Relationship between dietary live microbe intake and the prevalence of COPD in adults: a cross-sectional study of NHANES 2013-2018.

OBJECTIVE: To explore the potential association between dietary live microbes and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD). METHODS: In this cross-sectional study, data of 9791 participants aged 20 years or older in this study were collected from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018. Participants in this study were classified into three groups according to the Sanders' dietary live microbe classification system: low, medium, and high dietary live microbe groups. COPD was defined by a combination of self-reported physician diagnoses and standardized medical status questionnaires. Logistic regression and subgroup analysis were used to assess whether dietary live microbes were associated with the risk of COPD. RESULTS: Through full adjustment for confounders, participants in the high dietary live microbe group had a low prevalence of COPD in contrast to those in low dietary live microbe group (OR: 0.614, 95% CI: 0.474-0.795, and p < 0.001), but no significant association with COPD was detected in the medium and the low dietary live microbe groups. This inverse relationship between dietary live microbe intake and COPD prevalence was more inclined to occur in smokers, females, participants aged from 40 to 59 years old and non-obese participants. CONCLUSION: A high dietary live microbe intake was associated with a low prevalence of COPD, and this negative correlation was detected especially in smokers, females, participants aged from 40 to 59 years old and non-obese participants.

Detection of tumor marker CA72-4 with an electrochemical immunosensor based on MnO2 nanosheets and HNM-AuPtPd nanocomposites.

To accurately detect tumor marker carbohydrate antigen 72-4 (CA72-4) of serum samples is of great significance for the early diagnosis of malignant tumors. In the present study, MnO2/hollow nanobox metal-organic framework (HNM)-AuPtPd nanocomposites were prepared via multi-step synthesis and superposition method and a series of characterizations were carried out. A highly sensitive immunosensor Ab/MnO2/HNM-AuPtPd/GCE based on the composite nanomaterial was further prepared and used to detect the tumor marker CA72-4. The constructed immunosensor achieved signal amplification by increasing the electrocatalytic activity to H2O2 by means of the synergistic effect of MnO2 ultra-thin nanosheets (MnO2 UNs) and HNM-AuPtPd. At the same time, the electrochemical properties of the immunosensor were analyzed using cyclic voltammetry, electrochemical impedance, amperometry (with the test voltage of -0.4 V), and differential pulse voltammetry. The experimental results showed that the MnO2/HNM-AuPtPd nanocomposites were successfully prepared, and the immunosensor Ab/MnO2/HNM-AuPtPd/GCE demonstrated an excellent electrochemical performance. The electrochemical immunosensor had the highest detection sensitivity under the optimal experimental conditions, such as incubation pH of 7.0, incubation time of 60 min, with the addition of 15 µL of H2O2, and in the concentration range 0.001-500 U/mL. It had a low detection limit of 1.78×10-5 U/mL (S/N = 3). Moreover, the serum sample recovery were in the range from 99.38 to 100.52%. This study provides a new method and experimental basis for the detection of tumor markers in clinical practice.

Association between carotenoids and the prevalence of chronic obstructive pulmonary disease in the United States.

BACKGROUND: Previous studies mainly concentrated on examining the correlation between single carotenoids and Chronic obstructive pulmonary disease (COPD). However, these findings have been inconsistent. OBJECTIVES: This study aimed to evaluate both the individual and overall associations of carotenoids with the prevalence of COPD. METHODS: This study comprised 2,939 participants chosen from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. The logistic regression, quantile-based G-computation regression (qgcomp), and Bayesian kernel machine regression (BKMR) models were employed to explore the association between carotenoids and the prevalence of COPD. Mediation analyses were also conducted to explore the underlying mechanism of carotenoids on COPD. RESULTS: Individuals diagnosed with COPD had significantly lower serum carotenoid concentrations than those without COPD. We found a negative relationship between combined carotenoids and the prevalence of COPD, and lutein and zeaxanthin and alpha cryptoxanthin were identified as the main contributors to this negative association. Moreover, eosinophil acted as a mediator in the relationship between lutein and zeaxanthin, alpha cryptoxanthin, and the prevalence of COPD, with mediating proportions of 2.75 % and 3.67 %. CONCLUSION: A negative association was observed between combined carotenoids and COPD prevalence, with lutein and zeaxanthin, and alpha cryptoxanthin identified as the main contributors. Eosinophils could potentially mediate the association between carotenoids and COPD.

