Perceptions of barriers to and facilitators of exercise rehabilitation in adults with lung transplantation: a qualitative study in China.

BACKGROUND: Exercise is crucial for pulmonary rehabilitation and improving the prognosis of lung transplantation (LTx) patients. However, many LTx patients in China have low exercise tolerance and compliance, and the reasons behind these challenges have not been fully elucidated. Therefore, this qualitative research aims to identify the barriers to and facilitators of exercise rehabilitation in LTx patients. METHODS: From January to July 2023, 15 stable LTx patients were recruited and participated in in-depth, semi-structured, face-to-face interviews at Henan Provincial People's Hospital. The interview transcripts were analyzed using the COM-B model and the Theoretical Domains Framework (TDF). RESULTS: Six general themes including 19 barriers and 14 facilitators for the exercise rehabilitation of LTx patients were identified based on the COM-B model and TDF. The barriers to exercise included physical limitations, insufficient exercise endurance, lack of knowledge, and lack of motivation. The facilitators of exercise included motivation, self-efficacy, perceived significance of exercise rehabilitation, and social support. CONCLUSION: The study offers detailed insight into the development and implementation of exercise rehabilitation intervention strategies for LTx patients. By combining COM-B model and TDF, the study provides strong evidence that active behavior change strategies are required for LTx patients to promote their participation in exercise rehabilitation. Professional support, pulmonary rehabilitation training, behavior change technology, and digital health tools are essential for strengthening the evidence system for reporting exercise efficacy and effectiveness.

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study.

BACKGROUND: The aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors. METHODS: The clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation. RESULTS: In the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma. CONCLUSIONS: Neuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

Long-term clinical efficacy of cytokine-induced killer cell-based immunotherapy in early-stage esophageal squamous cell carcinoma.

BACKGROUND AIMS: In this retrospective clinical study, the authors investigated the impact of cytokine-induced killer (CIK) cell-based immunotherapies on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 87 patients with ESCC who received comprehensive treatment were enrolled in the study. Of these patients, 43 were in the control group and 44 were in the CIK treatment group. Flow cytometry analysis was performed to detect the phenotype and anti-tumor function of CIK cells. Clinical characteristics were compared between these two groups, and the survival estimates of ESCC patients were determined using Kaplan-Meier analysis. RESULTS: CIK cells contained a high proportion of the main functional fraction (CD3+CD56+ group) and exhibited a strong killing ability for esophageal cancer cells in vitro. Importantly, overall survival (OS) and progression-free survival (PFS) were significantly higher in the CIK group than in the control group in early-stage ESCC. However, patients with advanced-stage ESCC did not benefit from CIK cell-based therapy in terms of OS and PFS compared with the control group. CONCLUSIONS: These results demonstrate that CIK cells combined with conventional treatments potentially prolong long-term survival of patients and may serve as a combined therapeutic approach for the treatment of early-stage ESCC.

Eomes promotes esophageal carcinoma progression by recruiting Treg cells through the CCL20-CCR6 pathway.

Eomesodermin (Eomes) is a T-box transcription factor that drives the differentiation and function of cytotoxic lymphocytes. However, the underlying function and mechanism of Eomes in tumor cells remains elusive. Here, we studied the role of Eomes in human esophageal squamous cell carcinoma (ESCC). Using 2 human ESCC cell lines, we found that Eomes knockdown reduced esophageal cancer cell proliferation and that the esophageal cancer cell cycle was blocked in the G2/M phase. Mechanistically, we identified CCL20 as the main downstream target of Eomes. Furthermore, we found that CCL20 could chemoregulate regulatory T cells (Tregs) through their specific receptor CCR6, then promoting the proliferation of esophageal cancer cells. Eomes knockdown also delayed the growth of human ESCC xenografts in BALB/c nude mice. Importantly, in 133 human ESCC tissues, high Eomes levels were associated with poor clinical prognosis. Overall, our findings suggested that the Eomes-CCL20-CCR6 pathway plays a vital role in human ESCC progress. Therefore, targeting this pathway may represent a promising strategy for controlling human ESCC.

