The relationship between health-promoting behaviors and negative emotions in college freshmen: a cross-lagged analysis.

Background: The prevalence of mental health issues has been gradually increasing among college students in recent years. Improvements in mental health can be achieved through changes in daily behavior and the use of psychological counseling. This study aims to investigate the relationship between health-promoting behaviors and negative emotions among college freshmen as they enter the university. It also examines the impact of various sub-dimensions of health-promoting behaviors and other factors on the negative emotions (stress, anxiety, and depression) experienced by college freshmen. Methods: Using the Negative Emotion and Health-Promoting Behavior scales, a 7-month longitudinal study was conducted on 4,252 college freshmen, with collection of data at two time points (T1: November 12, 2021; T2: June 17, 2022). Out of this longitudinal study, 3,632 valid samples were obtained. This research aimed to explore the association and impact between negative emotions and the level of health-promoting behaviors among college students during their time at the university. Results: ① There were significant differences in the levels of health-promoting behaviors and negative emotions over the course of 7 months (P < 0.05). Health-promoting behaviors were found to have a significant negative correlation with negative emotions (P < 0.05). ② Negative emotions at T1 significantly negatively predicted health-promoting behaviors at T2 (ß = -0.11, P < 0.01), while health-promoting behaviors at T1 significantly negatively predicted negative emotions at T2 (ß = -0.12, P < 0.001). ③ Stress management (ß = -0.104, P < 0.05; ß = -0.087, P < 0.05), self-actualization (ß = -0.282, P < 0.01; ß = -0.260, P < 0.05), health responsibility (ß = -0.057, P < 0.05; ß = -0.088, P < 0.05), and interpersonal relations (ß = 0.068, P < 0.01; ß = 0.138, P < 0.05) were important components in improving stress and anxiety. Self-actualization (ß = -0.437, P < 0.001), exercise (ß = 0.048, P < 0.001), nutrition (ß = 0.044, P < 0.001), and interpersonal relations (ß = 0.065, P < 0.001) were important components in improving depression. ④ Gender, place of household registration, and whether the individual is the only child were significant factors affecting negative emotions in college freshmen. Conclusion: The level of health-promoting behaviors is an important indicator for assessing the negative emotional states of college freshmen. Enhancing health-promoting behaviors across various dimensions can help alleviate different types of negative emotions. Gender, place of household registration, and being the only child are significant factors that influence negative emotions.

Double Level Knee Derotational Osteotomy Yields Better Postoperative Outcomes than Tibial Tubercle Transfer Combined with Medial Patellofemoral Ligament Reconstruction in Patients with Recurrent Patellar Instability and Severe Malrotation.

PURPOSE: To assess the postoperative outcomes of double level knee derotational osteotomy (KDRO) combined with medial patellofemoral ligament reconstruction (MPFLR), and to compare it with tibial tuber transfer (TTT) and MPFLR without derotational osteotomy in patients with recurrent patellar instability (RPI) and a marked torsional deformity. METHODS: From March 2020 to December 2021, patients with torsion deformity (combined femoral torsion and tibial torsion ≥ 30°) were retrospectively included. The minimum follow-up time was 18 months. Patients received KDRO and MPFLR were categorized into KDRO group and patients received a combined TTT and MPFLR were categorized into control group. Preoperative and postoperative clinical symptoms, patient-reported outcomes (PROs) (Kujala, visual analogue scale [VAS], Lysholm, International Knee Documentation Committee [IKDC], Tegner, and Knee Injury and Osteoarthritis Outcome [KOOS] scores) and imaging parameters (femoral torsion, tibial torsion, patellar height, femoral trochlear dysplasia, congruence angle, patellar tilt angle, lateral patellar angle, lateral patellar translation, and tibial tubercle-trochlear groove distance) were analyzed. RESULTS: In all, 36 patients were included with 18 in KDRO group and 18 in control group. The mean follow-up time was 30 (range 21-39) months. At the latest follow-up, no patient experienced re-dislocation in either group. Except for the femoral torsion and tibial torsion in the control group, postoperative imaging parameters were significantly reduced to the normal range. KDRO group has a lower patellar tilt angle (P=.043, effect size 0.64). All clinical scores in both groups significantly improved postoperatively. KDRO group has better functional scores than control group except the KOOS daily living activities subscore and the KOOS sports and recreation subscore. More proportions of patients in KDRO group met the minimal clinically important difference (MCID) for most PROs than control group. Eight patients (44%) in the control group complained of postoperative anterior knee pain, compared with 1 patient (6%) in KDRO group (P=.018). CONCLUSION: KDRO combined with MPFLR was associated with better postoperative outcomes than TTT combined with MPFLR in patients with RPI and a torsion deformity.

