AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were rand...AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by realtime polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean bodymass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-na■ve patients with chronic HCV genotype 1 infection significantly improves the viral response.展开更多
Background Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-β1 （TGF-β1） to cartilage defects can enhance chondrogenesis. In this stu...Background Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-β1 （TGF-β1） to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-β1 delivery and the effect of released TGF-β1 on the chondrogenic potential of chondrocytes. Methods Chitosan scaffolds and chitosan microspheres loaded with TGF-β1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-β1 microspheres and incubated in vitro for 3 weeks. Histological examination and type Ⅱ collagen immunohistochemical staining was performed to evaluate the effects of released TGF-β1 on cell adhesivity, proliferation and synthesis of the extracellular matrix. Results TGF-β1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF-β1 was high （90.1%）. During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-β1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-β1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group （32.7%± 10.4%） was significantly lower than that in the controlled TGF-β1 release group （92.4%±4.8%, 展开更多
Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen t...Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus （HCV） infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine （SOC-3）; both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients＇. ＂viral＂ and ＂metabolic＂ insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include： （1） steatosis, （2） hyperleptinemia, （3） increased TNF production, （4） impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice （60%） in patients with HOMA ≤ 2 than patients with HOMA 〉 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin （at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state） was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.展开更多
Diabetes mellitus,with sustained high-sugar levels in the blood,has been steadily rising in prevalence worldwide.Around 12–14%of the US population has been diagnosed with diabetes in recent years.1 One major reason f...Diabetes mellitus,with sustained high-sugar levels in the blood,has been steadily rising in prevalence worldwide.Around 12–14%of the US population has been diagnosed with diabetes in recent years.1 One major reason for the rise of diabetes is dietary changes.Increased consumption of processed carbohydrates with inadequate consumption of dietary fiber(DF)has been recognized as a major risk factor for diabetes,as hypothesized several decades ago by Trowell.展开更多
Microneedles have attracted increasing interest among various medical fields due to their painless,noninvasive,and efficient way of drug delivery.However,practical applications of these microneedles in different epide...Microneedles have attracted increasing interest among various medical fields due to their painless,noninvasive,and efficient way of drug delivery.However,practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity.Here,inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles,we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities.With polydopamine hydrogel as the microneedle base and a loop of suctioncup-structured concave chambers encircling each microneedle,the generated microneedles can fit the skin well;keep strong adhesion in dry,moist,and wet environments;and realize self-repair after being split into two parts.Besides,as polymyxin is loaded into both the hydrogel tips and the polydopamine base,the microneedles are endowed with excellent ability to resist common bacteria during storage and usage.We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model.These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.展开更多
Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the ...Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as “hepatitis C-associated dysmetabolic syndrome” (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.展开更多
AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still...AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.展开更多
Sustained casing pressure （SCP） in gas wells brings a serious threat to worker safety and environmental protection. According to geological conditions, wellbore structure and cement data of gas wells in the Sichuan-...Sustained casing pressure （SCP） in gas wells brings a serious threat to worker safety and environmental protection. According to geological conditions, wellbore structure and cement data of gas wells in the Sichuan-Chongqing region, China, the position, time, environmental condition and the value of SCP have been analyzed. On this basis, the shape of the pressure bleed-down plot and pressure buildup plot were diagnosed and the mechanism of SCP has been clarified. Based on generalized annular Darcy percolation theory and gas-liquid two-phase fluid dynamics theory, a coupled mathematical model of gas migration in a cemented annulus with a mud column above the cement has been developed. The volume of gas migrated in the annulus and the value of SCP changing with time in a gas well in Sichuan have been calculated by this model. Calculation results coincided well with the actual field data, which provide some reference for the following security evaluation and solution measures of SCP.展开更多
Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunom...Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.展开更多
Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable ...Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patient展开更多
Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery o...Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.展开更多
AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation param...AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.展开更多
By using the twice-daily atmospheric observation data from 1998 to 2012,station rainfall data,Tropical Rainfall Measure Mission（TRMM） data,as well as the plateau vortex and shear line year book,characteristics of th...By using the twice-daily atmospheric observation data from 1998 to 2012,station rainfall data,Tropical Rainfall Measure Mission（TRMM） data,as well as the plateau vortex and shear line year book,characteristics of the sustained departure plateau vortexes（SDPVs） are analyzed.Some new useful observational facts and understanding are obtained about the SDPV activities.The following results are obtained.（1）The active period of SDPVs is from June to August,most in July,unlike that of the unsustained departure plateau vortexes（UDPVs）,which have same occurrence frequencies in the three summer months.（2）The SDPVs,generated mainly in the Qumalai neighborhood and situated in a sheared surrounding,move eastward or northeastward,while the UDPVs are mainly led by the upper-level trough,and move eastward or southeastward.（3） The SDPVs influence wide areas of China,even far to the Korean Peninsula,Japan,and Vietnam.（4） The SDPVs change their intensities and properties on the way to the east.Most of them become stronger and produce downpour or sustained regional rainstorms to the south of Yellow River.（5）The longer the SDPV sustains,the more baroclinity it has.（6） When an SDPV moves into the sea,its central pressure descends and rainfall increases in all probability.（7） An SDPV might spin over the bend of the Yellow River when there exists a tropical cyclone in the East China Sea.It could also move oppositely to a landed tropical low pressure originated from the sea to the east of Taiwan or from the South China Sea.展开更多
BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved...BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or 展开更多
Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.I...Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.展开更多
Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,...Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,which is known as cytokine storm syndrome.1-3 Elaborating the anti-inflammatory response is crucial to these patients,and interieukin-6(IL6)inhibitors and steroids have been recommended in clinical practice.1 However,after the cytokine storm phase,the host immune response to sepsis may develop into a protracted immunosuppressive phase.展开更多
Silver nanoparticles (Ag NPs) can effectively address the issue of antibiotic-resistant bacterial infections to reduce the potential toxicity of Ag NPs. Although challenging, it is, therefore, necessary to achieve the...Silver nanoparticles (Ag NPs) can effectively address the issue of antibiotic-resistant bacterial infections to reduce the potential toxicity of Ag NPs. Although challenging, it is, therefore, necessary to achieve the sustainable release of Ag+ ions from a finite amount of Ag NPs. This study aims at designing an efficient and benign antimicrobial silver-based ternary composite composed of photocatalysis zinc oxide (ZnO) and reduced graphene oxide (rGO) as a carrier, in which the reactive oxygen species (ROS) excited from ZnO and Ag+ ions released from the Ag NPs cooperate to realize an effective antibacterial activity against E. coli and S. aureus. The constant effective bacterial performance of the ternary photocatalyst with minimum Ag content can be attributed to the increase in the available quantity of ROS, which results from the enhanced separation efficiency of the photogenerated carriers. The proposed system notably realized the long-term sustainable release of Ag+ ions with low concentration for 30 days when compared with an equivalent amount of silver nitrate. Moreover, the use of the composite prevents biotoxicity and silver wastage, and imparts enhanced stability to the long-lasting antibacterial efficacy.展开更多
文摘AIM: To determine whether adding vitamin D, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHODS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin D3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin D. HCV-RNA was assessed by realtime polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean bodymass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P < 0.01), viral load (50% vs 42%, P < 0.01), and fibrosis score (> F2: 42% vs 19%, P < 0.001) than the controls. At week 4, 16 (44%) treated patients and 6 (17%) controls were HCV-RNA negative (P < 0.001). At week 12, 34 (94%) treated patients and 17 (48%) controls were HCV-RNA negative (P < 0.001). At 24 wk post-treatment (SVR), 31 (86%) treated patients and 15 (42%) controls were HCV-RNA negative (P < 0.001). Viral load, advanced fibrosis and vitamin D supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin D to conventional Peg-α-2b/ribavirin therapy for treatment-na■ve patients with chronic HCV genotype 1 infection significantly improves the viral response.
基金the National Natural Science Foundation of China (No. 30000056)the Science and Technology Project Foundation of Guangdong Province (No.2003A302102).
