Milk-derived small extracellular vesicles: a new perspective on dairy nutrition.

Milk contains bioactive compounds that have multiple essential benefits. Milk-derived small extracellular vesicles (M-sEVs) have emerged as novel bioactive milk components with various beneficial biological functions and broad applications. The M-sEVs from different mammalian sources have similar composition and bioactive functions. The digestive stability and biocompatibility of the M-sEVs provide a good foundation for their physiological functions. Evidence suggests that M-sEVs promote intestinal, immune, bone, neural, liver, and heart health and show therapeutic effects against cancer, indicating their potential for use in functional foods. In addition, M-sEVs can be developed as natural delivery carriers owing to their superior structural characteristics. Further studies are needed to elucidate the relationship between the specific components and functions of M-sEVs, standardize their extraction processes, and refine relevant clinical trials to advance the future applications of M-sEVs. This review summarizes the structure and composition of M-sEVs isolated from different milk sources and discusses several common extraction methods. Since the introduction of M-sEVs for digestion and absorption, studies have been conducted on their biological functions. Furthermore, we outline the theoretical industrial production route, potential application scenarios of M-sEVs, and the future perspectives of M-sEV research.

Effects of hydrocolloids as fat-replacers on the physicochemical and structural properties of salt-soluble protein isolated from water-boiled pork meatballs.

Konjac glucomannan (KGM), xanthan gum (XG), guar gum (GG), and κ-carrageenan (KC), as substituent, are commonly used in ground pork products. Here, the content of these (0.5, 1.0, 1.5, and 2.0%, w/w) on the gel properties, thermal properties, and interaction forces of salt-soluble protein (SSP) isolated from water-boiled pork meatballs were investigated. We found 1.0% KGM, 0.5% XG, 0.5-2.0% GG, and 0.5-2.0% KC to water-boiled pork meatballs exerted a positive effect on the denaturation temperature, hydrogen bonds, hydrophobic interactions, disulfide bonds, α-helix, and ß-sheet content of SSP, as well as the strength and storage modulus of the modified protein gel. The addition of these hydrocolloids with the addition of 1.0% aggregated myosin and actin, led to the enhancement of the bands corresponding to myosin heavy chain and actin. The prediction model of gel strength showed that the gel strength was negatively correlated with Tpeak1, Tpeak2, and ionic bond. This study provides theoretical guidance for improving the application of hydrocolloids in pork-based foods.

Effect of Microwave Vacuum Freeze-Drying Power on Emulsifying and Structure Properties of Egg White Protein.

The study investigated the effects of different microwave vacuum freeze-drying powers (100-500 W) on the emulsifying properties and structural characteristics of egg white protein, which is of great significance in enhancing the added value of EWP and promoting its application. Emulsification analysis revealed that the emulsification performance was significantly influenced by microwave power and reached its maximum at 300 W. Fourier-transform infrared spectroscopy (FT-IR) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses showed that microwave vacuum freeze-drying treatment altered the secondary structure of EWP without changing its peptide structure. Fluorescence measurements indicated that the maximum fluorescence emission intensity decreased, and the maximum emission wavelength shifted towards blue as the power increased. Particle size, zeta potential, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) analyses showed that the average particle size of EWP reached the minimum value of 1203.66 nm, the absolute value of zeta potential reached the maximum value of 41.35 mV, and the thermal stability was strongest, with a more uniform and loose structure observed at 300 W. Texture profile analysis (TPA) showed that appropriate power treatment significantly enhanced the chewiness and viscoelasticity of egg white protein. Therefore, appropriate power treatment could effectively improve the emulsifying properties and stability.

MFGM components promote gut Bifidobacterium growth in infant and in vitro.