Trends of Low Back Pain Research in Older and Working-Age Adults from 1993 to 2023: A Bibliometric Analysis.

Although the number of publications focusing on low back pain in older adults (LBP-O) and working-age adults (LBP-W) has been growing for decades, comparative research trends in these two populations, which may help to guide future investigation, have not been rigorously explored. This analysis aimed to describe publication patterns and trends of research targeting LBP-O and LBP-W over the last three decades. Peer-reviewed LBP-O and LBP-W articles published between 1993 and 2023 were retrieved from the Web of Science, which provided the details of annual publication volume, and prominent journals/countries/institutions. The relationship between the annual publication volumes and years was analyzed by Spearman correlation analysis. The hot topics and emerging trends were analyzed by VOSviewer and CiteSpace, respectively. A total of 4217 LBP-O-related and 50,559 LBP-W-related documents were included. The annual publication volumes of LBP-O and LBP-W articles increased over the years (r=0.995 to 0.998, p<0.001). The United States had the highest number of prominent institutions publishing relevant articles. The most prolific journal for LBP-O (5.4%) and LBP-W-related (6.1%) papers is the journal "Spine". Cognitive behavioral therapy, intervertebral disc (IVD) degeneration, physiotherapy, physical activity, and walking were the recent hot topics and physical activity was an emerging trend in LBP-O, while surgery and IVD degeneration (also a hot topic) were emerging trends in LBP-W. This study highlights the paucity of LBP-O-related research in the past. The United States and the journal Spine stand out in LBP research. The research trend of physical activity in LBP-O is consistent with the recognized importance of physical activity for older adults in general, and for managing LBP-O in particular. Conversely, the emerging trends of surgery and intervertebral disc degeneration in LBP-W research highlight a focus on the biomedical model of LBP despite LBP being a biopsychosocial condition.

Fibronectin promotes tumor progression through integrin αvß3/PI3K/AKT/SOX2 signaling in non-small cell lung cancer.

The tumor microenvironment, especially the extracellular matrix (ECM), is strongly associated with tumor cell proliferation and metastasis. Numerous studies have provided evidence suggesting that fibronectin (FN) in ECM supports cancer cell escape and contributes to cell migration, resulting in distant cancer metastasis and poor outcomes in patients. In our study, it was demonstrated that FN expression was elevated in tumor tissues from highly malignant NSCLC patients, compared to those with low malignancy (p = 0.0076). Importantly, FN promoted proliferative phenotypes and strengthened tumorigenesis capabilities in NSCLC cells, including A549 and Lewis cells, leading to sustained tumor growth in vivo. Mechanistically, it was identified that FN facilitated the activation of the integrin αvß3/PI3K/AKT signaling pathway, which subsequently upregulated tumor stemness through the downstream transcription factor SOX2. Blockade of integrin αvß3 signal efficiently suppressed NSCLC proliferation and tumorigenesis both in vitro and in vivo. In conclusion, our study demonstrated that extracellular FN could facilitate NSCLC development through the integrin αvß3/PI3K/AKT/SOX2 signaling pathway. Blockade of integrin αvß3 could efficiently enhance the anticancer effects of chemotherapy, offering an innovative approach for clinical NSCLC therapy.

METTL3 achieves lipopolysaccharide-induced myocardial injury via m6A-dependent stabilization of Myh3 mRNA.