A study on the information-motivation-behavioural skills model among Chinese adults with peritoneal dialysis.

AIM AND OBJECTIVE: To examine whether the information-motivation-behavioural skills model could predict self-care behaviour among Chinese peritoneal dialysis patients. BACKGROUND: Peritoneal dialysis is a treatment performed by patients or their caregivers in their own home. It is important to implement theory-based projects to increase the self-care of patients with peritoneal dialysis. The information-motivation-behavioural model has been verified in diverse populations as a comprehensive, effective model to guide the design, implementation and evaluation of self-care programmes. DESIGN: A cross-sectional, observational study. METHODS: A total of 201 adults with peritoneal dialysis were recruited at a 3A grade hospital in China. Participant data were collected on demographics, self-care information (knowledge), social support (social motivation), self-care attitude (personal motivation), self-efficacy (behaviour skills) and self-care behaviour. We also collected data on whether the recruited patients had peritoneal dialysis-associated peritonitis from electronic medical records. Measured variable path analysis was performed using mplus 7.4 to identify the information-motivation-behavioural model. RESULTS: Self-efficacy, information and social motivation predict peritoneal dialysis self-care behaviour directly. Information and personal support affect self-care behaviour through self-efficacy, whereas peritoneal dialysis self-care behaviour has a direct effect on the prevention of peritoneal dialysis-associated peritonitis. CONCLUSIONS: The information-motivation-behavioural model is an appropriate and applicable model to explain and predict the self-care behaviour of Chinese peritoneal dialysis patients. Poor self-care behaviour among peritoneal dialysis patients results in peritoneal dialysis-associated peritonitis. RELEVANCE TO CLINICAL PRACTICE: The findings suggest that self-care education programmes for peritoneal dialysis patients should include strategies based on the information-motivation-behavioural model to enhance knowledge, motivation and behaviour skills to change or maintain self-care behaviour.

Experimental and Computational Development of a Conformationally Flexible Template for the meta-C-H Functionalization of Benzoic Acids.

A conformationally flexible template for the meta-C-H olefination of benzoic acids was designed through both experimental and computational efforts. The newly designed template favors a silver-palladium heterodimer low barrier transition state, and demonstrates that it is feasible to lengthen templates so as to achieve meta-selectivity when the distance between the functional handle of the native substrate and target C-H bond decreases. Analysis of the ortho-, meta-, and para-C-H cleavage transition states determined that the new template conformation optimizes the interaction between the nitrile and palladium-silver dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds with moderate-to-good yields and generally high regioselectivity. Regioselectivity is governed exclusively by the template, and kinetic experiments reveal that there is a 4-fold increase in rate in the presence of monoprotected amino acid ligands. Using a Boltzmann distribution of all accessible C-H activation transition states, it is possible to computationally predict meta-selectivity in a number of investigated templates with reasonable accuracy. Structural and distortion energies reported may be used for the further development of templates for meta-C-H activation of hitherto unexplored arene substrates.

Purification of angiotensin I-converting enzyme (ACE) inhibitory peptides from casein hydrolysate by IMAC-Ni2.

Casein proteins were hydrolyzed by papain to identify inhibitory peptides of angiotensin I-converting enzyme (ACE). The hydrolysate was fractionized by immobilized metal affinity chromatography (IMAC-Ni2+). The fraction with high ACE inhibitory activity was enriched and further chromatographed on a reverse-phase column to yield four fractions. Among the fractions, the L4 fraction exhibited the highest ACE inhibitory activity and was identified by sequence analysis as Trp-Tyr-Leu-His-Tyr-Ala (WYLHYA), with IC50 value of 16.22 ± 0.83 µM in vitro. This peptide was expected to be applied as an ingredient for preventing hypertension and IMAC-Ni2+ may provide a simple method for purification of ACE inhibitory peptides.

Dual-emissive fluorescence measurements of hydroxyl radicals using a coumarin-activated silica nanohybrid probe.