Exosomes Derived from Mouse Breast Carcinoma Cells Facilitate Diabetic Wound Healing.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS: The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Association of mean RDW values and changes in RDW with in-hospital mortality in ventilator-associated pneumonia (VAP): Evidence from MIMIC-IV database.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a hospital-acquired infection with high mortality, and remains a challenge for clinical treatment. Red blood cell distribution width (RDW) was associated with worse outcomes in several diseases. The purpose of this study was to investigate the relationship between mean RDW values, changes in RDW (delta RDW), and in-hospital mortality among patients with VAP. METHODS: In the present study, we enrolled 1266 VAP patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were categorized into low group, medium group, and high group according to tertiles of mean RDW values. The primary outcome was all-cause in-hospital mortality. Univariate logistic regression analysis, multivariate logistic regression analysis, and restricted cubic spline (RCS) curve were performed to determine the association between mean RDW values and in-hospital mortality in VAP. Moreover, RCS curve was plotted to explore the dose-response relationship between delta RDW and in-hospital mortality in VAP. RESULTS: Among the VAP patients included in the study, the in-hospital mortality was 20.85% with 264 non-survivors and 1002 survivors. The non-survivors exhibited significantly higher mean RDW values and delta RDW values compared to survivors. Multivariate logistic regression analysis indicated that mean RDW values were positively associated with in-hospital mortality in VAP after adjusting for relevant covariates. The RCS curve demonstrated a dose-response relationship between mean RDW and the mortality in VAP. Moreover, a linear relationship was observed between delta RDW and in-hospital mortality in VAP. CONCLUSION: Higher mean RDW values were significantly associated with an increased risk of in-hospital mortality in VAP. Additionally, a linear relationship was found between delta RDW values and in-hospital mortality. These findings suggest that RDW can be used to identify high-risk patients with poorer outcomes in VAP.

A Rapid and Simplified Method to Isolate Specific Regulators Based on Biotin-Avidin Binding Affinities in Crops.

Transcription factors (TFs) are indispensable components of transcriptional regulatory pathways involved in crop growth and development. Herein, we developed a new method for the identification of upstream TFs specific to genes in crops based on the binding affinities of biotin and avidin. First, we constructed and verified the new biotin and avidin system (BAS) by a coprecipitation assay. Subsequently, the feasibility of DNA-based BAS (DBAS) was further proved by in vivo and in vitro assays. Furthermore, we cloned the promoter of rice OsNRT1.1B and the possible regulators were screened and identified. Additionally, partial candidates were validated by the electrophoresis mobility shift assay (EMSA), yeast one-hybrid, and luciferase activity assays. Remarkably, the results showed that the candidates PIP3 and PIP19 both responded to nitrate immediately and overexpression of PIP3 caused retard growth, which indicates that the candidates are functional and the new DBAS method is useful to isolate regulators in crops.

Association between manganese exposure in heavy metals mixtures and the prevalence of sarcopenia in US adults from NHANES 2011-2018.

Environmental pollution is identified as an essential risk factor for sarcopenia. However, the effect of manganese (Mn) exposure on the prevalence of sarcopenia is not assessed. Our study investigated the correlation between blood Mn concentration and sarcopenia risk in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Three statistical methods were used to assess these correlations. Mediation analysis was performed to explore the role of inflammation in Mn exposure-induced sarcopenia. Of the 4957 individuals enrolled in this study, 398 (8 %) were diagnosed with sarcopenia. We found a positive association between the log10 Mn concentration and the prevalence of sarcopenia in the logistic regression model. Moreover, heavy metals mixtures were positively correlated with the prevalence of sarcopenia, with Mn identified as the main contributor to this association in the weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Furthermore, inflammation mediated the relationship between Mn exposure and the prevalence of sarcopenia, explaining 7.29 % of the effect (odds ratio: 0.03, 0.19, P = 0.002). Thus, our study results revealed that excessive Mn exposure is a contributing factor for sarcopenia. More prospective studies are required to examine the association between Mn exposure and the prevalence of sarcopenia.

Association of serum phosphate and changes in serum phosphate with 28-day mortality in septic shock from MIMIC-IV database.

