and Characterization of Epoxidase Involved in Camptothecin Biosynthesis from Camptotheca acuminata.

The detailed metabolic map for camptothecin (CPT) biosynthesis in Camptotheca acuminata has been proposed according to our combined omics results. However, the CYP450-mediated epoxidation step in CPT biosynthesis remains unexplored. A proteomics-guided approach was used to identify and annotate the proteins enriched during the vigorous CPT metabolism period in mature C. acuminata and seedlings. Comparative analyses revealed that the CPT and flavonoid biosyntheses were vigorous in stems and all of the samples except the leaves, respectively. The CYP71BE genes were screened based on their enrichment patterns at the transcriptomic-proteomic level and biochemically characterized in Saccharomyces cerevisiae WAT11. Four CYP71BE proteins exhibited in vitro isoliquiritigenin epoxidase activity. Additionally, CYP71BE206 showed epoxidase activity toward strictosamide, the critical precursor for CPT biosynthesis, both in vitro and in Nicotiana benthamiana. In planta functional verification suggested that CYP71BE206 is involved in CPT biosynthesis. Their catalytic conditions were optimized, and the enzymatic parameters were determined. This study provides valuable insight into the CYP71BE-mediated epoxidation step for CPT biosynthesis and offers evidence to verify that the newly characterized epoxidase (CYP71BE206) is simultaneously responsible for the biosynthesis of CPT and the flavonoid in this plant. An evolution event probably happened on ancestral CYP71BE, resulting in the neofunctionalization of CYP71BE206.

Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies.

Meteorin-like, also known as Metrnl, Meteorin-ß, Subfatin, and Cometin, is a novel secreted protein exerting pleiotropic effects on inflammation, immunology, and metabolism. Earlier research on this hormone focused on regulating energy expenditure and glucose homeostasis. Consequently, several studies attempted to characterize the molecule mechanism of Metrnl in glucose metabolism and obesity-related disorders but reported contradictory clinical results. Recent studies gradually noticed its multiple protective functions in inflammatory immune regulations and cardiometabolic diseases, such as inducing macrophage activation, angiogenesis, tissue remodeling, bone formation, and preventing dyslipidemias. A comprehensive understanding of this novel protein is essential to identify its significance as a potential therapeutic drug or a biomarker of certain diseases. In this review, we present the current knowledge on the physiology of Metrnl and its roles in inflammation, immunology, and metabolism, including animal/cell interventional preclinical studies and human clinical studies. We also describe controversies regarding the data of circulation Metrnl in different disease states to determine its clinical application better.

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization.

Pulmonary fibrosis is characteristic of several human lung diseases that arise from various causes. Given that treatment options are fairly limited, mouse models continue to be an important tool for developing new anti-fibrotic strategies. In this study, intrapulmonary administration of bleomycin (BLM) is carried out by nasal nebulization to create a mouse model of pulmonary fibrosis that closely mimics clinical disease characteristics. C57BL/6 mice received BLM (7 U/mL, 30 min/day) by nasal nebulization for 3 consecutive days and were sacrificed on day 9, 16, or 23 to observe inflammatory and fibrotic changes in lung tissue. Nasal aerosolized BLM directly targeted the lungs, resulting in widespread and uniform lung inflammation and fibrosis. Thus, we successfully generated an experimental mouse model of typical human pulmonary fibrosis. This method could easily be used to study the effects of the administration of various nasal aerosols on lung pathophysiology and validate new anti-inflammatory and anti-fibrotic treatments.

MiR-3646 accelerates inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis in hypertension model.