This work reports a novel dual-emissive fluorescent probe based on dye hybrid silica nanoparticles for ratiometric measurement of the hydroxyl radical (˙OH). In the probe sensing system, the blue emission of coumarin dye (coumarin-3-carboxylic acid, CCA) immobilized on the nanoparticle surface is selectively enhanced by ˙OH due to the formation of a coumarin hydroxylation product with strong fluorescence, whereas the emission of red fluorescent dye encapsulated in the silica nanoparticle is insensitive to ˙OH as a self-referencing signal, and so the probe provides a good quantitative analysis based on ratiometric fluorescence measurement with a detection limit of 1.65 µM. Moreover, the probe also shows high selectivity for ˙OH determination against metal ions, other reactive oxygen species and biological species. More importantly, it exhibits low cytotoxicity and high biocompatibility in living cells, and has been successfully used for cellular imaging of ˙OH, showing its promising application for monitoring of intracellular ˙OH signaling events.

Water Deficit Diagnosis of Winter Wheat Based on Thermal Infrared Imaging.

Field experiments were conducted to analyze the effectiveness of the crop stress index (CWSI) obtained by infrared thermal imaging to indicate crop water status, and to determine the appropriate CWSI threshold range for wheat at different growth stages. The results showed that the sensitivity of plant physiological parameters to soil water was different at different growth stages. The sensitivity of stomatal conductance (Gs) and transpiration rate (Tr) to soil water was higher than that of leaf relative water content (LRWC) and photosynthetic rate (Pn). The characteristics of plant physiology and biomass (yield) at each growth stage showed that the plant production would not suffer from drought stress as long as the soil water content (SWC) was maintained above 57.0% of the field water capacity (FWC) during the jointing stage, 63.0% of the FWC during the flowering stage and 60.0% of the FWC during the filling stage. Correlation analysis showed that the correlation of CWSI with Gs, Tr and Pn was lower than that with LRWC and SWC at the jointing stage. CWSI was extremely significantly negatively correlated with SWC and LRWC (p < 0.01), but significantly negatively correlated with Gs, Tr and Pn (p < 0.05). At the flowering stage, CWSI was extremely significantly negatively correlated with all physiological and soil parameters (p < 0.01). The regression analysis showed that the CWSI of winter wheat was correlated with biomass (grain yield) in a curvilinear relationship at each growth stage. When the CWSI increased to a certain extent, the biomass and yield showed a decreasing trend with the increase in CWSI. Comprehensive analysis of all indexes showed that CWSI can be used as a decision-making index to guide the water-saving irrigation of winter wheat, as long as the CWSI threshold of plants was maintained at 0.26-0.38 during the jointing stage, 0.27-0.32 during the flowering stage and 0.30-0.36 during the filling stage, which could not only avoid the adverse effects of water stress on crop production, but also achieve the purpose of water saving.

Comparison of proximal and distal laparoscopic ureteroureterostomy for complete duplex kidneys in children.

OBJECTIVE: To compare efficacy of proximal and distal laparoscopic ureteroureterostomy (UU) for complete duplex kidneys in children. METHODS: Patients who underwent laparoscopic UU for complete duplex kidneys between December 2016 and July 2022 were reviewed retrospectively. 71 patients who had normal lower pole moiety without vesicoureteral reflux (VUR) were recruited. All of them underwent ultrasound, voiding cystourethrography (VCUG), renal scintigraphy, and magnetic resonance urography preoperatively. Proximal laparoscopic UU was performed in 35 patients and distal laparoscopic UU in 36 patients. Double J stents were placed in normal lower pole moieties. Clinical data, including general information, diagnosis, surgical management, imaging characteristics, clinical symptoms and postoperative complications (classified according to the modified Clavien-Dindo classification), and length of stay were recorded. Measurement date comparisons between groups were performed by t test, counting date were analyzed by chi-square test. RESULTS: The study consisted of 71 patients (56 females and 15 males) with complete duplex kidneys (41 in left kidney and 30 in right kidney). The patients' mean age was 34 m (range 3-161 m) and follow-up ranged from 25 to 81 m. No significant difference was found in age and follow-up time between the two groups. Laparoscopic UU was performed in all patients successfully. The operation time of the two groups was 108.42 ± 26.95 min for distal UU vs 121.46 ± 35.15 min for proximal UU(p = 0.14). No significant difference in postoperative complications was seen between the two groups (22.2% vs 31.4%, p = 0.345). However, in terms of the grading of postoperative complications, the proximal UU group had a higher grade (3 of them had a grade of IV) and more serious complications. CONCLUSIONS: There was no significant difference in the overall incidence of complications between distal and proximal UU. Compared with proximal laparoscopic UU, distal laparoscopic UU is easier to perform with less injury to the peripheral tissues. Postoperative complications of proximal UU are more serious and more difficult to manage. We recommend complete duplex kidney ureteral reconstruction with distal UU.