This study aimed to investigate the relationship between serum phosphate levels, changes in serum phosphate levels, and 28-day mortality in patients with septic shock. In this retrospective study, data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients were divided into three groups according to the tertiles of serum phosphate levels. Kaplan-Meier curves and log-rank test analyses were used for survival analysis. Multivariate logistic regression, and restricted cubic spline (RCS) curve were used to explore the association between serum phosphate, delta serum phosphate levels and 28-day mortality. In total, 3296 patients with septic shock were included in the study, and the 28-day mortality was 30.0%. Serum phosphate levels were significantly higher in the non-survivor group than in the survivor group. The Kaplan-Meier curves showed significant differences among the three groups. Multivariate logistic regression analysis and the RCS curve showed that serum phosphate levels were independently and positively associated with the 28-day mortality of septic shock. Non-survivors had higher delta serum phosphate levels than survivors. Survival analysis showed that patients with higher delta serum phosphate levels had higher 28-day mortality. A non-linear relationship was detected between delta serum phosphate and 28-day mortality with a point of inflection at - 0.3 mg/dL. Serum phosphate levels were positively and independently associated with 28-day mortality in septic shock. Delta serum phosphate level was a high-risk factor for patients with septic shock.

Association between serum phosphate and in-hospital mortality of patients with AECOPD: A retrospective analysis on eICU database.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important adverse event in the development of chronic obstructive pulmonary disease (COPD). Hyperphosphatemia is associated with higher mortality in patients with multiple diseases. In this study, we aimed to determine the relationship between serum phosphate and the risk of in-hospital mortality in patients with AECOPD. Methods: In the present study, patients with AECOPD were enrolled in the electronic Intensive Care Unit Collaborative Research Database (eICU-CRD), and divided into three groups according to the tertiles of serum phosphate level. The primary outcome measure was all-cause in-hospital mortality. The association between serum phosphate level and in-hospital mortality was investigated using multivariate logistic regression analysis. Moreover, subgroup analysis was performed to explore whether the relationship was consistent among different subgroups. Results: A total of 1199 AECOPD patients were included in this study. Non-survivors had higher serum phosphate levels than survivors. All patients were classified into lowest tertile, median tertile, and highest tertile, respectively. Multivariate logistic regression analysis indicated that serum phosphate was positively associated with in-hospital mortality after adjusting for confounders. Moreover, there was a significant trend across tertiles when serum phosphate level was diverted as a categorical variable. In addition, subgroup analysis demonstrated that serum phosphate was consistently associated with a higher risk of in-hospital mortality in different subgroups. Conclusion: Higher serum phosphate was positively associated with the increased in-hospital mortality in patients with AECOPD. Hyperphosphatemia may be an underlying high-risk factor for in-hospital mortality owing to AECOPD.

Synergistic wound repair effects of a composite hydrogel for delivering tumor-derived vesicles and S-nitrosoglutathione.

Treating chronic wounds requires transition from proinflammatory M1 to anti-inflammatory M2 dominant macrophages. Based on the role of tumor extracellular vesicles (tEVs) in regulating the phenotypic switching from M1 to M2 macrophages, we propose that tEVs may have a beneficial impact on alleviating the overactive inflammatory microenvironment associated with refractory wounds. On the other hand, as a nitric oxide donor, S-nitrosoglutathione (GSNO) can regulate inflammation, promote angiogenesis, enhance matrix deposition, and facilitate wound healing. In this study, a guar gum-based hydrogel with tEVs and GSNO was designed for the treatment of diabetic refractory wounds. This hybrid hydrogel was formed through the phenyl borate bonds, which can automatically disintegrate in response to the high reactive oxygen species (ROS) level at the site of refractory diabetic wounds, releasing tEVs and GSNO. We conducted a comprehensive evaluation of this hydrogel in vitro, which demonstrated excellent performance. Meanwhile, using a full-thickness excision model in diabetic mice, the wounds exposed to the therapeutic hydrogel healed completely within 21 days. The increased closure rate was associated with macrophage polarization and collagen deposition, accelerated fibroblast proliferation, and increased angiogenesis in the regenerating tissues. Therefore, this multifunctional hybrid hydrogel appears to be promising for clinical applications.

Genome-wide identification of nitrate-responsive microRNAs by small RNA sequencing in the rice restorer cultivar Nanhui 511.

