AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI a...AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS： It is an international multicenter study, and there were 12 centres and 125 patients （64 males, 61 females, aged 59 ± 11 years） involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a Iow-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS： CEUS with SonoVue increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS （55）, triple-phase spiral CT （61） and HRI with a liverspecific contrast agent （53）. Accuracy of detection of metastatic disease （i.e. at least one metastatic lesion） was significantly higher for CEUS （91.2%） than for unenhanced sonography （81.4%） and was similar to that of triple-phase spiral CT （89.2 %）. In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients （94.4%）. CONCLUSION： CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.展开更多
AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal ...AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.展开更多
Background:Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing process.The molecular mechanisms driving keloid pathology remain incompletely understood,hin...Background:Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing process.The molecular mechanisms driving keloid pathology remain incompletely understood,hindering development of targeted,effective therapies.Recent studies in our laboratory demonstrated that keloid keratinocytes exhibit adhesion abnormalities and display a transcriptional signature reminiscent of cells undergoing epithelial-mesenchymal transition(EMT),suggesting a role for EMT in keloid pathology.In the current study,we further define the EMT-like phenotype of keloid scars and investigate regulation of EMT-related genes in keloid.Methods:Primary keratinocytes from keloid scar and normal skin were cultured in the presence or absence of transforming growth factor beta 1(TGF-β1)+/-inhibitors of TGF-β1 and downstream signaling pathways.Gene expression was measured using quantitative polymerase chain reaction.Migration was analyzed using an in vitro wound healing assay.Proteins in keloid scar and normal skin sections were localized by immunohistochemistry.Statistical analyses utilized SigmaPlot(SyStat Software,San Jose,CA)or SAS?(SAS Institute,Cary,NC).Results:In keloid and normal keratinocytes,TGF-β1 regulated expression of EMT-related genes,including hyaluronan synthase 2,vimentin,cadherin-11,wingless-type MMTV integration site family,member 5A,frizzled 7,ADAM metallopeptidase domain 19,and interleukin-6.Inhibition of canonical TGF-β1 signaling in keloid keratinocytes significantly inhibited expression of these genes,and TGF-β1 stimulation of normal keratinocytes increased their expression.The inhibition of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway or the p38 mitogen-activated protein kinase pathway attenuated TGF-β1-induced expression of subsets of these genes.Migration of keloid keratinocytes,previously shown to be increased compared with normal keratinocytes,was significantly reduced by inhibition of TGF-β1 or ERK1/2 signaling.Biomarkers of EMT,includi展开更多
AIM:To investigated the incidence of diversion colitis(DC) and impact of DC symptoms on quality of life(QoL) after ileostomy reversal in rectal cancer.METHODS:We performed a prospective study with 30 patients who unde...AIM:To investigated the incidence of diversion colitis(DC) and impact of DC symptoms on quality of life(QoL) after ileostomy reversal in rectal cancer.METHODS:We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery,Korea University Anam Hospital.The participants totally underwent two rounds of the examinations.At first examination,endoscopies,tissue biopsies,and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations.At second examination,endoscopies,tissue biopsies,and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals.Clinicopathological data were based on the histopathological reports and clinical records of the patients.RESULTS:At the first examination,all of the patients presented with inflammation,which was mild in 15(50%) patients,moderate in 11(36.7%) and severe in 4(13.3%) by endoscopy and mild in 14(46.7%) and moderate in 16(53.3%) by histology.At the second examination,only 11(36.7%) and 17(56.7%) patients had mild inflammation by endoscopy and histology,respectively.There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination.The symptoms detected on the first and second questionnaires were mucous discharge in 12(40%) and 5(17%) patients,bloody discharge in 5(17%) and 3(10%) patients,abdominal pain in 4(13%) and 2(7%) patients and tenesmus in 9(30%) and 5(17%) patients,respectively.We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge,bleeding,abdominal pain and tenesmus in both time points.Diarrhea was detected in 9 patients at the second examination;this number correlated with the severity of DC(0%,0%,66.7%,33.3% vs 0%,71.4%,23.8%,4.8%,P = 0.001) and the symptom-related QoL(r =-0.791,P < 0.001).CONCLUSION:The severity of DC is relate展开更多
For phosphorus （P） recovery from wastewater, the effect of humic substances （HS） on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with syn...For phosphorus （P） recovery from wastewater, the effect of humic substances （HS） on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate （as P） and 20 mg/L HS （as dissolved organic carbon, DOC） at a constant pH value in the range of 8.0-10.0. The concentration variations of phosphate, calcium （Ca） and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction （XRD） and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH ≥9.0, the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations ≤3.5 mg/L, and at pH ≥ 9.0 and HS concentrations ≤ 10 mg/L, the final precipitates were proved to be hydroxyapatite （HAP） by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate.展开更多