Fear of progression among postoperative patients with newly diagnosed lung cancer: a cross-sectional survey in China.

BACKGROUND: More lung cancer cases are becoming diagnosed earlier in recent years. The diagnosis is often accompanied by fear of progression (FoP). There is a clear research gap in the existing literature on FoP and the most frequent concerns in newly diagnosed lung cancer patients. OBJECTIVE: To identify the status and factors related to FoP in newly diagnosed Chinese lung cancer patients undergoing thoracoscopic lung cancer resection. METHODS: A cross-sectional design with convenience sampling was used in this study. Participants (N = 188) with newly diagnosed lung cancer (≤ 6 months) at one hospital in Zhengzhou were recruited. A demographic questionnaire, Fear of Progression Questionnaire-Short Form, Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire, and Brief Illness Perception Questionnaire were used to assess characteristics, FoP, social support, coping style, and patient illness perceptions. Multivariable logistic regression analysis was used to identify factors associated with FoP. RESULTS: The mean score of FoP was 35.39 ± 8.03. There are 56.4% of the patients (scores ≥ 34) have a clinically dysfunctional level of FoP. FoP was higher in young (18-39 years) than middle-aged patients (40-59 years) and elderly patients (≧60 years) (P = 0.004). Patients aged 40-59 years showed significantly higher fear of family-related concerns (P < 0.001), a fear of potential harm from medications (P = 0.001); Patients aged 18-39 years and 40-59 years showed significantly higher fears of work-related concerns (P = 0.012). Multiple logistic regression analyses showed that patients' age, the time from surgery and SSRS score were found to be independently associated with higher FoP. CONCLUSIONS: High FoP is a frequently reported problem among newly diagnosed lung cancer patients, especially those less than 60 years old. Professional psychoeducation, psychological interventions, and personalized support are needed for patients with a high FoP.

The bidirectional causal association between psoriasis and psychological illnesses: a 2-sample Mendelian randomization study.

There have been reports of association between psoriasis and psychological illnesses. Nevertheless, it is not easy to draw conclusions with high quality causality from conventional observational studies. The objective of this study was to evaluate the causality of psoriasis and psychological illnesses. All summary-level data from genome-wide association studies for psoriasis and psychological illnesses were collected from Neale Lab and MRC Integrative Epidemiology Unit. Bidirectional Mendelian randomization analysis was performed to determine the random orientation with an independent genetic variation. The main estimated effects are derived using Inverse-Variance Weighted, weighted median, and MR Egger methods. Multiple data sets were validated against each other, and a series of sensitivity studies were conducted to ensure the reliability of the results. Mendelian randomization analysis revealed a causal effect of psoriasis [odds ratio (OR) 1·34, 95% confidence interval (CI) 1·21-1·46, P < 0.001; and OR 1.28, CI 1.17-1.39, P < 0.001] on psychological illnesses, and vice versa (OR 1.23, CI 1.14-1.31, P < 0.001; and OR 1.21, CI 1.11-1.31, P < 0.001). The results were supported by a series of sensitivity analyses. The findings of this Mendelian randomization study support a causal effect between psoriasis and psychological illnesses, and vice versa.