Rice productivity relies heavily on nitrogen fertilization, and improving nitrogen use efficiency (NUE) is important for hybrid rice breeding. Reducing nitrogen inputs is the key to achieving sustainable rice production and reducing environmental problems. Here, we analyzed the genome-wide transcriptomic changes in microRNAs (miRNAs) in the indica rice restorer cultivar Nanhui 511 (NH511) under high (HN) and low nitrogen (LN) conditions. The results showed that NH511 is sensitive to nitrogen supplies and HN conditions promoted the growth its lateral roots at the seedling stage. Furthermore, we identified 483 known miRNAs and 128 novel miRNAs by small RNA sequencing in response to nitrogen in NH511. We also detected 100 differentially expressed genes (DEGs), including 75 upregulated and 25 downregulated DEGs, under HN conditions. Among these DEGs, 43 miRNAs that exhibited a 2-fold change in their expression were identified in response to HN conditions, including 28 upregulated and 15 downregulated genes. Additionally, some differentially expressed miRNAs were further validated by qPCR analysis, which showed that miR443, miR1861b, and miR166k-3p were upregulated, whereas miR395v and miR444b.1 were downregulated under HN conditions. Moreover, the degradomes of possible target genes for miR166k-3p and miR444b.1 and expression variations were analyzed by qPCR at different time points under HN conditions. Our findings revealed comprehensive expression profiles of miRNAs responsive to HN treatments in an indica rice restorer cultivar, which advances our understanding of the regulation of nitrogen signaling mediated by miRNAs and provides novel data for high-NUE hybrid rice cultivation.

Transcriptomic and Physiological Analyses of Two Rice Restorer Lines under Different Nitrogen Supplies Provide Novel Insights into Hybrid Rice Breeding.

Improving plant nitrogen-use efficiency (NUE) has great significance for various crops, particularly in hybrid breeding. Reducing nitrogen inputs is key to achieving sustainable rice production and mitigating environmental problems. In this study, we analyzed the transcriptomic and physiological changes in two indica restorer lines (Nanhui511 [NH511] and Minghui23 [MH23]) under high nitrogen (HN) and low nitrogen (LN) conditions. Compared to MH23, NH511 was more sensitive to different nitrogen supplies and exhibited higher nitrogen uptake and NUE under HN conditions by increasing lateral root and tiller numbers in the seedling and maturation stages, respectively. NH511 also exhibited a lower survival rate than MH23 when planted in a chlorate-containing hydroponic solution, indicating its HN uptake ability under different nitrogen-supply conditions. Transcriptomic analysis showed that NH511 has 2456 differentially expressed genes, whereas MH23 had only 266. Furthermore, these genes related to nitrogen utilization showed differential expression in NH511 under HN conditions, while the opposite was observed in MH23. Our findings revealed that NH511 could be regarded as elite rice and used for breeding high-NUE restorer lines by regulating and integrating nitrogen-utilization genes, which provides novel insights for the cultivation of high-NUE hybrid rice.

Association between ethylene oxide exposure and prevalence of COPD: Evidence from NHANES 2013-2016.

BACKGROUND: Environmental exposures are major risk factors for chronic obstructive pulmonary disease (COPD). Ethylene oxide (EO) is a ubiquitous organic compound and adversely affects human health. However, it remains unknown whether EO exposure increases the risk of COPD. This study aimed to explore the association between EO exposure and the prevalence of COPD. METHODS: In this cross-sectional study, 2243 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016. Participants were classified into four groups according to quartiles of log10-transformed hemoglobin adducts of EO (HbEO) levels. HbEO levels were measured using the modified Edman reaction and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Logistic regression, restricted cubic spline regression model, and subgroup analysis were used to assess whether EO exposure was associated with the risk of COPD. A multivariate linear regression model was used to investigate the correlation between HbEO levels and inflammatory factors. A mediating analysis was conducted to estimate whether inflammatory factors were involved in the effects of HbEO on the prevalence of COPD. RESULTS: Participants with COPD had higher HbEO levels than those without COPD. Log10-transformed HbEO levels were associated with an increased risk of COPD after adjusting for all covariates. [Q4 vs. Q1 in model II: OR = 2.15, 95 % CI: 1.20-3.85, P = 0.010, P for trend = 0.009]. Moreover, a nonlinear J-shaped relationship was observed between HbEO levels and the risk of COPD. Furthermore, HbEO levels were positively correlated with inflammatory cells. In addition, white blood cells and neutrophils mediated the relationship between HbEO and the prevalence of COPD with mediated proportions of 10.37 % and 7.55 %, respectively. CONCLUSION: These findings indicate that EO exposure has a J-shaped association with the risk of COPD. Inflammation is a key mediator involved in the effects of EO exposure on COPD.

An AIEgen-based "turn-on" probe for sensing cancer cells and tiny tumors with high furin expression.