BACKGROUND: Inflammatory response of human vascular smooth muscle cells (hVSMCs) is a driving factor in hypertension progression. It has been reported that miR-3646 was significantly up-regulated in serum samples from patients with coronary artery disease and acute myocardial infarction mice. However, its role and underlying molecular mechanism related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs remain unclear. OBJECTIVE: We aimed to explore the potential molecular mechanisms related to inflammatory response of angiotensin II (Ang II)-induced hVSMCs. METHODS: Ang II-induced hypertension model was established after hVSMCs treated with 1 µM Ang II at 24 h. The interaction between microRNA 3646 (miR-3646) and cytochrome P450 2J2 (CYP2J2) was assessed by dual-luciferase reporter gene assay. MTS assay, Lipid Peroxidation MDA Assay Kit, ELISA, Western blot, and qRT-PCR were performed to examine viability, malondialdehyde (MDA) level, inflammatory cytokine levels, and the level of genes and proteins. RESULTS: Our findings illustrated that miR-3646 was up-regulated but CYP2J2 was down-regulated in Ang II-induced hVSMCs. Mechanically, miR-3646 negatively targeted to CYP2J2 in Ang II-induced hVSMCs. These findings indicated that miR-3646 regulated inflammatory response of Ang II-induced hVSMCs via targeting CYP2J2. Moreover, functional researches showed that CYP2J2 overexpression alleviated inflammatory response of Ang II-induced hVSMCs via epoxyeicosatrienoic acids/peroxisome proliferator-activated receptor-γ (EETs/PPARγ) axis, and miR-3646 aggravated inflammatory response of Ang II-induced hVSMCs via mediating CYP2J2/EETs axis. CONCLUSION: MiR-3646 accelerated inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis. Our findings illustrated the specific molecular mechanism of miR-3646 regulating hypertension.

Correlation Between Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms and Renal Function in Elderly Men Aged 80 Years and Older.

Purpose: To investigate the relationship between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and renal function in elderly men aged 80 years and older. Patients and Methods: We selected 389 elderly men aged 80-97 years with BPH/LUTS hospitalized at The Second Division of General Geriatrics, The First Affiliated Hospital of Zhengzhou University, between July 2018 and July 2020. In the cross-sectional study, patients were divided into the treatment (233 patients) and non-treatment (156 patients) groups based on whether they received treatment for BPH/LUTS. In the prospective self-case-control study, we included 129 of the non-treatment group patients who received oral BPH/LUTS medication and completed the 6-month outpatient follow-up. We compared prostate indicators and renal function in the cross-sectional study and baseline and after-treatment data in the prospective self-case-control study. Multiple linear regression analysis was performed for risk factors affecting renal function before and after BPH/LUTS treatment. Results: In the cross-sectional study, renal function was significantly better in the treatment group than in the non-treatment group. In the subgroup analysis of the prospective self-case-control study, renal function significantly improved after treatment among patients with hypertension and those with chronic kidney disease (CKD) 3a, but not in the entire cohort. Multivariable linear regression analysis showed that hypertension (ß=2.06, 95% CI 0.40 to 3.71) and CKD 3a (ß=17.16, 95% CI 15.53 to 18.79) were independent risk factors for creatinine differences before and after treatment, whereas hypertension (ß=-2.27, 95% CI -3.65 to -0.89), CKD 3a (ß=-11.93, 95% CI -13.29 to -10.58), and baseline prostate volume (ß=-0.11, 95% CI -0.20 to -0.02) were independent risk factors for estimated glomerular filtration rate differences before and after treatment. Conclusion: Treatment for moderate and severe BPH/LUTS can improve renal function in elderly patients with hypertension or CKD 3a.

Molecular mechanism of XB130 adaptor protein mediates trastuzumab resistance in gastric cancer.

BACKGROUND: Recent studies have shown that the activation of PI3K/AKT signaling pathway is an essential molecular mechanism participating in trastuzumab resistance in HER2 + GC (gastric cancer). However, how can we effectively inhibit AKT activity associated with drug resistance during trastuzumab treatment? Screening inhibitors against the upstream receptors of PI3K/AKT signaling pathway or interacting proteins of members has become an important way. METHODS: In this study, western blot, qRT-PCR, CCK8, Co-IP and other techniques were used to explore possible mechanisms participating in trastuzumab resistance in vitro. Besides, the xenograft mouse model and GC tissue samples from patients were used to further validate the in-vitro results. RESULTS: The expression of XB130 adaptor protein was remarkably increased in GC cell lines resistant to trastuzumab, and knockdown of XB130 could reverse the resistance via downregulating p-AKT. In addition, p-SRC (Tyr416) was increased in resistant cells, which could facilitate the binding of XB130 to PI3K p85α. It was also discovered that XB130 could negatively regulate PTEN gene transcription, and thus a positive feedback loop was formed between SRC-XB130-PTEN. CONCLUSIONS: In HER2 + GC, XB130 contributes to trastuzumab resistance by stimulating the PI3K/AKT signaling pathway through binding to PI3K p85α under the mediation of SRC kinase and regulating PTEN gene transcription, and in turn forming a positive feedback loop between SRC-XB130-PTEN.

