Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)...Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.展开更多
Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments h...Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.展开更多
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and th...Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.展开更多
In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex ...In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex interplay of genetic,epigenetic,and environmental factors.Key genetic alterations,such as mutations in TERT,TP53,and CTNNB1,alongside epigenetic modifications such as DNA methylation and histone remodeling,disrupt regulatory pathways and promote tumorigenesis.Environmental factors,including viral infections,alcohol consum-ption,and metabolic disorders such as nonalcoholic fatty liver disease,enhance hepatocarcinogenesis.The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance,with immune cell infiltration,fibrosis,and angiogenesis supporting cancer cell survival.Advances in immune check-point inhibitors and chimeric antigen receptor T-cell therapies have shown po-tential,but the unique immunosuppressive milieu in liver cancer presents challenges.Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies.Next-generation sequencing is accele-rating the identification of genetic and epigenetic alterations,enabling more precise diagnosis and personalized treatment plans.A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.展开更多
BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of h...BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of hyaluronic acid(HA)and type III procollagen N-peptide(PIIINP)with direct-acting antivirals treatment failure in Egyptian patients with chronic hepatitis C.METHODS Hepatitis C patients(responders and non-responders to sofosbuvir/daclatasvir)were tested for HA and PIIINP using sensitive chemiluminescent immunoassay.RESULTS There were distinctly higher PIIINP(P=0.0003)and HA(P<0.0001)levels in non-responders than responders patients with a good ability for distinguishing non-responders from patients with sustained virological response(area under the curve=0.766 for HA and 0.684 for PIIINP).Logistic regression analysis revealed that the HA×PIIINP is the model with the highest predictive ability(area under the curve=0.809).Diagnostic performances were superior to each marker alone with good sensitivity(74.7%),specificity(74%),positive predictive(68.3%),negative predictive values(79.6%)and accuracy(74.3%).The multiplication of HA×PIIINP is correlated significantly(P<0.05)with elevated liver enzymes(r=0.212),decreased albumin(r=-0.26),elevated aspartate aminotransferase-platelet ratio index(r=0.223)and elevated fibrosis-4 score(r=0.216)scores.CONCLUSION These findings suggested the remarkable role of fibrogensis markers HA and PIIINP in the prediction of hepatitis C virus DAAs treatment response.Multiplying HA with PIIINP values increase the sensitivity to detect treatment success and thus may aim to improve treatment duration and the disease control.展开更多
Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met th...Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.展开更多
The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup p...The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup physico-chemical evaluation such as pH, density, identification of polysaccharide, tanning agents, ascorbic acid and shelf life was complied. The TLC and quantitative determination of alkaloid were quantified. Determination of biomarker has been validated for the analysis of vasicine. The study result revealed that Linkus syrup formulation was well standardized at different levels such as physic-chemical consistency and assay of bio marker compound.展开更多
BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally de...BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.展开更多
Colorectal cancer is the second leading cause of cancer-related deaths in the United States.Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer,they become non-eff...Colorectal cancer is the second leading cause of cancer-related deaths in the United States.Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer,they become non-effective when the cancer progresses to an invasive stage.Since consumption of certain dietary agents has been linked with various cancers,fruit juices have been investigated for their consistently protective effect against colon cancer.The unique biochemical composition of fruit juices is responsible for their anticancer properties.In this review,the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed.For this purpose,the bioavailability,in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted.Moreover,there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer.This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer.展开更多
Acute pancreatitis(AP),chronic pancreatitis(CP)and pancreatic cancer are three distinct pancreatic diseases with different prognoses and treatment options.However,it may be difficult to differentiate between benign an...Acute pancreatitis(AP),chronic pancreatitis(CP)and pancreatic cancer are three distinct pancreatic diseases with different prognoses and treatment options.However,it may be difficult to differentiate between benign and malignant disease.AP may be a first symptom of pancreatic cancer,particularly in patients between the ages of 56 and 75 with presumed idiopathic AP who had a concomitant diagnosis of new-onset diabetes mellitus or patients who present with CP at diagnosis of AP.In these patients,additional imaging is warranted,preferably by endoscopic ultrasonography.CP may lead to pancreatic cancer through oncogenic mutations,mostly in patients with hereditary CP,and in patients in whom risk factors for pancreatic cancer(e.g.,nicotine and alcohol abuse)are also present.Patients with PRSS1-mediated CP and patients with a history of autosomal dominant hereditary CP without known genetic mutations may be considered for surveillance for pancreatic cancer.Pancreatic inflammation may mimic pancreatic cancer by appearing as a focal mass-forming lesion on imaging.Differentiation between the above mentioned benign and malignant disease may be facilitated by specific features like the duct-penetrating sign and the duct-to-parenchyma ratio.Research efforts are aimed towards developing a superior discriminant between pancreatitis and pancreatic cancer in the form of imaging modalities or biomarkers.This may aid clinicians in timely diagnosing pancreatic cancer in a potentially curable stage.展开更多