PURPOSE: Infant gut microbiota which plays an important role in long-term health is mainly shaped by early life nutrition. However, the effect of nutrients on infants gut microbiota is less researched. Here, we present a study aiming to investigate in vitro a modified formula that is supplemented with milk fat globule membrane (MFGM) that were missing in common formulas when compared with human milk and to assess the impact of feeding scheme on microbiota and metabolism. METHODS: A total of 44 infants including 16 from breast milk feeding, 13 from common formula feeding and 15 from modified formula feeding were analyzed, and A cross-sectional sampling of fecal and urine was done at 1 month-of-age. Stool microbiota composition was characterized using high-throughput DNA sequencing, and urinary metabolome was profiled by nuclear magnetic resonance (NMR). In vitro growth experiment of Bifidobacterium with key components from MFGM was performed and analyzed by both DNA and RNA. RESULTS: Stool samples from the infants who were breastfed had a higher relative abundance of Bifidobacterium and a lower relative abundance of Escherichia than the formula-fed infants. The stool microbiome shifts were associated with urine metabolites changes. Three substances including lactadherin, sialic acid and phospholipid, key components of MFGM were significantly positively correlated to Bifidobacterium of stool samples from infants, and stimulated the growth rate of Bifidobacterium significantly by provided energy in vitro growth experiment with RNA analysis. CONCLUSIONS: These findings suggest that the key components from MFGM could improve infants' health by modulating the gut microbiome, and possibly supporting the growth of Bifidobacterium. REGISTRATION: Clinicaltrials.gov NCT02658500 (registered on January 20, 2016).

The Role of Experience and Gender in Founders' Business Planning Activities: A Meta Analysis.

The question of why entrepreneurs undertake business planning activities differently, ranging from planning "in the head" to generating formal written documents, is still impenetrable. Aggregating data on 11,064 observations from 32 independent data set, this study meta-analyzed how business experience and gender influence entrepreneurs' disposition to business planning behaviors. Surprisingly, contradictory to some extant views that entrepreneurs without prior experience are more likely to make business plans, we found that both managerial experience and entrepreneurial experience positively influence entrepreneurs' subsequent business planning behaviors. Drawing insight from the effectuation and institutional perspectives, this study showed that, rather than entrepreneurial experience, managerial experience motivates entrepreneurs to generate formal business plans. For entrepreneurs who create formal business plans, both entrepreneurial experience and managerial experience enhance their business planning sophistication. In addition, we examined the moderating effects of gender on the relationship between business experience and business planning. The results suggested that female entrepreneurs with entrepreneurial experience are more likely to undertake business planning behaviors and create formal business plans than their male counterparts.

A case report of right upper lung adenosquamous carcinoma resection following neoadjuvant targeted therapy.

The patient was a middle-aged male smoker who had space-occupying lesions in the right upper lung, Positron emission tomography-computed tomography (PET-CT) suggested right upper lung cancer with multiple mediastinal lymph node metastases. Endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-GS-TBLB) performed in the bronchus of the right apical segment confirmed the lesion as squamous cell carcinoma. Neoadjuvant therapy was planned. Because genetic testing revealed the epidermal growth factor receptor (EGFR) L858R mutation, the possibility of adenosquamous carcinoma was considered. The patient was clinically diagnosed with right upper lung squamous cell carcinoma c-T3N2M0, stage IIIB, and PS 1 point. Dacomitinib was selected for the targeted therapy. Eight weeks after the initiation of treatment, efficacy was assessed as a partial response (PR), suggesting a possibility of R0 resection. After sufficient communication with the patient and his family members, on July 1, 2020, thoracoscopic radical resection of the right upper lung cancer was performed under general anesthesia. Postoperative pathology confirmed adenosquamous carcinoma, of which 80% were adenocarcinoma and 20% were squamous cell carcinoma; no tumor thrombus was seen in the interstitial vessels; and the tumor did not invade the visceral pleura. There was no cancerous infiltration in the bronchial stump of the right upper lung. The following were the results for lymph nodes submitted for examination: L2 (0/1), L4 (0/4), L7 (0/3), L8 (0/7), L10 (0/1), L11 (0/2) and L11 (frozen 0/1) showed no cancer metastasis. The postoperative diagnosis was as follows: adenosquamous carcinoma of the right upper lung p-T2N0M0, stage Ib. After surgery, 4 cycles of the GC (gemcitabine + carboplatin) chemotherapy regimen were given, with continued targeted therapy recommended for 2 years. The patient has been followed-up and is in good condition.

Green research and development activities and SO2 intensity: an analysis for China.