Peptide-aggregation-induced emission (AIE) luminogen (AIEgen) conjugates are widely used in the bioimaging field for their good resistance to photobleaching, red and near-infrared light emission, good biocompatibility, etc. However, their peptides are mainly negatively charged and the positively charged peptide-AIEgen conjugates are rarely used in in vivo imaging due to their high non-specific interaction with protein to cause "false-positive" results and their potential risk of triggering hemolysis. Herein, we introduce a black hole quencher 3 (BHQ3) to RVRRGFF-AIE (FA) to build a "turn-on" probe, named BHQ3-RVRRGFF-AIE (BFA). Compared with FA, BFA has advantages in the anti-interference ability for different proteins and many solution environments. But, both BFA and FA have high risks of inducing hemolysis, which restricts their further application. Through co-assembly with poly-γ-glutamic acid (γ-PGA), molecular probes BFA and FA are formed into PGA-BFA and PGA-FA nanoparticles with high biocompatibility and suppressed phototoxicity. Cell studies show that PGA-BFA can discriminate cancer cells with high furin expression from low furin-expressed cancer cells and normal cells. In vivo studies show that PGA-BFA can light up tiny tumors in the abdominal cavity with a better tumor-to-intestine ratio (3.14) than that of PGA-FA (1.47), which is helpful for the accurate excision of tiny tumors. This study will advance the development of constructing good biosafety probes with a high signal-to-noise ratio for fluorescence image-guided cancer surgery.

Menstrual blood-derived endometrial stem cells inhibit neuroinflammation by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 pathway.

Neuroinflammation is a common response in various neurological disorders. Mesenchymal stem cell-based treatment has become a promising therapy for neuroinflammation-associated diseases. However, the effects of mesenchymal stem cells are controversial, and the underlying mechanism is incompletely understood. In the present study, menstrual blood-derived endometrial stem cells were intravenously transplanted into a mouse model of neuroinflammation established by peripheral injection of lipopolysaccharide. Microglial cells challenged with lipopolysaccharide were cultured with conditioned medium from endometrial stem cells. The levels of cytokines were detected by enzyme-linked immunosorbent assay. Cell proliferation and death were detected by Cell Counting Kit 8 and flow cytometry, respectively. The expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), NLR family pyrin domain containing 3 (NLRP3) and caspase 1 (Casp1) were evaluated by western blotting. The results showed that intravenous transplantation of endometrial stem cells downregulated proinflammatory factors and upregulated anti-inflammatory factors in the brain of mice with neuroinflammation. Conditioned medium suppressed the inflammatory reaction and hyperactivation of microglial cells and protected microglial cells from cell death induced by lipopolysaccharide in vitro. The expression of TLR4, MyD88, NLRP3 and Casp1 in the brain of mice with neuroinflammation and in lipopolysaccharide-stimulated microglial cells was downregulated by endometrial stem cells and conditioned medium, respectively. These data suggested that menstrual blood-derived endometrial stem cells may suppress neuroinflammatory reactions partially by regulating microglia through the TLR4/MyD88/NLRP3/Casp1 signalling pathway. Our findings may be very useful for the development of an alternative stem cell-based therapy for neuroinflammation-associated disorders.

Facile fabrication of a biodegradable multi-hollow iron phosphate nanoplatform for tumor-specific nanocatalytic therapy and chemotherapy.

In this study, a type of biodegradable multi-hollow iron phosphate (FeP) with excellent Fenton reaction ability and doxorubicin (DOX) loading capacity is synthesized in one-pot. This hollow FeP with complex interior not only affords high drug loading efficiency, but also obviates DOX leakage in normal tissues. In order to inhibit the formation of inert Fe(OH)x and endow the nanoplatform with a highly hydrophilic surface, PEG was anchored to it with a dopamine linkage, which formed an Fe chelating complex. DOX-loaded FeP modified with PEG could be disintegrated when responding to the lysosomal acid environment, releasing both ferric and ferrous ions as well as DOX. Therefore, apart from chemotherapy with DOX, the continuously generated iron ions catalyze a fast Fenton reaction with the innate H2O2 in tumor cells and produce abundant highly toxic hydroxyl radicals for nanocatalytic tumor therapy. Taken together, we believe that this nanoplatform will significantly advance the fields of both Fe-based nanomaterials and nanocatalytic tumor therapy.

Direct Modification of Extracellular Vesicles and Its Applications for Cancer Therapy: A Mini-Review.