Colon cancer arises due to the conversion of precancerous polyps(benign)found in the inner lining of the colon.Prevention is better than cure,and this is very true with respect to colon cancer.Various epidemiologic st...Colon cancer arises due to the conversion of precancerous polyps(benign)found in the inner lining of the colon.Prevention is better than cure,and this is very true with respect to colon cancer.Various epidemiologic studies have linked colorectal cancer with food intake.Apple and berry juices are widely consumed among various ethnicities because of their nutritious values.In this review article,chemopreventive effects of these fruit juices against colon cancer are discussed.Studies dealing with bioavailability,in vitro and in vivo effects of apple and berry juices are emphasized in this article.A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines.This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells,and also strives to facilitate clinical studies using these juices in humans in large trials.The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.展开更多
Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The...Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified.The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time.The results showed that the morbidity associated with primary TBA has increased over recent years.The clinical manifestations were non-specific.Progressive dyspnea, cough and sputum were the most common symptoms.The percentage of patients undergoing computed tomography (CT) scan has increased over the years.The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis.Treatment was reported for a total of 44 cases.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients.It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries.Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s.Chest CT scan provides important clues for the diagnosis of the disease.The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.展开更多
Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional ...Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.展开更多
To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies us...To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.RESULTSUpregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSIONThese data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.展开更多
BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still e...BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.展开更多
AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature sea...AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios(OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen(HBs Ag) positive] were included. The comparison group consisted of HBs Agnegative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of Der Simonian and Laird. The protocol for this metaanalysis is registered with PROSPERO(International Prospective Register of Systematic Reviews; no. CRD42017080657).RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBs Ag-negative recipients, HBs Ag-positive status was significantly associated with increased risk of mortality after kidney transplantation(pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBs Ag-positive recipients and year of study(slopes =-0.062, P = 0.001). HBs Agpositive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46(95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure(slopes =-0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBs Ag-positive recipients, respectively.CONCLUSION Among kidney transplant patients, there are significant associations between HBs Ag-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBs Ag-positive recipients overtime.展开更多
Robust Parameter Design(RPD) has been widely applied for improving quality and reliability of products.One of the key drawbacks of applying RPD using Taguchi method is that the stable factors may not be independent of...Robust Parameter Design(RPD) has been widely applied for improving quality and reliability of products.One of the key drawbacks of applying RPD using Taguchi method is that the stable factors may not be independent of the adjustment factors, resulting in unsatisfactory design.Moreover, the Taguchi method cannot guarantee global optimality since the levels set in the experiment are usually discrete to ensure orthogonal design.In this paper, robust solutions of the stable factors are obtained via a nonlinear model based on polynomial fitting;while the adjustment factors are obtained via interactions analysis so that they are independent of the stable factors.In particular, the values of the adjustment factors are determined by output offset compensation so as to achieve robustness of the design scheme.An example on the design of an aeronautical electrical apparatus is presented to illustrate the procedure.The results show that the proposed method can take full advantage of the nonlinearity in the response and achieve the desired outcome.展开更多