Carrying out domestic research and development (R&D) activities can improve environmental performance. However, extant studies have not conclusively indicated that R&D activities in all energy fields lead to a reduction in the SO2 intensity. SO2 intensity is defined as the ratio of SO2 emissions to the GDP. Hence, green R&D activities are required. However, the strong heterogeneity between green R&D activities could have distinctive economic consequences. Thus, it is imperative to study the heterogeneity of green R&D activities on SO2 intensity. Moreover, previous studies have ignored regional differences. Although overlooked in the literature, a technology's adsorptive ability could be a key determinant of the effects of green R&D activities on SO2 intensity. Based on a linear analysis of China's provincial data over 2000-2016, we show that green R&D activities are instrumental in reducing SO2 intensity. Different green R&D activities have distinct goals and contrasting statistical effects on SO2 intensity. The empirical results show that the impact of green R&D activities on SO2 intensity differs by region. Lastly, it is proposed that green R&D activity effects on SO2 intensity are nonlinear by analysing a technology's adsorptive ability.

Concomitant lung adenocarcinoma and pulmonary cryptococcosis confirmed by pathologic examinations.

To describe the characteristics of concomitant lung cancer and pulmonary cryptococcosis (PC) cases.A total of 8 patients with lung cancer and coexisting PC, who were admitted to Fuzhou Pulmonary Hospital of Fujian from 1st January 2009 to 31st December 2015 and whose diagnoses were confirmed by pathological examinations, were studied.One patient had a history of diabetes mellitus and 1 had a history of treated with surgery. The lesions in 7 cases manifested as nodular shadows; only 1 case showed the lesion of the 2 diseases mergedmixed together, and it manifested as a large flake-like infiltrated shadow in the same lobe. The histological type in all of the patients was lung adenocarcinoma. Lung cancer stage was advanced (III-IV) in 25.0% of the cases. The 5 patients who received surgery and drug treatment are presently healthy following resection. Recurrence and metastasis of lung cancer following surgery occurred in 2 patients in whom the tumor was controlled again after anti-tumor treatment. One patient with advanced lung cancer and PC was treated with antifungal therapy in combination with antineoplastic chemotherapy, but she failed to improve and died 10 months after symptom onset during the follow-up period.PC coexisting with pulmonary carcinoma is rare. PC can manifest as pulmonary nodules and mimic malignant lesions, so it must be considered during a differential diagnosis of pulmonary nodules, especially in immunosuppressed patients.

First successful combination of extracorporeal membrane oxygenation (ECMO) with video-assisted thoracic surgery (VATS) of pulmonary bullae resection in the management of refractory pneumothorax in a critically ill patient with H7N9 pneumonia and acute respiratory distress syndrome: A case report.

RATIONALE: At present, data regarding refractory pneumothorax treated with video-assisted thoracic surgery (VATS) in combination with extracorporeal membrane oxygenation (ECMO) in critically ill patients with H7N9 pneumonia have never been reported. PATIENT CONCERNS: A laboratory-confirmed case of human infection with avian influenza A (H7N9) virus was treated in our hospital. Acute respiratory distress syndrome (ARDS) developed and the patient was oxygenated via veno-venous ECMO due to the failure of mechanical ventilation. Unfortunately, a right refractory pneumothorax occurred. Despite treatment with pleural drainage and select bronchial occlusion, the patient still failed to improve. DIAGNOSIS: Fatal H7N9 pneumonia complicated with severe ARDS, pulmonary bullae, and refractory pneumothorax. INTERVENTIONS: Successful combination of ECMO with VATS of pulmonary bullae resection was performed and pneumothorax was cured. OUTCOMES: One week after the operation, ECMO was removed. However, the patient finally developed multiorgan failure (MOF) complicated by refractory hypoxemia due to progressive lung fibrosis and died 36 days after admission. LESSONS: Although the patient died of MOF triggered by severe lung fibrosis at last, the successful treatment of refractory pneumothorax by combination of ECMO with VATS is encouraging. Thus, when refractory pneumothorax in a patient with severe pulmonary dysfunction fails to improve through routine therapy, the treatment of pneumothorax by VATS based on ECMO support can be considered as a feasible selection.

The convergence characteristics of China's carbon intensity: Evidence from a dynamic spatial panel approach.