Identification and Characterization of Jasmonic Acid Methyltransferase Involved in the Formation of Floral Methyl Jasmonate in Hedychium coronarium.

Hedychium coronarium is a popular ornamental flower in tropical and subtropical areas due to its elegant appearance and inviting fragrance. Methyl jasmonate (MeJA) is one of the volatile compounds in the blooming flowers of H. coronarium. However, the molecular mechanism underlying floral MeJA formation is still unclear in H. coronarium. In this study, a total of 12 SABATH family genes were identified in the genome of H. coronarium, and their encoded proteins range from 366 to 387 amino acids. Phylogenetic analysis revealed seven clades in the SABATH family and a JMT ortholog clade, including two HcSABATH members. Combined with expression profiling of HcSABATH members, HcJMT1 was identified as the top candidate gene for floral MeJA biosynthesis. In vitro enzyme assays showed that HcJMT1 can catalyze the production of MeJA from jasmonic acid. Gene expression analysis indicated that HcJMT1 exhibited the highest expression in the labella and lateral petals, the major sites of MeJA emission. During flower development, the two MeJA isomers, major isomers in the products of the HcJMT1 protein, were released after anthesis, in which stage HcJMT1 displayed high expression. Our results indicated that HcJMT1 is involved in the formation of floral MeJA in H. coronarium.

Changes in Gelation Properties of Silver Carp Myosin Treated by Combination of High Intensity Ultrasound and NaCl.

The molecular behavior of myosin in a low-salt environment limited the production of surimi-based products. This study aimed to investigate the effect of the combination of high intensity ultrasound (HIU) and NaCl (0.1, 0.3, 0.5 mol/L) on the physicochemical indexes of myosin. The changes were evaluated by solubility, ultraviolet (UV) spectroscopy, dynamic rheological properties, water holding capacity (WHC), microstructures, etc. For control samples, the gelation properties of myosin strengthened upon NaCl increasing. Combination of HIU and NaCl significantly improved the solubility of myosin, which was due to the conformational changes and the exposure of reactive groups. Meanwhile, the particle size of myosin obviously decreased when observed by atomic force microscope, which in turn promoted the stability of myosin. Furthermore, the improvement in solution behaviors of myosin treated by combination of HIU and NaCl contributed to the gelation properties as well as the formation of compact microstructures, which obtained high WHC and low cooking loss of myosin gels. In conclusion, combination of HIU and NaCl induced the unfolding of myosin with the exposure of reactive groups, consequently facilitating the formation of denser microstructures. Moreover, the biggest degree of improvement in gelation properties was observed at 0.1 mol/L NaCl combined with HIU.

All-in-one calcium nanoflowers for dual outputs biosensor: A simultaneous strategy for depression drug evaluation and non-invasive stress assessment.

Although enzyme-based signal amplification has been well developed for biosensors, their application in low-abundance biomarker under complicated conditions detection remains challenge. Cortisol is a steroid hormone and a quantitative evaluation of cortisol can objectively assess stress and depression. However, various factors can induce slight cortisol changes in body fluids, and this in turn sets a strict requirement for bedside testing of cortisol for evaluation of stress. Herein, all-in-one calcium nanoflowers (CaHPO4-AM-HRP-SA NFs) integrated with horseradish peroxidase (HRP), α-amylase (α-AM), and streptavidin (SA) have been synthesized to develop a simple but powerful biosensor for cortisol detection. High specific surface area and allosteric modulator provided by the hybrid nanoflowers as inherent advantages significantly boosted the catalytical ability and stability compared with the free enzymes. CaHPO4-AM-HRP-SA NFs also endowed the sensor with two output signals of one sample, leading the as-prepared sensor to realize self-calibration detection. Aside from using a traditional microplate reader to measure the signal, it could also be read out by a handheld blood glucose meter and a mobile phone. The sensor exhibited attractive simplicity and sensitivity with a low LOD of 98.5 pg mL-1. It accomplished the sensitive evaluation of cortisol in rat serum and assessed the antidepressant effects of different medications. The non-invasive and reliable cortisol detection is also achieved in human urine and saliva samples. Overall, we have demonstrated that the sensor can be deployed as a promising platform to evaluate drug efficiency and monitor stress in a simple and non-invasive manner.