Neurovascular interactions are crucial for the normal development of the central nervous system. To study such interactions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and...Neurovascular interactions are crucial for the normal development of the central nervous system. To study such interactions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelial cell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favor maintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differentiation of neural progenitors through direct contact. These apparently opposing effects could reflect differential cellular interactions needed for the proper development of the brain.展开更多
The maritime industry is currently facing the challenges of adopting new technologies and operational practices with stricter international, national and local rules in order to reduce exhaust gas emissions from ships...The maritime industry is currently facing the challenges of adopting new technologies and operational practices with stricter international, national and local rules in order to reduce exhaust gas emissions from ships. The most objective of regulations introduced and presented by the Worldwide Sea Organization such as International Maritime Organization (IMO) and the US Environmental Protection Agency (EPA) is to lessen the commitment shipping makes to worldwide and local discharges. This paper analyzes emissions from marine engines and the process of waste exhaust gas formation and provides a summary of the emission reduction technologies to satisfy MARPOL NOx tier III and EPA tier IV rules. The results showed the possibility of achieving a valuable emission reduction percentage if future diesel engines are equipped with pre-treatment, internal-treatment and/or post-treatment techniques. Economics impact for medium and low speed for category 3 marine diesel engines is also presented.展开更多
基金Bu-Ali Sina University for providing financial support for conducting this study。
文摘Density(p),speed of sound(u),viscosity(η),and refractive index(n_(D))were measured for pure acetonitrile,trichloroethene,and tetrachloroethene,as well as their binary mixtures at temperatures T=(293.15,298.15,303.15)K and at ambient pressure(81.5 kPa).From the experimental data,excess molar volume(V_(m)~E),thermal expansion coefficients(α),deviations in isentropic compressibility(Δκ_(S)),viscosity(Δ_η),and refractive index(Δn_(D))were calculated.These values were then correlated using the Redlich-Kister polynomial equation,with fitting coefficients and standard deviations determined.Additionally,the Prigogine-Flory-Patterson(PFP)theory and the Extended Real Associated Solution(ERAS)model were employed to correlate the excess molar volume,while the Perturbed Chain Statistical Associating Fluid Theory(PC-SAFT)was used to predict the density of mixtures.
文摘Sugarcane bagasse(SCB)is a promising natural fiber for bio-based composites,but its high moisture absorption and poor interfacial adhesion with polymer matrices limit mechanical performance.While chemical treatments have been extensively explored,limited research has addressed how thermal treatment alone alters the surface properties and reinforcing behavior of SCB fibers.This study aims to fill that gap by investigating the effects of heat treatment on SCB fiber structure and its performance in starch/poly(vinyl alcohol)(PVA)composites.Characterization techniques including Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),X-ray photoelectron spectroscopy(XPS),and scanning electron microscopy(SEM)were employed to analyze changes in fiber morphology,surface chemistry,and crystallinity.Mechanical properties were assessed via tensile,flexural,and impact testing,and moisture absorption was also evaluated.Composites reinforced with SCB fibers treated at 200○C exhibited significantly superior mechanical properties compared to those prepared with untreated or differently treated fibers.The tensile,flexural,and impact performance of the composites were 15.13,19.37 MPa,and 7.28 J/m,respectively.Composites treated at this temperature also retained better mechanical properties after exposure to humidity.These findings demonstrate that heat treatment is a simple and sustainable method to improve the durability and mechanical performance of nature fiber-reinforced composites,expanding their potential for environmentally friendly material applications.
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
文摘Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.
文摘In this review,we explore the application of next-generation sequencing in liver cancer research,highlighting its potential in modern oncology.Liver cancer,particularly hepatocellular carcinoma,is driven by a complex interplay of genetic,epigenetic,and environmental factors.Key genetic alterations,such as mutations in TERT,TP53,and CTNNB1,alongside epigenetic modifications such as DNA methylation and histone remodeling,disrupt regulatory pathways and promote tumorigenesis.Environmental factors,including viral infections,alcohol consum-ption,and metabolic disorders such as nonalcoholic fatty liver disease,enhance hepatocarcinogenesis.The tumor microenvironment plays a pivotal role in liver cancer progression and therapy resistance,with immune cell infiltration,fibrosis,and angiogenesis supporting cancer cell survival.Advances in immune check-point inhibitors and chimeric antigen receptor T-cell therapies have shown po-tential,but the unique immunosuppressive milieu in liver cancer presents challenges.Dysregulation in pathways such as Wnt/β-catenin underscores the need for targeted therapeutic strategies.Next-generation sequencing is accele-rating the identification of genetic and epigenetic alterations,enabling more precise diagnosis and personalized treatment plans.A deeper understanding of these molecular mechanisms is essential for advancing early detection and developing effective therapies against liver cancer.