In recent years, China's CO2 emissions have surged as the country's economy has expanded rapidly. Faced with mounting international and domestic pressures, China has made great efforts to curb CO2 emissions. To formulate targeted regional reduction plans, the features and characters of provincial carbon intensity should be carefully evaluated. In this study, the existence of convergence in China's carbon intensity and possible technological factors that may influence the convergence, are carefully investigated by building a united framework and employing dynamic spatial panel approach. The estimation results verify that there is significant spatial correlation in China's provincial carbon intensity. There is also evidence that the three different types of convergence (i.e., stochastic convergence, σ-convergence and ß-convergence) exist during the sample period of 2000-2016. Moreover, among the technological factors of conditional ß-convergence, indigenous innovation activity is most critical. Not all foreign innovations stem from the inflow of foreign direct investment and trade exert a positive effect on carbon intensity reduction. Besides, it is estimated that the spatial spillovers effects from neighboring provinces are important to carbon intensity.

Thermal instability and characteristics of donkey casein micelles.

The thermal stability of donkey milk, which largely depends on the stability of casein and whey proteins, plays a critical role in the manufacture of donkey dairy products. However, the thermal stability of donkey casein micelles is poorly understood. Our study first found that donkey milk exhibited poor thermal stability, with sedimentation observed after heating at 75 °C for 10 min. Moreover, electrophoresis results indicated that donkey casein micelles were more sensitive to heat treatment than whey protein. The characteristics of donkey casein micelles were then studied to determine the thermal instability mechanism. Donkey casein micelles had a larger diameter (295 ±â€¯11 nm) and lower absolute zeta potential (-15.4 ±â€¯0.5 mV) than bovine casein micelles, mainly due to their very low κ-casein levels. The higher proportion (51%) of ß-casein in donkey casein micelles made them less hydrated. Furthermore, <40% of calcium in donkey milk was associated with donkey casein micelles. To eliminate the influence of whey protein, micellar casein was isolated from skim donkey milk by ultracentrifugation and then redispersed in its ultrafiltrate. Transmission electron microscopy and particle size analysis showed the extensive aggregation of isolated casein micelles after thermal treatment, which confirmed the thermal instability of casein micelles observed in donkey milk. Overall, poor colloidal stability and a high­calcium environment largely contributed to the thermal instability of donkey casein micelles.

Differential gene expression profile analysis in corticosterone-treated PC12 cells.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that has been ranked as the 4th leading cause of disability worldwide. Past clinical and laboratory evidence has confirmed that abnormalities of the hypothalamic-pituitary-adrenal (HPA)-axis are involved in MDD development. In this study, we took advantage of corticosterone treatment of PC12 cells as a model to identify genes regulated by HPA-axis hormones. Next-generation RNA-Seq technology was utilized to explore genome-wide differentially expressed gene profiles between control and corticosterone treated PC12 cells. 1,274 genes with at least two-fold expression level change were identified. Gene ontology analysis showed that the top enriched biological processes included response to glucocorticoid signaling, apoptosis, cell division/DNA replication, and neuron projection/axon guidance, highly consistent with phenotypes of PC12 cells treated with corticosterone. Taken together, RNA-seq data is reliable and comprehensive, thus providing a valuable resource for understanding underlying mechanisms of glucocorticoid-induced neuron malfunction.

The stress response HPA-axis hormone, glucocorticoid, reduces cellular SKA complex gene expression.

The Spindle- and Kinetochore-Associated (SKA) complex has been proven to be involved in many human mental behavioral disorders. Glucocorticoid, a hypothalamic-pituitary-adrenal (HPA) axis hormone, is a critical mediator of stress response in neurons. However, the underlying mechanisms of glucocorticoid's effects on human neuronal cells remain unclear. This study demonstrates that increased extracellular glucocorticoid levels significantly reduce neuronal cell SKA complex genes' expression levels, followed by altered neuronal cell viability and neurite development. The results suggest that the abnormality of this HPA-axis hormone could impact the neuronal cell functions through the alternation of SKA complex functions, which might induce cell death.

Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3ß/ß-catenin signaling pathways.

Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 µmol/L, respectively. At low concentrations (1-5 µmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3ß and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3ß/ß-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

Histopathological findings in a critically ill patient with avian influenza A (H7N9).

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23(rd) day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient's clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39(th) day after symptom onset, despite corticosteroid treatment.