Septic cardiomyopathy (SCM) was an important pathological component of severe sepsis and septic shock. N6-methyladenosine (m6A) modification was a common RNA modification in both mRNA and non-coding RNAs and was proved to be involved in sepsis and immune disorders. Therefore, the purpose of this study was to investigate the role and mechanism of METTL3 in lipopolysaccharide-induced myocardial injury. We firstly analyzed the expression changes of various m6A-related regulators in human samples in the GSE79962 data and the Receiver Operating Characteristic curve of significantly changed m6A enzymes, showing that METTL3 had a high diagnostic ability in patients with SCM. Western blotting confirmed the high expression of METTL3 in LPS-treated H9C2 cells, which was consistent with the above results in human samples. In vitro and in vivo, the deficiency of METTL3 could improve the cardiac function, cardiac tissue damage, myocardial cell apoptosis and reactive oxygen species levels in LPS-treated H9C2 cells and LPS-induced sepsis rats, respectively. In addition, we obtained 213 differential genes through transcriptome RNA-seq analysis, and conducted GO enrichment analysis and KEGG pathway analysis through DAVID. We also found that the half-life of Myh3 mRNA was significantly reduced after METTL3 deletion and that Myh3 carried several potential m6A modification sites. In conclusion, we found that downregulation of METTL3 reversed LPS-induced myocardial cell and tissue damage and reduced cardiac function, mainly by increasing Myh3 stability. Our study revealed a key role of METTL3-mediated m6A methylation in septic cardiomyopathy, which may offer a potential mechanism for the therapy of septic cardiomyopathy.

Thermal plasma vitrification treatment of oil-based drill cuttings: Product characterization and harmless transformation.

Oil-based drill cuttings (OBDCs) are hazardous wastes associated with the process of oil and gas extraction. In this paper, OBDCs were treated using a self-designed plasma vitrification system. The basic physicochemical properties of the OBDCs were analyzed, followed by a plasma vitrification mechanism investigation of the OBDCs. The environmental pollution risk of the vitreous slags obtained from thermal plasma treatment was also evaluated with the heavy metal extraction toxicity procedure. The batch of vitreous slags with an average glass phase content of 98.60% had a dense and smooth surface and an oxygen-to-silicon (O/Si) ratio ranging from 3.68 to 4.32, according to the findings. The melting temperature and treatment duration have a great effect on the loss ratio on acid dissolution. The leaching concentrations of Pb and Zn were 0.0004 mg/L and 0.068 mg/L, respectively, consistent with the chlorination reaction promoted by thermal plasma. Fourier transform infrared spectroscopy analysis showed that there was no organic matter in the vitreous slag, achieving the goal of harmless transition. The specific energy consumption of vitreous slags was predicted and verified by response surface methodology (RSM). This study describes the vitrification process and harmless treatment of OBDCs by thermal plasma technology, and vitreous slags have great potential for resource utilization.

Modified Nuss procedure for the treatment of pectus excavatum: Experience of 259 patients.

BACKGROUND: Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. METHODS: Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. RESULT: Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. CONCLUSION: From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.

Comprehensive plasma metabolomics and lipidomics of benign and malignant solitary pulmonary nodules.

INTRODUCTION: Solitary pulmonary nodules (SPNs) are commonly found in imaging technologies, but are plagued by high false-positive rates. OBJECTIVE: We aimed to identify metabolic alterations in SPN etiology and diagnosis using less invasive plasma metabolomics and lipidomics. METHODS: In total, 1160 plasma samples were obtained from healthy volunteers (n = 280), benign SPNs (n = 157) and malignant SPNs (stage I, n = 723) patients enrolled from 5 independent centers. Gas chromatography-triple quadrupole mass spectrometry (GC‒MS) and liquid chromatography-Q Exactive Hybrid Quadrupole-Orbitrap mass spectrometry (LC‒MS) were used to analyze the samples for untargeted metabolomics and lipidomics. RESULTS AND CONCLUSION: GC‒MS-based metabolomics revealed 1336 metabolic features, while LC‒MS-based lipidomics revealed 6088 and 2542 lipid features in the positive and negative ion modes, respectively. The metabolic and lipidic characteristics of healthy vs. benign or malignant SPNs exhibited substantial pattern differences. Of note, benign and malignant SPNs had no significant variations in circulating metabolic and lipidic markers and were validated in four other centers. This study demonstrates evidence of early metabolic alterations that can possibly distinguish SPNs from healthy controls, but not between benign and malignant SPNs.