文摘BACKGROUND Treatment response to direct-acting antivirals(DAAs)is a challenging issue and the identification of non-responders patients is very important.AIM To evaluate the relation between baseline serum levels of hyaluronic acid(HA)and type III procollagen N-peptide(PIIINP)with direct-acting antivirals treatment failure in Egyptian patients with chronic hepatitis C.METHODS Hepatitis C patients(responders and non-responders to sofosbuvir/daclatasvir)were tested for HA and PIIINP using sensitive chemiluminescent immunoassay.RESULTS There were distinctly higher PIIINP(P=0.0003)and HA(P<0.0001)levels in non-responders than responders patients with a good ability for distinguishing non-responders from patients with sustained virological response(area under the curve=0.766 for HA and 0.684 for PIIINP).Logistic regression analysis revealed that the HA×PIIINP is the model with the highest predictive ability(area under the curve=0.809).Diagnostic performances were superior to each marker alone with good sensitivity(74.7%),specificity(74%),positive predictive(68.3%),negative predictive values(79.6%)and accuracy(74.3%).The multiplication of HA×PIIINP is correlated significantly(P<0.05)with elevated liver enzymes(r=0.212),decreased albumin(r=-0.26),elevated aspartate aminotransferase-platelet ratio index(r=0.223)and elevated fibrosis-4 score(r=0.216)scores.CONCLUSION These findings suggested the remarkable role of fibrogensis markers HA and PIIINP in the prediction of hepatitis C virus DAAs treatment response.Multiplying HA with PIIINP values increase the sensitivity to detect treatment success and thus may aim to improve treatment duration and the disease control.
基金supported by the Razi Vaccine and Serum Research Institute(RVSRI)Karaj,Iran,(No.17-18-18-063-01047-011130).
文摘Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.
文摘The present work has been carried out on polyherbal formulation named as Linkus Syrup. The herbal formulation consists of Glycyrrhiza glabra, Hyssopus officinalis, Piper longum and Alpinia galangal. The Linkus syrup physico-chemical evaluation such as pH, density, identification of polysaccharide, tanning agents, ascorbic acid and shelf life was complied. The TLC and quantitative determination of alkaloid were quantified. Determination of biomarker has been validated for the analysis of vasicine. The study result revealed that Linkus syrup formulation was well standardized at different levels such as physic-chemical consistency and assay of bio marker compound.
文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.
文摘Colorectal cancer is the second leading cause of cancer-related deaths in the United States.Recent studies prove that though chemotherapeutic agents are being used for the treatment of colon cancer,they become non-effective when the cancer progresses to an invasive stage.Since consumption of certain dietary agents has been linked with various cancers,fruit juices have been investigated for their consistently protective effect against colon cancer.The unique biochemical composition of fruit juices is responsible for their anticancer properties.In this review,the chemo-preventive effect of fruit juices such as pomegranate and citrus juices against colon cancer are discussed.For this purpose,the bioavailability,in vitro and in vivo effects of these fruit juices on colorectal cancer are highlighted.Moreover,there is a scarcity of studies involving human trials to estimate the preventive nature of these juices against colon cancer.This review will support the need for more preclinical tests with these crude juices and their constituents in different colorectal cancer cell lines and also some epidemiological studies in order to have a better understanding and promote pomegranate and citrus juices as crusaders against colon cancer.