Two-sample mendelian randomization reveals a causal association between membranous nephropathy and lung cancer.

A risk association between membranous nephropathy (MN) and lung cancer is reported, but traditional observational studies cannot provide strong evidence of its causality. This study aimed to assess genome-wide association studies data for a causal relationship between MN and lung cancer using a two-sample Mendelian randomization (MR) approach. Inverse-variance weighted, and MR Egger regression techniques were used to determine the association of genetic variants from cohorts of MN and lung cancer patients. Independent genetic variants with genome-wide significance (P < 5×10-8) were used to determine the direction of chance. Sensitivity analyses confirmed the accuracy of the results. The results suggest that MN is an exposure factor for lung cancer, validated using a second cohort of lung cancer patients (P < 0.001). There is insufficient evidence to suggest a causal relationship between lung cancer and MN; however, cigarette smoking may be a confounding factor for lung cancer due to MN. The findings provide causal evidence for the effect of MN on lung cancer risk and may be useful for patient management, especially in older patients with MN who should be systematically screened regularly.

Single-cell and bulk sequencing analyses reveal the immune suppressive role of PTPN6 in glioblastoma.

Glioblastoma (GBM) is a highly malignant brain cancer with a poor prognosis despite standard treatments. This investigation aimed to explore the feasibility of PTPN6 to combat GBM with immunotherapy. Our study employed a comprehensive analysis of publicly available datasets and functional experiments to assess PTPN6 gene expression, prognostic value, and related immune characteristics in glioma. We evaluated the influence of PTPN6 expression on CD8+ T cell exhaustion, immune suppression, and tumor growth in human GBM samples and mouse models. Our findings demonstrated that PTPN6 overexpression played an oncogenic role in GBM and was associated with advanced tumor grades and unfavorable clinical outcomes. In human GBM samples, PTPN6 upregulation showed a strong association with immunosuppressive formation and CD8+ T cell dysfunction, whereas, in mice, it hindered CD8+ T cell infiltration. Moreover, PTPN6 facilitated cell cycle progression, inhibited apoptosis, and promoted glioma cell proliferation, tumor growth, and colony formation in mice. The outcomes of our study indicate that PTPN6 is a promising immunotherapeutic target for the treatment of GBM. Inhibition of PTPN6 could enhance CD8+ T cell infiltration and improve antitumor immune response, thus leading to better clinical outcomes for GBM patients.

Causal association between colorectal cancer and Alzheimer's disease: a bidirectional two-sample mendelian randomization study.

Background: Colorectal cancer and Alzheimer's disease are both common life-threatening diseases in the elderly population. Some studies suggest a possible inverse relationship between colorectal cancer and Alzheimer's disease, but real-world research is subject to many biases. We hope to clarify the causal relationship between the two through a bidirectional two-sample Mendelian randomization study. Methods: In our study, we used genetic summary data from large-scale genome-wide association studies to investigate the relationship between colorectal cancer and Alzheimer's disease. Our primary analysis employed the inverse-variance weighted method and we also used complementary techniques, including MR-Egger, weighted median estimator, and Maximum likelihood. We applied simex adjustment to the MR-Egger results. We also utilized the MRlap package to detect potential sample overlap and its impact on the bias of the results. In addition, we performed several sensitivity and heterogeneity analyses, to ensure the reliability of our results. Results: The combined effect size results of the inverse-variance weighted method indicate that colorectal cancer may decrease the incidence of Alzheimer's disease, with an odds ratio (OR) of 0.846 (95% CI: 0.762-0.929). Similar results were observed using other methods such as MR-Egger, weighted median estimator, and Maximum likelihood. On the other hand, Alzheimer's disease may slightly increase the incidence of colorectal cancer, with an OR of 1.014 (95% CI: 1.001-1.027). However, the results of one subgroup were not significant, and the results from MRlap indicated that sample overlap introduced bias into the results. Therefore, the results of the reverse validation are not reliable. The F-statistic for all SNPs was greater than 20. Four SNPs related to the outcome were excluded using Phenoscanner website but the adjustment did not affect the overall direction of the results. The results of these statistics were further validated by MR-PRESSO, funnel plots, leave-one-out analyses, Cochran's Q, demonstrating the reliability of the findings. Conclusion: According to the findings of this Mendelian randomization study, there appears to be a causal association between colorectal cancer and Alzheimer's disease. These results could have important implications for clinical practice in terms of how colorectal cancer and Alzheimer's disease are treated. To better understand the relationship between these two diseases, more research and screening are needed in clinical settings.