Combined nature and human selections reshaped peach fruit metabolome.

BACKGROUND: Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear. RESULTS: Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders' and consumers' preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5. CONCLUSIONS: This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.

Identification of key gene networks controlling anthocyanin biosynthesis in peach flower.

Flavonoids, particularly anthocyanin is the main pigment that determined the red color of peach flowers, and help the plant to attract pollinators, protect the reproductive organs of flower from photo-oxidative effects of light and various non-communicable diseases. Through weightage gene coexpression network analysis (WGCNA) we identified a network of 15 hub genes that co-expressed throughout peach flower development including 5 genes coded for the key enzymes (CHI, F3'H, DFR, LAR and UFGT) of flavonoid biosynthetic pathway and 1 gene Prupe.1G111700 identified as R2R3 family transcription factor MYB108. Over expression of PpMYB108 significantly increased anthocyanin biosynthesis in Tobacco flowers. Moreover, the expression correlation between PpMYB108 and PpDFR, suggests that PpMYB108 play the role of transcriptional activator for PpDFR. This was further supported by a 6 bp insertion of MYB biding site in the core promoter region of PpDFR in red flower. The positive interaction of PpMYB108 with PpDFR promoter from red flower was confirmed in yeast one hybrid assay. These findings may be helpful in peach breeding programs as well as in identifying anthocyanin related genes in other species.

Benefits of Exergame Training for Female Patients With Fibromyalgia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the effects of exergame training on female patients with fibromyalgia syndrome (FMS). Outcome measurements mainly include overall functioning, pain perception, quality of life, exercise capacity, health perception, kinesiophobia, and fatigue severity. DATA SOURCES: Five electronic databases (PubMed, Web of Science, PsycInfo, Scopus, and Cochrane Library) were searched from inception until June 24, 2021. In addition to searches, review the reference lists of relevant papers by hand was also conducted. Cochrane Collaboration's tool for assessing risk of bias was used to evaluate the risk of bias in the included studies. STUDY SELECTION: Articles were collected with the following study inclusion criteria: (1) randomized controlled trial (RCT) design; (2) participants were female patients with FMS aged older than 18 years; (3) participants in experimental groups received exergame training using any modality; and (4) outcome measures included overall functioning, quality of life, exercise capacity, health perception, kinesiophobia, and fatigue severity. DATA EXTRACTION: The data were independently extracted by 2 researchers. The extracted data related to the document characteristics (first author, publication year, and country) participant characteristics (number and age of participants in the experimental and control groups), and interventions (intervention content, frequency, and duration, and measurement tools). DATA SYNTHESIS: Nine RCTs including 466 female patients with FMS were included in the analysis. Exergame training had significant positive effects on overall functioning (standardized mean difference [SMD], -0.52; 95% confidence interval [CI], -0.77 to 0.27; P<.0001), pain perception (SMD, -0.49; 95% CI, -0.97 to -0.02; P=.04), quality of life (SMD, 0.77; 95% CI, 0.44-1.10; P<.00001), exercise capacity (SMD, 0.58; 95% CI, 0.32-0.84; P<.0001), health perception (SMD, 0.69; 95% CI, 0.38-1.01; P<.0001), and fatigue severity (SMD, -0.97; 95% CI, -1.55 to -0.38; P=.001). However, exergame training did not have significant effects on kinesiophobia (SMD, -1.13; 95% CI, -2.88 to 0.62; P=.21). CONCLUSIONS: Exergame training has beneficial effects on the overall functioning, pain perception, quality of life, exercise capacity, health perception and fatigue severity of female patients with FMS. Exergame training is a potential non-drug therapy for the treatment of patients with FMS.

A Clinical Study Investigating Whether the Tongue-Out Position Improves the Quality of the Anatomical Appearance of the Pharynx on CT Imaging.