文摘Acute pancreatitis(AP),chronic pancreatitis(CP)and pancreatic cancer are three distinct pancreatic diseases with different prognoses and treatment options.However,it may be difficult to differentiate between benign and malignant disease.AP may be a first symptom of pancreatic cancer,particularly in patients between the ages of 56 and 75 with presumed idiopathic AP who had a concomitant diagnosis of new-onset diabetes mellitus or patients who present with CP at diagnosis of AP.In these patients,additional imaging is warranted,preferably by endoscopic ultrasonography.CP may lead to pancreatic cancer through oncogenic mutations,mostly in patients with hereditary CP,and in patients in whom risk factors for pancreatic cancer(e.g.,nicotine and alcohol abuse)are also present.Patients with PRSS1-mediated CP and patients with a history of autosomal dominant hereditary CP without known genetic mutations may be considered for surveillance for pancreatic cancer.Pancreatic inflammation may mimic pancreatic cancer by appearing as a focal mass-forming lesion on imaging.Differentiation between the above mentioned benign and malignant disease may be facilitated by specific features like the duct-penetrating sign and the duct-to-parenchyma ratio.Research efforts are aimed towards developing a superior discriminant between pancreatitis and pancreatic cancer in the form of imaging modalities or biomarkers.This may aid clinicians in timely diagnosing pancreatic cancer in a potentially curable stage.
基金Supported by(in part)Ministry of Higher Education Malaysia with the Grant Vot,No.R.J130000.7809.4F444 and the Ref No.PY/2014/03167Part of the grant with the Vot,No.04H93,Ministry of Education was also used for this study
文摘Colon cancer arises due to the conversion of precancerous polyps(benign)found in the inner lining of the colon.Prevention is better than cure,and this is very true with respect to colon cancer.Various epidemiologic studies have linked colorectal cancer with food intake.Apple and berry juices are widely consumed among various ethnicities because of their nutritious values.In this review article,chemopreventive effects of these fruit juices against colon cancer are discussed.Studies dealing with bioavailability,in vitro and in vivo effects of apple and berry juices are emphasized in this article.A thorough literature survey indicated that various phenolic phytochemicals present in these fruit juices have the innate potential to inhibit colon cancer cell lines.This review proposes the need for more preclinical evidence for the effects of fruit juices against different colon cancer cells,and also strives to facilitate clinical studies using these juices in humans in large trials.The conclusion of the review is that these apple and berry juices will be possible candidates in the campaign against colon cancer.
基金supported by the grants from Natural Science Foundation of Zhejiang Province (No.Y2080323)Zhejiang Provincial Science and Technology Administration (No.2009R100310 and No.2008C03002-2)Health Department of Zhejiang Province (No.2009QN010)
文摘Primary tracheobronchial amyloidosis (TBA) is a rare pulmonary disease.A systematic review was performed on 64 cases of primary TBA in China and progress in the diagnosis and treatment of this disease is discussed.The Chinese biological and medical databases from 1970 to 2010 were searched and 75 cases of complete clinical and pathological data were identified.The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time.The results showed that the morbidity associated with primary TBA has increased over recent years.The clinical manifestations were non-specific.Progressive dyspnea, cough and sputum were the most common symptoms.The percentage of patients undergoing computed tomography (CT) scan has increased over the years.The bronchoscopy and transbrochial lung biopsy (TBLB) were usually sufficient to establish the diagnosis.Treatment was reported for a total of 44 cases.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration such as steroids and colchicines were reported to be effective in some patients.It is concluded that the demographic characteristics and clinical manifestations of primary TBA patients in China are largely consistent with findings reported in other countries.Dramatically more cases were reported in recent years, mainly due to the extensive application of bronchoscopy since 1990s.Chest CT scan provides important clues for the diagnosis of the disease.The definite diagnosis was confirmed by bronchoscopic findings and Congo red staining of biopsy specimen.Bronchoscopic Nd:YAG laser irradiation, argon plasma coagulation (APC) and drugs administration, such as steroids and colchicines were reported to be effective in some patients.