Corrigendum: Immunogenomic landscape in breast cancer reveals immunotherapeutically relevant gene signatures.

[This corrects the article DOI: 10.3389/fimmu.2022.805184.].

Efficient delivery of the lncRNA LEF1-AS1 through the antibody LAIR-1 (CD305)-modified Zn-Adenine targets articular inflammation to enhance the treatment of rheumatoid arthritis.

BACKGROUNDS: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. METHODS: The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. RESULTS: LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1ß, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. CONCLUSIONS: LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

Dual Delivery of Tetramethylpyrazine and miR-194-5p Using Soft Mesoporous Organosilica Nanoparticles for Acute Lung Injury Therapy.

Background: The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low. Purpose: To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein. Methods: NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically. Results: In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice. Innovation: This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice. Conclusion: NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice.

Identification and functional characterization of Pomstna in Japanese flounder (Paralichthys olivaceus).

Myostatin (MSTN) as a negative regulator of muscle growth has been identified in Japanese flounder. Yet, most fish experienced the teleost specific genome duplication and possess at least two mstn genes. In current study, the second mstn gene named Pomstna is identified in Japanese flounder. Pomstna is clustered with other mstn2 of teleosts and owned highly conserved TGF-beta domain. In addition to muscle, Pomstna also highly expressed in brain and spleen. Using the primarily cultured muscle cells of Japanese flounder, we found that Pomstna could inhibit the proliferation and differentiation of muscle cells in vitro. As a ligand of TGF-beta signaling pathway, Pomstnb could regulate the expression of p21 and myod by activating the TGF-beta signaling pathway. Different from the function of Pomstnb, Pomstna could not activate the TGF-beta signaling pathway in vitro. During the differentiation of PoM cells, the expression of Pomstnb decreased significantly but the expression of Pomstna showed no change. Our study suggests that Pomstna could negatively regulate the growth and differentiation of muscle like Pomstnb yet through a different regulatory mechanism than Pomstnb. The present study suggests that muscle proliferation and differentiation were regulated by mstn not only through the TGF-beta signaling pathway but also other unknown mechanisms.

Bergamottin protects against LPS-induced endotoxic shock by regulating the NF-κB signaling pathway.

Bergamottin is a natural furanocoumarin compound that possesses antioxidative and anti-cancer properties; however, the effect of Bergamottin on lipopolysaccharide (LPS)-induced inflammation response is unknown. In this study, we investigated the protective effects and mechanisms of Bergamottin against LPS-induced inflammatory responses.Raw264.7 cells were pre-treated with Bergamottin, then stimulated with LPS. Morphologic analysis and flow cytometry were used to measure Bergamottin-related cytotoxicity. ELISA and qPCR were performed to measure secretion and transcription activities of inflammatory cytokines. Biochemical analysis was used to determine the expression of tissues damage indicators. Western blots were used to determine protein expression, and immunofluorescence staining was used to determine the co-localization of NF-κB and RelA. Hematoxylin and eosin staining was used to show the pathological damages.Bergamottin had no cytotoxic effects on Raw264.7 cells. Pre-treatment with Bergamottin inhibited inflammatory cytokines expression and secretion induced by LPS, due to the inhibition of LPS-induced NF-κB signaling pathway activation, and improved pathological damages. These findings suggest that Bergamottin protects against LPS-induced endotoxin shock by regulating the NF-κB signaling pathway.