文摘Background Natural articular cartilage has a limited capacity for spontaneous regeneration. Controlled release of transforming growth factor-β1 （TGF-β1） to cartilage defects can enhance chondrogenesis. In this study, we assessed the feasibility of using biodegradable chitosan microspheres as carriers for controlled TGF-β1 delivery and the effect of released TGF-β1 on the chondrogenic potential of chondrocytes. Methods Chitosan scaffolds and chitosan microspheres loaded with TGF-β1 were prepared by the freeze-drying and the emulsion-crosslinking method respectively. In vitro drug release kinetics, as measured by enzyme-linked immunosorbent assay, was monitored for 7 days. Lysozyme degradation was performed for 4 weeks to detect in vitro degradability of the scaffolds and the microspheres. Rabbit chondrocytes were seeded on the scaffolds containing TGF-β1 microspheres and incubated in vitro for 3 weeks. Histological examination and type Ⅱ collagen immunohistochemical staining was performed to evaluate the effects of released TGF-β1 on cell adhesivity, proliferation and synthesis of the extracellular matrix. Results TGF-β1 was encapsulated into chitosan microspheres and the encapsulation efficiency of TGF-β1 was high （90.1%）. During 4 weeks of incubation in lysozyme solution for in vitro degradation, the mass of both the scaffolds and the microspheres decreased continuously and significant morphological changes was noticed. From the release experiments, it was found that TGF-β1 could be released from the microspheres in a multiphasic fashion including an initial burst phase, a slow linear release phase and a plateau phase. The release amount of TGF-β1 was 37.4%, 50.7%, 61.3%, and 63.5% for 1, 3, 5, and 7 days respectively. At 21 days after cultivation, type II collagen immunohistochemical staining was performed. The mean percentage of positive cells for collagen type II in control group （32.7%± 10.4%） was significantly lower than that in the controlled TGF-β1 release group （92.4%±4.8%,
基金Supported by a grant of PAI-CTS-532 from Junta de Andalucía, Andalucía, Spain
文摘Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus （HCV） infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine （SOC-3）; both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients＇. ＂viral＂ and ＂metabolic＂ insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include： （1） steatosis, （2） hyperleptinemia, （3） increased TNF production, （4） impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice （60%） in patients with HOMA ≤ 2 than patients with HOMA 〉 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin （at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state） was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.
基金This study was supported partly from NIH grants(R01AI074745,R01DK076616,R01AI080769 and R01AI121302).
文摘Diabetes mellitus,with sustained high-sugar levels in the blood,has been steadily rising in prevalence worldwide.Around 12–14%of the US population has been diagnosed with diabetes in recent years.1 One major reason for the rise of diabetes is dietary changes.Increased consumption of processed carbohydrates with inadequate consumption of dietary fiber(DF)has been recognized as a major risk factor for diabetes,as hypothesized several decades ago by Trowell.
基金This work was supported by the National Natural Science Foundation of China(grants 61927805 and 51522302)the Natural Science Foundation of Jiangsu(Grant no.BE2018707)the Scientific Research Foundation of Nanjing University and Drum Tower Hospital.
文摘Microneedles have attracted increasing interest among various medical fields due to their painless,noninvasive,and efficient way of drug delivery.However,practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity.Here,inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles,we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities.With polydopamine hydrogel as the microneedle base and a loop of suctioncup-structured concave chambers encircling each microneedle,the generated microneedles can fit the skin well;keep strong adhesion in dry,moist,and wet environments;and realize self-repair after being split into two parts.Besides,as polymyxin is loaded into both the hydrogel tips and the polydopamine base,the microneedles are endowed with excellent ability to resist common bacteria during storage and usage.We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model.These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.
文摘Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host’s metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as “hepatitis C-associated dysmetabolic syndrome” (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.
文摘AIM: To elucidate risk factors contributing to the development of hepatocellular carcinoma (HCC) among patients with sustained viral response (SVR) after interferon (IFN) treatment and to examine whether HCV-RNA still remained in the liver of SVR patients who developed HCC. METHODS: Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this study. We retrospectively reviewed clinical, viral and histological features of the patients, and examined whether the development of HCC depends on several clinical variables using Kaplan-Meier Method. RT-PCR was used to seek HCV-RNA in 3 out of 7 patients in whom liver tissue was available for molecular analysis. RESULTS: Among the enrolled 266 patients with SVR, HCC developed in 7 patients (7/266; 2.6%). We failed to detect HCV-RNA both in cancer and non-cancerous liver tissue in all three patients. The cumulative incidence for HCC was significantly different depending on hepatic fibrosis (F3-4) (P = 0.0028), hepatic steatosis (Grade 2-3) (P = 0.0002) and age (≥ 55) (P = 0.021) at the pre-interferon treatment. CONCLUSION: The current study demonstrated that age, hepatic fibrosis, and hepatic steatosis at pre- interferon treatment might be risk factors for developing HCC after SVR.
基金co-financed by the China National Natural Science Foundation and Shanghai Baosteel Group Corporation (No. 51074135)Program for New Century Excellent Talents in University (No. NCET-08-0907)Jilin Oilfield Company Project (No. JS10-W-14-JZ-32-51)
文摘Sustained casing pressure （SCP） in gas wells brings a serious threat to worker safety and environmental protection. According to geological conditions, wellbore structure and cement data of gas wells in the Sichuan-Chongqing region, China, the position, time, environmental condition and the value of SCP have been analyzed. On this basis, the shape of the pressure bleed-down plot and pressure buildup plot were diagnosed and the mechanism of SCP has been clarified. Based on generalized annular Darcy percolation theory and gas-liquid two-phase fluid dynamics theory, a coupled mathematical model of gas migration in a cemented annulus with a mud column above the cement has been developed. The volume of gas migrated in the annulus and the value of SCP changing with time in a gas well in Sichuan have been calculated by this model. Calculation results coincided well with the actual field data, which provide some reference for the following security evaluation and solution measures of SCP.