Objective: To evaluate the effect of using the tongue-out position on the quality of the anatomical appearance of the pharynx on computed tomography (CT) images. Methods: The data from enhanced CT thin-section images of the head and neck in 119 cases scanned were retrospectively analyzed. The cases were divided into two groups based on the position of the tip of the tongue on the images: the tongue-out group (63 cases) and non-tongue-out group (56 cases). Two observers separately evaluated the anatomy of the soft palate, uvula, palatine tonsils, epiglottis, epiglottic fossa, pyriform fossa, arytenoid folds, and tongue on all images. The Kappa test was applied to assess the consistency of scores between the two observers. In the case of data that satisfied the normal distribution, the significance of the difference in the average scores between the two groups was tested using an independent samples t-test with a value of p > 0.05. In the case of data that did not satisfy the normal distribution, the Mann-Whitney U test was adopted to test the significance of the difference in the average scores between the two groups using a value of p < 0.05. The number of cases with swallowing artifacts on the CT images in both groups was statistically analyzed and the chi-square test was used to determine whether the difference in the incidence of artifacts between the two groups was significant. Results: The Kappa test showed good consistency between the two observers scoring of the soft palate, uvula, epiglottis, epiglottic fossa, pyriform fossa, aryepiglottic folds, and tongue. The image scores of the soft palate, uvula, epiglottis, epiglottic fossa, and tongue in the tongue-out group vs. the non-tongue-out group did not satisfy the normal distribution. The Mann-Whitney U test showed that the differences in the image scores between the two groups were statistically significant in all cases (p < 0.05). The incidence of swallowing artifacts in the tongue-out group and the non-tongue-out group was 15 and 32%, respectively. The result of the chi-square test showed that the difference in the incidence of swallowing artifacts between the two groups was statistically significant (p = 0.037). Conclusion: The tongue-out position facilitated an improvement in the CT appearance of pharyngeal anatomy and was associated with a reduction in the incidence of swallowing artifacts.

The effects of myofascial release technique for patients with low back pain: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this meta-analytic review was to quantitatively examine the effects of myofascial release technique (MFR) on pain intensity, back disability, lumbar range of motion, and quality of life in patients with low back pain (LBP). METHODS: Potential articles were retrieved using five electronic databases (Web of Science, PubMed, Scopus, China National Knowledge Infrastructure, and Wanfang). The search period was from inception to January 27, 2021. Two researchers independently completed record retrieval and selection, data extraction, and methodological quality assessment. Randomized controlled trials (RCTs) assessing the effect of MFR on pain intensity, back disability, lumbar range of motion, and quality of life in LBP patients were included. Pooled effect sizes were calculated using random effects models and 95 % confidence interval (95 % CI). RESULTS: Data from eight RCTs (386 patients with back pain) meeting the inclusion criteria were extracted for meta-analysis with methodological quality assessment scores ranging from 6 to 10. Compared to the control intervention, MFR induced significant decrease in back disability (SMD = -0.35, 95 % confidence interval [CI] = -0.68, -0.02, P = 0.04, I² = 46 %, n = 284). MFR induced non-significant decrease in the pain intensity (SMD = -0.12, 95 % confidence interval[CI] = -0.35, 0.11, P = 0.32, I² = 0%, n = 294), non-significant improvement in quality of life (SMD = -0.09, 95 % confidence interval [CI] = -0.46, 0.28, P = 0.62, I² = 0%, n = 114), and non-significant improvement in lumbar range of motion (Flexion SMD = 0.57,95 % confidence interval [CI] = -0.09, 1.24, P = 0.09, I² = 54 %, n = 80) (Extension SMD = 0.68, 95 % confidence interval[CI] = -0.72, 2.08, P = 0.34, I² = 89 %, n = 80) (Right flexion SMD = 0.05, 95 % confidence interval[CI] = -0.90, 0.99, P = 0.92, I² = 78 %, n = 80) (Left flexion SMD = 0.14, 95 % confidence interval[CI] = -0.59, 0.88, P = 0.70, I² = 64 %, n = 80). CONCLUSION: The findings suggest that MFR can improve the effect of physical therapy alone and exercise therapy alone, and that MFR can be an effective adjuvant therapy. Meta-analysis showed that MFR has a significant effect on reducing back disability in patients with low back pain, but no significant effect on reducing pain intensity, improving quality of life, and improving lumbar range of motion.