Extracellular vesicles (EVs) are a class of lipid membrane-bound vesicles released by various cells and mediate cell-to-cell communication. By reason of their high physiochemical stability and biocompatibility, EVs are considered as novel drug delivery system. An increasing number of studies have indicated that EVs can be modified to enhance their loading efficiency, targeting ability and therapeutic capabilities for cancer therapy. Compared with the tedious process of gene engineering approaches, direct modification of EVs is easier, faster and versatile. This mini review will summarize the prevailing approaches for direct modification of EVs. Additionally, the potential applications of modified EVs in cancer therapy are also discussed, which will help readers gain a better understanding of the technologies and applications in this field.

A heparin-functionalized covered stent prepared by plasma technology.

In this study, the surface of the covered stent was treated by plasma technology to introduce amino functional groups, and glutaraldehyde and heparin were successfully grafted to prepare a heparin-functionalized covered stent (HPLCS). The preparation parameters such as plasma treatment power, plasma treatment time, concentration of glutaraldehyde and heparin, and pH of heparin solution were studied in detail. The functionalized heparin covered stent can make the titer of heparin reach 1.23 ± 0.03 IU/cm2. In animal experiments, after implantation in pigs for 6 months, the titer of heparin can still reach 0.93 ± 0.05 IU/cm2. This work provides a good method for preparing heparin covered stent.

Two Cholesterol Recognition Amino Acid Consensus Motifs of GP64 with Uncleaved Signal Peptide Are Required for Bombyx mori Nucleopolyhedrovirus Infection.

The signal peptide (SP) of integrated membrane proteins is removed cotranslationally or posttranslationally in the endoplasmic reticulum, while GP64, a membrane fusion protein of Bombyx mori nucleopolyhedrovirus (BmNPV), retains its SP in the mature protein and virion. In this study, we revealed that uncleaved SP is a key determinant with additional functions in infection. First, uncleaved SP endows BmNPV with strong virulence; second, SP retention-induced BmNPV infection depends on cholesterol recognition amino acid consensus domain 1 (CRAC1) and CRAC2. In contrast, the recombinant virus with SP-cleaved GP64 has reduced infectivity, and only CRAC2 is required for BmNPV infection. Furthermore, we showed that cholesterol in the plasma membrane is an important fusion receptor that interacts with CRAC2 of GP64. Our study suggested that BmNPV GP64 is a key cholesterol-binding protein and uncleaved SP determines GP64's unique dependence on the CRAC domains. IMPORTANCE BmNPV is a severe pathogen that mainly infects silkworms. GP64 is the key membrane fusion protein that mediates BmNPV infection, and some studies have indicated that cholesterol and lipids are involved in BmNPV infection. A remarkable difference from other membrane fusion proteins is that BmNPV GP64 retains its SP in the mature protein, but the cause is still unclear. In this study, we investigated the reason why BmNPV retains this SP, and its effects on protein targeting, virulence, and CRAC dependence were revealed by comparison of recombinant viruses harboring SP-cleaved or uncleaved GP64. Our study provides a basis for understanding the dependence of BmNPV infection on cholesterol/lipids and host specificity.

Pressure-driven accumulation of Mn-doped mesoporous silica nanoparticles containing 5-aza-2-deoxycytidine and docetaxel at tumours with a dry cupping device.

Drug delivery with the help of nanoparticles could transport more payloads to tumour site. Owing to their limited accumulation and penetration in the tumour tissues, to increase delivery efficiency is currently still required for applying nanomedicine to treat tumour. Here, we initially report a pressure-driven accumulation of drug-loaded nanoparticles to tumours for efficient tumour therapy with a dry cupping device. The mesoporous Mn-doped silica based nanoparticles delivering 5-aza-2-deoxycytidine and docetaxel were prepared, characterised and used as a model nanomedicine to investigate the potential of dry cupping treatment. For this system, the Mn doping not only endowed the mesoporous silica nanoparticles biodegradability, but also made it much easier to bind a tumour targeting group, which is a G-quadruplex-forming aptamer AS1411. On tumour-bearing mice, the in vivo results demonstrated that the dry cupping treatment could substantially improve the distribution of nanomedicines at tumour site, resulting in enhanced treatment efficacy. Overall, this method enables the therapeutical nanoparticles accumulate to tumour through increasing the blood perfusion as well as altering the biological barrier, which opened up possibilities for the development of pressure-driven nanomedicine accumulation at tumour site.