文摘Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.
基金Ascletis Pharmaceuticals Co.,Ltd.provided financial support for this study(MANASA)
文摘Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patient
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 81773826)the Double First-Class(CPU2018PZQ13,China)of the China Pharmeutical University+2 种基金the Ministry of Science and Technology of China(2018ZX09711001)the Shanghai Science and Technology Committee(19430741500,China)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of traditional Chinese Medicine(TCM201905,China)
文摘Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
文摘AIM To determine steatosis and fibrosis prevalence in hepatitis C patients after a sustained virological response achieved with direct-acting antivirals.METHODS Transient elastography with controlled attenuation parameter(CAP) was used to assess hepatic steatosis post-sustained virological response(SVR);the CAP technology was not available in the United States at study initiation.Liver stiffness/fibrosis was measured before and 47 wk after treatment completion.Patients with genotype 3 and patients with cirrhosis were excluded.RESULTS One hundred and one patients were included in the study.Post-SVR there were decreases from baseline in alanine aminotransferase(ALT)(63.1 to 17.8 U/L),aspartate aminotransferase(51.8 to 21.5 U/L) and fibrosis score(7.4 to 6.1 k Pa)(P < 0.05).Post-SVR,48 patients(47.5%) had steatosis on CAP;of these,6.25% had advanced fibrosis.Patients with steatosis had higher body mass index(29.0 vs 26.1 kg/m2),glucose(107.8 vs 96.6 mg/d L),ALT(20.4 vs 15.3 mg/d L),CAP score(296.3 vs 212.4 d B/m) and fibrosis score(7.0 vs 5.3 k Pa);P < 0.05.Interestingly,compared to baseline,both patients with and without steatosis had change in fibrosis score post-SVR(7.7 k Pa vs 7.0 k Pa and 7.0 k Pa vs 5.3 k Pa);alternatively,(P < 0.05) and therefore patients with steatosis continued to have clinically significant stiffness(≥ 7 k Pa).CONCLUSION Fatty liver is very common in hepatitis C virus(HCV) patients post-SVR.These patients continue to have elevated mean fibrosis score(≥ 7 k Pa) compared to those without fatty liver;some have advanced fibrosis.Long term follow up is needed to assess steatosis and fibrosis in HCV patients post-SVR.
基金Supported by the National Natural Science Foundation of China(41275052)National(Key)Basic Research and Development(973)Program of China(2012CB417202)
文摘By using the twice-daily atmospheric observation data from 1998 to 2012,station rainfall data,Tropical Rainfall Measure Mission（TRMM） data,as well as the plateau vortex and shear line year book,characteristics of the sustained departure plateau vortexes（SDPVs） are analyzed.Some new useful observational facts and understanding are obtained about the SDPV activities.The following results are obtained.（1）The active period of SDPVs is from June to August,most in July,unlike that of the unsustained departure plateau vortexes（UDPVs）,which have same occurrence frequencies in the three summer months.（2）The SDPVs,generated mainly in the Qumalai neighborhood and situated in a sheared surrounding,move eastward or northeastward,while the UDPVs are mainly led by the upper-level trough,and move eastward or southeastward.（3） The SDPVs influence wide areas of China,even far to the Korean Peninsula,Japan,and Vietnam.（4） The SDPVs change their intensities and properties on the way to the east.Most of them become stronger and produce downpour or sustained regional rainstorms to the south of Yellow River.（5）The longer the SDPV sustains,the more baroclinity it has.（6） When an SDPV moves into the sea,its central pressure descends and rainfall increases in all probability.（7） An SDPV might spin over the bend of the Yellow River when there exists a tropical cyclone in the East China Sea.It could also move oppositely to a landed tropical low pressure originated from the sea to the east of Taiwan or from the South China Sea.