基金partially supported by the National Natural Science Foundation of China(No.82473256)the Jiangxi Provincial Natural Science Foundation,China(No.20242BAB25521)+7 种基金Ganpo Promising Talents Supporting Plan—Talent Development Project of Leading Academic and Technological Researchers in Key Disciplines(No.20243BCE51060)the Anhui Province Higher Education Scientific Research Project,China(No.2024AH050818)the Anhui Provincial Natural Science Foundation,China(No.2208085MH251)the Fundamental Research Funds for the Anhui Medical University,China(No.2021xkj131)the Research Fund of Anhui Institute of Translational Medicine,China(No.2023zhyx-C19)the Health Research Program of Anhui,China(No.AHWJ2023A30007)the Anhui Provincial Department of Education,Provincial Quality Engineering Project for Higher Education(Nos.2022jyxm761 and 2023jyxm1106)the Basic and Clinical Cooperative Research and Promotion Program of the Anhui Medical University,China(No.2022xkj T024)。
文摘Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.
文摘To evaluate a calcium activated potassium channel (KCa3.1) inhibitor attenuates liver disease in models of non-alcoholic fatty liver disease (NAFLD).METHODSWe have performed a series of in vitro and in vivo studies using the KCa3.1 channel inhibitor, Senicapoc. Efficacy studies of Senicapoc were conducted in toxin-, thioacetamide (TAA) and high fat diet (HFD)-induced models of liver fibrosis in rats. Efficacy and pharmacodynamic effects of Senicapoc was determined through biomarkers of apoptosis, inflammation, steatosis and fibrosis.RESULTSUpregulation of KCa3.1 expression was recorded in TAA-induced and high fat diet-induced liver disease. Treatment with Senicapoc decreased palmitic acid-driven HepG2 cell death. (P < 0.05 vs control) supporting the finding that Senicapoc reduces lipid-driven apoptosis in HepG2 cell cultures. In animals fed a HFD for 6 wk, co-treatment with Senicapoc, (1) reduced non-alcoholic fatty liver disease (NAFLD) activity score (NAS) (0-8 scale), (2) decreased steatosis and (3) decreased hepatic lipid content (Oil Red O, P < 0.05 vs vehicle). Randomization of TAA animals and HFD fed animals to Senicapoc was associated with a decrease in liver fibrosis as evidenced by hydroxyproline and Masson’s trichrome staining (P < 0.05 vs vehicle). These results demonstrated that Senicapoc mitigates both steatosis and fibrosis in liver fibrosis models.CONCLUSIONThese data suggest that Senicapoc interrupts more than one node in progressive fatty liver disease by its anti-steatotic and anti-fibrotic activities, serving as a double-edged therapeutic sword.
基金Supported by National Science and Technology Major Project,No.2014ZX09101046-004(to Chen L)National Natural Science Foundation of China,Nos.81873543 and 81570468(to Wang JS).
文摘BACKGROUND Mannosyl-oligosaccharide glucosidase(MOGS)deficiency is an extremely rare type of congenital disorder of glycosylation(CDG),with only 12 reported cases.Its clinical,genetic,and glycomic features are still expanding.Our aim is to update the novel clinical and glycosylation features of 2 previously reported patients with MOGS-CDG.CASE SUMMARY We collected comprehensive clinical information,and conducted the immunoglobulin G1 glycosylation assay using nano-electrospray ionization source quadruple time-of-flight mass spectrometry.Novel dysmorphic features included an enlarged tongue,forwardly rotated earlobes,a birth mark,overlapped toes,and abnormal fat distribution.Novel imaging findings included pericardial effusion,a deep interarytenoid groove,mild congenital subglottic stenosis,and laryngomalacia.Novel laboratory findings included peripheral leukocytosis with neutrophil predominance,elevated C-reactive protein and creatine kinase,dyslipidemia,coagulopathy,complement 3 and complement 4 deficiencies,decreased proportions of T lymphocytes and natural killer cells,and increased serum interleukin 6.Glycosylation studies showed a significant increase of hypermannosylated glycopeptides(Glc3Man7GlcNAc2/N2H10 and Man5GlcNAc2/N2H5)and hypersialylated glycopeptides.A compensatory glycosylation pathway leading to an increase in Man5GlcNAc2/N2H5 was indicated with the glycosylation profile.CONCLUSION We confirmed abnormal glycomics in 1 patient,expanding the clinical and glycomic spectrum of MOGS-CDG.We also postulated a compensatory glycosylation pathway,leading to a possible serum biomarker for future diagnosis.