Morphological Variation and Its Environmental Correlates in the Taihangshan Swelled-Vented Frog across the Qinling Mountains.

The Taihangshan swelled-vented frog (Feirana taihangnica), an endemic species to the Qinling Mountains, central China, has experienced a dramatic population decline over the last few decades. The aim of this work was to quantify morphological variation in F. taihangnica across the Qinling Mountains and examine environmental correlates of this variation of morphological traits. We implemented a hierarchical partitioning to estimate the independent contribution of each environmental variable on morphological variations. Temperature seasonality was the greatest contributor in variations of snout-vent length (SVL) and head width, and ultraviolet-B (UV-B) radiation of the lowest month was the most influential on both thigh length and tibia width. Then, we used generalized additive models to analyze the relationship between each environmental factor and morphological trait variations. Along the increasing of annual mean temperature, SVL decreased firstly and then increased, indicating no support for Bergmann's rule. Furthermore, SVL was negatively correlated with annual precipitation, while positively with temperature seasonality. The mean UV-B of the highest and lowest months was positively and negatively correlated with head width, thigh length and tibia width, respectively. The results of this study help us to understand adaptive potential of this mountain frog species via morphological variations in the light of environmental changes.

Structure-based identification and pathway elucidation of flavonoids in Camptotheca acuminate.

Flavonoid metabolism in Camptotheca acuminate remained an untapped area for years. A tandem MS approach was used and focused on the mining and characterizing of flavonoids in mature C. acuminate. Fifteen new flavonoids and forty-three known flavonoids, including fifteen flavone analogs, sixteen flavonol analogs, seven flavanone analogs, six chalcone analogs, four xanthone analogs, ten flavane analogs were mined and identified based on their MS/MS fragments. Fifty-three of them were firstly characterized in C. acuminate. Eight biosynthetic precursors for these flavonoids were also identified. We constructed a specific metabolic map for flavonoids according to their relative contents in the flowers, fruits, stems, and leaves of C. acuminate. Furthermore, the most probable genes involved in chalcone biosynthesis, flavonoid hydroxylation, methylation, and glycosylation were further mined and fished in the gene reservoir of C. acuminate according to their conserved domains and co-expression analysis. These findings enable us to acquire a better understanding of versatile flavonoid metabolism in C. acuminate.

Every road leads to Rome: therapeutic effect and mechanism of the extracellular vesicles of human embryonic stem cell-derived immune and matrix regulatory cells administered to mouse models of pulmonary fibrosis through different routes.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. Whether extracellular vesicles are effective in treating IPF and what is the optimal administrative route is not clear. Our previous studies have shown that immunity and matrix regulatory cells (IMRCs) derived from human embryonic stem cells can safely treat lung injury and fibrosis in mouse models, and its mechanism of action is related to the paracrine effect. In this study, we investigated the therapeutic effects of IMRC-derived extracellular vesicles (IMRC-EVs) on a bleomycin-induced pulmonary fibrosis mouse model and explored the optimal route of administration. METHODS: To study the biodistribution of IMRC-EVs after administration via different routes, NIR labeled-IMRC-EVs were delivered by intratracheal (IT) or intravenous (IV) route, and in vivo imaging was acquired at different time points. The therapeutic effects of IMRC-EVs delivered by different routes were analyzed by assessing histology, lung function, cytokines levels, and transcriptome profiling. RNA-seq of lung tissues was performed to investigate the mechanisms of EV treatment through IT or IV administrations. RESULTS: IMRC-EVs mainly reserved in the liver and spleen when administrated via IV route; and mainly retained in the lungs via the IT route. IMRC-EVs administrated via both routes demonstrated a therapeutic effect as attenuated pulmonary fibrosis, improved lung function, and histological parameters. Based on our RNA-seq results, different pathways may be affected by IMRC-EVs administrated via IT or IV routes. In addition, in vitro experiments showed that IMRC-EVs inhibited epithelial-to-mesenchymal transition induced by TGF-ß. CONCLUSION: IMRC-EVs administrated via IT or IV routes generate different biodistributions, but are both effective for the treatment of bleomycin-induced pulmonary fibrosis. The therapeutic mechanisms of IMRC-EVs administrated via different routes may be different.