文摘BACKGROUND Direct-acting antiviral agents(DAAs)are extremely effective in eradicating hepatitis C virus(HCV)in chronically infected patients.However,the protective role of the sustained virologic response(SVR)achieved by second-and thirdgeneration DAAs against the onset of hepatocellular carcinoma(HCC)and mortality is less well established.AIM To examine the occurrence of HCC or death from any cause in a retrospectiveprospective study of patients treated with DAAs.METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy.The study was conducted in 380 patients(age:60±13 years,224 males,32%with cirrhosis)treated with DAAs with or without SVR(95/5%),with a median follow up of 58 wk(interquartile range:38-117).The baseline anthropometric features,HCV viral load,severity of liver disease,presence of extra-hepatic complications,coinfection with HIV and/or HBV,alcohol consumption,previous interferon use,alphafetoprotein levels,and renal function were considered to be confounders.RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years,respectively(incidence rate ratio:44,95%CI:15-136,P<0.001).Considering the combined endpoint of HCC or death from any cause,the hazard ratio(HR)for the SVR patients was 0.070(95%CI:0.025-0.194,P<0.001).Other independent predictors of HCC or death were low HCV viremia(HR:0.808,P=0.030),low platelet count(HR:0.910,P=0.041),and presence of mixed cryoglobulinemia(HR:3.460,P=0.044).Considering SVR in a multi-state model,the independent predictors of SVR achievement were absence of cirrhosis(HR:0.521,P<0.001)and high platelet count(HR:1.019,P=0.026).Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR(HR:5.982,P=0.028 and HR:5.633,P=0.047,respectively).CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death.A residual risk of HCC persists in patients with advanced liver disease or
基金The financial support from the National Natural Science Foundation of China(No.51403202,51622307,51390484,51520105004)are gratefully thanked.
文摘Melanoma has been a serious threat to the human health;however,effective therapeutic methods of this cancer are still limited.Combined local therapy is a crucial approach for achieving a superior anti-tumor efficacy.In this paper,a chemo-immunotherapy system of DOX,IL-2 and IFN-g based on poly(g-ethyl-Lglutamate)-poly(ethylene glycol)-poly(g-ethyl-L-glutamate)(PELG-PEG-PELG)hydrogel was developed for local treatment of melanoma xenograft.The drug release process of this system exhibited a short term of burst release(the first 3 days),followed by a long-term sustained release(the following 26 days).The hydrogel degraded completely within 3 weeks without obvious inflammatory responses in the subcutaneous layer of rats,showing a good biodegradability and biocompatibility.The DOX/IL-2/IFN-g co-loaded hydrogel also showed enhanced anti-tumor effect against B16F10 cells in vitro,through increasing the ratio of cell apoptosis and G2/S phage cycle arrest.Moreover,the combined strategy presented improved therapy efficacy against B16F10 melanoma xenograft without obvious systemic side effects in a nude mice model,which was likely related to both the enhanced tumor cell apoptosis and the increased proliferation of the CD3t/CD4t T-lymphocytes and CD3t/CD8t T-lymphocytes.Overall,the strategy of localized co-delivery of DOX/IL-2/IFN-g using the polypeptide hydrogel provided a promising approach for efficient melanoma therapy.
基金We thank the Beijing Talents Foundation(2017000021223ZK30)Beijing Lab Foundation+1 种基金Special Funds for COVID-19 Prevention and Control of West China Hospital of Sichuan University(HX-2019-nCoV-049)the National Key Research and Developm ent Program of China(SQ2020YFF0426498).
文摘Dear Editor,The coronavirus infectious disease 2019(COVID-19)outbreak is seriously endangering human health.Most patients with severe COVID-19 are characterized by sustained cytokine production and hyper-inflammation,which is known as cytokine storm syndrome.1-3 Elaborating the anti-inflammatory response is crucial to these patients,and interieukin-6(IL6)inhibitors and steroids have been recommended in clinical practice.1 However,after the cytokine storm phase,the host immune response to sepsis may develop into a protracted immunosuppressive phase.
基金supported by the National Natural Science Foundation of China(51472101,51572114,21773062,21577036)the Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials(JSKC17003)~~
文摘Silver nanoparticles (Ag NPs) can effectively address the issue of antibiotic-resistant bacterial infections to reduce the potential toxicity of Ag NPs. Although challenging, it is, therefore, necessary to achieve the sustainable release of Ag+ ions from a finite amount of Ag NPs. This study aims at designing an efficient and benign antimicrobial silver-based ternary composite composed of photocatalysis zinc oxide (ZnO) and reduced graphene oxide (rGO) as a carrier, in which the reactive oxygen species (ROS) excited from ZnO and Ag+ ions released from the Ag NPs cooperate to realize an effective antibacterial activity against E. coli and S. aureus. The constant effective bacterial performance of the ternary photocatalyst with minimum Ag content can be attributed to the increase in the available quantity of ROS, which results from the enhanced separation efficiency of the photogenerated carriers. The proposed system notably realized the long-term sustainable release of Ag+ ions with low concentration for 30 days when compared with an equivalent amount of silver nitrate. Moreover, the use of the composite prevents biotoxicity and silver wastage, and imparts enhanced stability to the long-lasting antibacterial efficacy.