Comprehensive analysis of tumor microenvironment and identification of an immune signature to predict the prognosis and immunotherapeutic response in lung squamous cell carcinoma.

BACKGROUND: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC). METHODS: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. The immune signature was further constructed and validated in multiple independent datasets by LASSO Cox regression analysis. Next, the value of immune signature in predicting the response of immunotherapy was evaluated. Finally, the possible mechanism of immune signature was also investigated. RESULTS: A novel immune signature based on 5 genes was constructed and validated to predict the prognosis of LUSC patients. These genes were filamin-C, Rho family GTPase 1, interleukin 4-induced gene-1, transglutaminase 2, and prostaglandin I2 synthase. High-risk patients had significantly poorer survival than low-risk patients. A nomogram was also developed based on the immune signature and tumor stage, which showed good application. Furthermore, we found that the immune signature had a significant correlation with immune checkpoint, microsatellite instability, tumor infiltrating lymphocytes, cytotoxic activity scores, and T-cell-inflamed score, suggesting low-risk patients are more likely to benefit from immunotherapy. Finally, functional enrichment and pathway analyses revealed several significantly enriched immune-related biological processes and metabolic pathways. CONCLUSIONS: In the present study, we developed a novel immune signature that could predict prognosis and immunotherapeutic response in LUSC patients. The results not only help identify LUSC patients with poor survival, but also increase our understanding of the immune microenvironment and immunotherapy in LUSC.

Lighting up metallohelices: from DNA binders to chemotherapy and photodynamic therapy.

The design of novel agents that specifically target DNA and interrupt its normal biological processes is an attractive goal in drug design. Among the promising metallodrugs, metal-directed self-assembled metallohelices with defined three-dimensional stereochemical structures display unique structure-inherent and unprecedented noncovalent targeting abilities towards DNA, resulting in excellent anticancer or antibiotic activities. A newly burgeoning hotspot is focusing on lighting them up by embedding luminescent metal ions as the vertices. The photoactive metallohelices that combine strong interactions toward DNA targets and efficient 1O2 quantum yield may provide new motivation in diagnostic and photodynamic therapy (PDT) areas. This perspective focuses on research progress on metallohelices as DNA binders and chemotherapeutic agents, and highlights recent advances in fabricating luminescent examples for PDT. The relative assembly strategies are also discussed and compared. Finally, perspectives on the future development of the lit-up metallohelices are presented.

A Dual Macrophage Targeting Nanovector for Delivery of Oligodeoxynucleotides To Overcome Cancer-Associated Immunosuppression.

To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the monotargeting delivery system containing either MCMC or HA, resulting in a dramatically enhanced secretion of proinflammatory cytokines and a successful shift to activated macrophages (M1). Besides macrophages, the influence of the delivery system on tumor cells (MCF-7) was also investigated. In MCF-7 cells, the increased expressions of nuclear transcription factor-κB (NF-κB), PIK3R3, and phosphorylated protein kinase B (p-Akt) caused by activated NF-κB and phosphoinositide 3-kinase/Akt signalings were observed. Nevertheless, upregulated Fas as well as Fas ligand (FasL) may induce Fas/FasL-mediated apoptosis, which results in the increased expressions of caspases in tumor cells.

[Protective effect of synthetic salidroside on acute lung injury in rats].