The Incidence and Characteristics of Perinatal Stroke in Beijing: A Multicenter Study.

Objective: To assess the incidence, risk factors, and clinical characteristics of perinatal stroke in Beijing. Methods: This multicenter prospective study included all the live births from 17 representative maternal delivery hospitals in Beijing from March 1, 2019 to February 29, 2020. Neonates with a stroke were assigned to the study group. Clinical data, including general information, clinical manifestations, and risk factors, were collected. Up until 18 months after birth, neonates were routinely assessed according to the Ages and Stages Questionnaire (ASQ) and/or the Bayley scale. Statistical analysis was done using the chi-squared, t-tests, and logistic regression analysis using SPSS version 26.0. Outcomes: In total, 27 cases were identified and the incidence of perinatal stroke in Beijing was 1/2,660 live births, including 1/5,985 for ischemic stroke and 1/4,788 for hemorrhagic stroke. Seventeen cases (62.96%) of acute symptomatic stroke and convulsions within 72 h (10 cases, 37.04%) were the most common presentations. Ten patients showed no neurological symptoms and were found to have had a stroke through routine cranial ultrasonography after being hospitalized for non-neurological diseases. The risk factors include primiparity, placental or uterine abruption/acute chorioamnionitis, intrauterine distress, asphyxia, and severe infection. In the study group, 11.1% (3/27) of patients had adverse neurodevelopmental outcomes. The patients in the study group had lower scores for the ASQ than those in the control group in the communication, gross, and fine motor dimensions. Conclusion: The incidence of perinatal stroke in Beijing was consistent with that in other countries. Routine neuroimaging of infants with risk factors may enable identification of asymptomatic strokes in more patients. Patients who have suffered from a stroke may have neurological sequelae; therefore, early detection, treatment, and regular follow-ups are beneficial for improving their recovery outcomes.

Downregulation of lncRNA SNHG16 inhibits vascular smooth muscle cell proliferation and migration in cerebral atherosclerosis by targeting the miR-30c-5p/SDC2 axis.

Atherosclerosis (AS) is the basic lesion underlying the occurrence and development of cerebrovascular diseases. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in AS. We aimed to explore the role of SNHG16 in AS and the molecular mechanism of VSMC involvement in the regulation of AS. The expression levels of SNHG16, miR-30c-5p and SDC2 were detected by qRT-PCR. CCK-8, wound healing and Transwell assays were used to assess ox-LDL-induced VSMC proliferation, migration, and invasion, respectively. Western blot analysis was used to detect SDC2 and MEK/ERK pathway-related protein levels. A dual-luciferase reporter assay confirmed the binding of SNHG16 with miR-30c-5p and miR-30c-5p with SDC2. SNHG16 and SDC2 expression was upregulated in patients with AS and ox-LDL-induced VSMCs, while miR-30c-5p was downregulated. Ox-LDL-induced VSMC proliferation and migration were increased, and the MEK/ERK signalling pathway was activated. MiR-30c-5p was targeted to SNHG16 and SDC2. Downregulating SNHG16 or upregulating miR-30c-5p inhibited ox-LDL-induced VSMC proliferation and migration and inhibited MEK/ERK signalling pathway activation. In contrast, downregulating miR-30c-5p or upregulating SDC2 reversed the effects of downregulating SNHG16 or upregulating miR-30c-5p. Furthermore, downregulating SDC2 inhibited ox-LDL-induced proliferation and migration of VSMCs and inhibited activation of the MEK/ERK signalling pathway, while upregulating lncRNA SNHG16 reversed the effects of downregulating SDC2. Downregulation of SNHG16 inhibited VSMC proliferation and migration in AS by targeting the miR-30c-5p/SDC2 axis. This study provides a possible therapeutic approach to AS.