文摘AIM To assess outcomes of kidney transplantation including patient and allograft outcomes in recipients with hepatitis B virus(HBV) infection, and the trends of patient's outcomes overtime.METHODS A literature search was conducted using MEDLINE, EMBASE and Cochrane Database from inception through October 2017. Studies that reported odds ratios(OR) of mortality or renal allograft failure after kidney transplantation in patients with HBV [defined as hepatitis B surface antigen(HBs Ag) positive] were included. The comparison group consisted of HBs Agnegative kidney transplant recipients. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of Der Simonian and Laird. The protocol for this metaanalysis is registered with PROSPERO(International Prospective Register of Systematic Reviews; no. CRD42017080657).RESULTS Ten observational studies with a total of 87623 kidney transplant patients were enrolled. Compared to HBs Ag-negative recipients, HBs Ag-positive status was significantly associated with increased risk of mortality after kidney transplantation(pooled OR = 2.48; 95%CI: 1.61-3.83). Meta-regression showed significant negative correlations between mortality risk after kidney transplantation in HBs Ag-positive recipients and year of study(slopes =-0.062, P = 0.001). HBs Agpositive status was also associated with increased risk of renal allograft failure with pooled OR of 1.46(95%CI: 1.08-1.96). There was also a significant negative correlation between year of study and risk of allograft failure(slopes =-0.018, P = 0.002). These associations existed in overall analysis as well as in limited cohort of hepatitis C virus-negative patients. We found no publication bias as assessed by the funnel plots and Egger's regression asymmetry test with P = 0.18 and 0.13 for the risks of mortality and allograft failure after kidney transplantation in HBs Ag-positive recipients, respectively.CONCLUSION Among kidney transplant patients, there are significant associations between HBs Ag-positive status and poor outcomes including mortality and allograft failure. However, there are potential improvements in patient and graft survivals in HBs Ag-positive recipients overtime.
基金co-supported by the National Natural Science Foundation of China(Nos.51707044 and 61671172)the China Postdoctoral Science Foundation(No.2018M632377)。
文摘Robust Parameter Design(RPD) has been widely applied for improving quality and reliability of products.One of the key drawbacks of applying RPD using Taguchi method is that the stable factors may not be independent of the adjustment factors, resulting in unsatisfactory design.Moreover, the Taguchi method cannot guarantee global optimality since the levels set in the experiment are usually discrete to ensure orthogonal design.In this paper, robust solutions of the stable factors are obtained via a nonlinear model based on polynomial fitting;while the adjustment factors are obtained via interactions analysis so that they are independent of the stable factors.In particular, the values of the adjustment factors are determined by output offset compensation so as to achieve robustness of the design scheme.An example on the design of an aeronautical electrical apparatus is presented to illustrate the procedure.The results show that the proposed method can take full advantage of the nonlinearity in the response and achieve the desired outcome.
文摘Neurovascular interactions are crucial for the normal development of the central nervous system. To study such interactions in primary cultures, we developed a procedure to simultaneously isolate neural progenitor and endothelial cell fractions from embryonic mouse brains. Depending on the culture conditions endothelial cells were found to favor maintenance of the neuroprogenitor phenotype through the production of soluble factors, or to promote neuronal differentiation of neural progenitors through direct contact. These apparently opposing effects could reflect differential cellular interactions needed for the proper development of the brain.
文摘The maritime industry is currently facing the challenges of adopting new technologies and operational practices with stricter international, national and local rules in order to reduce exhaust gas emissions from ships. The most objective of regulations introduced and presented by the Worldwide Sea Organization such as International Maritime Organization (IMO) and the US Environmental Protection Agency (EPA) is to lessen the commitment shipping makes to worldwide and local discharges. This paper analyzes emissions from marine engines and the process of waste exhaust gas formation and provides a summary of the emission reduction technologies to satisfy MARPOL NOx tier III and EPA tier IV rules. The results showed the possibility of achieving a valuable emission reduction percentage if future diesel engines are equipped with pre-treatment, internal-treatment and/or post-treatment techniques. Economics impact for medium and low speed for category 3 marine diesel engines is also presented.