To study the protective effect and mechanism of synthetic salidroside on acute lung injury (ALI) induced by lipopolysaccharide (LPS), male Sprague-Dawley (SD) rats were randomly divided into saline control group, 3 mg/kg LPS model group, different doses of salidroside groups (5, 20 and 80 mg/kg), and 5 mg/kg dexamethasone group. Intratracheal LPS instillation was used to establish the ALI model 0.5 h after intraperitoneal injection of salidroside or dexamethasone, and the rats were sacrificed 6 h later. Lung wet/dry weight ratio (W/D) was calculated. Lung tissue pathology and lung injury score (LIS) were observed and evaluated through hematoxylin and eosin (HE) staining. The centrifugal sediment of bronchoalveolar lavage fluid (BALF) was used to count the polymorphonuclear leukocyte (PMN) number by Wright's staining, and the centrifugal supernatant of BALF was used to determine the contents of protein and inflammatory factors (TNF-α, IL-1ß and IL-6). The contents of myeloperoxidase (MPO) and malondialdehyde (MDA) in lung tissue were determined. Western blot was used to detect the expression levels of phosphorylated and total nuclear factor kappa B (NF-κB)/p65 protein in lung tissue. The results showed that, compared with LPS group, the intervention of synthetic salidroside alleviated the pathological damage in lung tissue, decreased the LIS and lung W/D ratio (P < 0.05), reduced the PMN number, the contents of protein and inflammatory factors in BALF (P < 0.05), reduced the contents of MPO and MDA in lung tissue (P < 0.05), and inhibited the expression of p-NF-κB in lung tissue (P < 0.05). The results suggest that synthetic salidroside has a protective effect on ALI induced by LPS, and its mechanism is related to inhibiting the phosphorylation of NF-κB and reducing the aggregation of PMN in the lung.

Fusion peptide functionalized hybrid nanoparticles for synergistic drug delivery to reverse cancer drug resistance.

A facile self-assembly strategy was developed to decorate polymer/inorganic hybrid nano-sized drug delivery systems with functional peptides. To enhance drug delivery efficacy and overcome tumor drug resistance, a functional fusion peptide containing an RGD sequence for tumor targeting and an R8 sequence for cell penetration was introduced onto the surface of biotinylated carboxymethyl chitosan/CaCO3 (BCMC/CaCO3) hybrid nanoparticles through biotin-avidin interaction to obtain peptide functionalized nanoparticles (PNP). The peptide functionalization results in improved delivery efficiency and effective inhibition for drug resistant tumor cells. Co-delivery of an anti-cancerous drug (doxorubicin hydrochloride, DOX) and a cyclooxygenase-2 inhibitor (celecoxib, CXB) by PNP can further improve the therapeutic efficiency by effectively down-regulating P-gp expression to reduce P-gp mediated drug efflux and increase intracellular drug accumulation.

Tumor Targeting Synergistic Drug Delivery by Self-Assembled Hybrid Nanovesicles to Overcome Drug Resistance.

PURPOSE: To overcome multi-drug resistance (MDR) in tumor chemotherapy, a polymer/inorganic hybrid drug delivery platform with tumor targeting property and enhanced cell uptake efficiency was developed. METHOD: To evaluate the applicability of our delivery platform for the delivery of different drug resistance inhibitors, two kinds of dual-drug pairs (doxorubicin/buthionine sulfoximine and doxorubicin/tariquidar, respectively) were loaded in heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles to realize simultaneous delivery of an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells. RESULTS: Prepared by self-assembly, the drug loaded hybrid nanovesicles with a mean size less than 210 nm and a negative zeta potential exhibit good stability in serum contained aqueous media. The in vitro cytotoxicity evaluation indicates that hybrid nanovesicles with tumor targeting biotin moieties have an enhanced tumor cell inhibitory effect. In addition, dual-drug loaded hybrid nanovesicles exhibit significantly stronger cell growth inhibition as compared with doxorubicin (DOX) mono-drug loaded nanovesicles due to the reduced intracellular glutathione (GSH) content by buthionine sulfoximine (BSO) or the P-glycoprotein (P-gp) inhibition by tariquidar (TQR). CONCLUSIONS: The tumor targeting nanovesicles prepared in this study, which can simultaneously deliver multiple drugs and effectively reverse drug resistance, have promising applications in drug delivery for tumor treatments. The polymer/inorganic hybrid drug delivery platform developed in this study has good applicability for the co-delivery of different anti-tumor drug/drug resistance inhibitor pairs to overcome MDR. Graphical Abstract A polymer/inorganic hybrid drug delivery platform with enhanced cell uptake was developed for tumor targeting synergistic drug delivery. The heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles prepared in this study can deliver an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells simultaneously to overcome drug resistance efficiently.