Aims Positive plant diversity-ecosystem function relations are ultimately driven by variation in functional traits among individuals that form a community.To date,research has largely focused on the role of species di...Aims Positive plant diversity-ecosystem function relations are ultimately driven by variation in functional traits among individuals that form a community.To date,research has largely focused on the role of species diversity for ecosystem functioning.However,substantial intraspecific trait variation is common and a significant part of this variation caused by genetic differences among individuals.Here,we studied the relative importance of species diversity and seed family(SF)diversity within species for growth and herbivory in experimental subtropical tree assemblages.Methods In 2010,we set up a field experiment in subtropical China,using four species from the local species pool.Trees were raised from seeds,with seeds from the same mother tree forming an SF.We established 23 plots containing one or four species(species diversity treatment)and one or four SFs per species(SF diversity treatment).Tree growth(stem diameter,plant height and crown expansion)and herbivory(percentage leaf loss due to leaf chewers)were monitored annually from 2011 to 2013.Important findings Tree species richness promoted growth but had no effect on herbivory.In contrast,SF diversity reduced growth and increased herbivory but only so in species mixtures.Most of the observed effects were time dependent,with the largest effect found in 2013.Our results suggest that biodiversity can affect plant performance directly via tree species-species interactions,or context dependent,via potential effects on inter-trophic interactions.Two important conclusions should be drawn from our findings.Firstly,in future studies regarding biodiversity and ecosystem functioning(BEF)relationships,intraspecific genetic diversity should be given similar weight as species diversity as it has often been neglected and its effects are not well understood.Secondly,we demonstrate opposite effects of biodiversity among and within species,stressing the importance to consider the effects of multiple levels of biodiversity simultaneously.展开更多
AIM： To identify multi-detector computed tomography （MDCT） features most predictive of serous cystadenomas （SCAs）, correlating with histopathology, and to study the impact of cyst size and MDCT technique on reade...AIM： To identify multi-detector computed tomography （MDCT） features most predictive of serous cystadenomas （SCAs）, correlating with histopathology, and to study the impact of cyst size and MDCT technique on reader performance. METHODS： The MDCT scans of 164 patients with surgically verified pancreatic cystic lesions were reviewed by two readers to study the predictive value of various morphological features for establishing a diagnosis of SCAs. Accuracy in lesion characterization and reader confidence were correlated with lesion size （≤3 cm or 〉≥3 cm） and scanning protocols （dedicated vs routine）. RESULTS： 28/164 cysts （mean size, 39 mm; range, 8-92 mm） were diagnosed as SCA on pathology. The MDCT features predictive of diagnosis of SCA were microcystic appearance （22/28, 78.6%）, surface Iobulations （25/28, 89.3%） and central scar （9/28, 32.4%）. Stepwise logistic regression analysis showed that only microcystic appearance was significant for CT diagnosis of SCA （P = 0.0001）. The sensitivity, specificity and PPV of central scar and of combined microcystic appearance and Iobulations were 32.4%/100%/100% and 68%/100%/100%, respectively. The reader confidence was higher for lesions 〉 3 cm （P = 0.02） and for MDCT scans performed using thin collimation （1.25-2.5 mm） compared to routine 5 mm collimation exams （P 〉 0.05）. CONCLUSION： Central scar on MDCT is diagnostic of SCA but is seen in only one third of SCAs. Microcystic morphology is the most significant CT feature in diagnosis of SCA. A combination of microcystic appearance and surface Iobulations offers accuracy comparable to central scar with higher sensitivity.展开更多
Foreign bodies in the colon are encountered with increasing frequency, but only sporadic reports concerning their management have appeared in the literature. While most ingested foreign bodies usually pass through the...Foreign bodies in the colon are encountered with increasing frequency, but only sporadic reports concerning their management have appeared in the literature. While most ingested foreign bodies usually pass through the gastrointestinal tract uneventfully, sharp foreign bodies such as toothpicks infrequently cause intestinal perforation and may even result in death. We report our experience with a patient with a sigmoid colon pseudodiverticulum formation, a complication of accidental ingestion of a toothpick that was diagnosed and successfully managed colonoscopically.展开更多
AIM： Pathological prion protein （PrP^sc） is responsible for the development of transmissible spongiform encephalopathies （TSE）. While PrPc enters the organism via the oral route, less data is available to know ab...AIM： Pathological prion protein （PrP^sc） is responsible for the development of transmissible spongiform encephalopathies （TSE）. While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of priori precursor PrPc, which is constitutively expressed in the gastric mucosa.METHODS： We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting. The effect of central mediators of gastric inflammation, i.e., gastrin, prostaglandin E2 （PGE2）, tumor necrosis factor alpha （TNF-α） and interleukin 1 beta （IL-1β） on PrPc expression was analyzed in gastric cell lines.RESULTS： PrPc expression was increased in H pyloriinfection compared with non-infected controls and decreased to normal after successful eradication. Gastrin, PGE2, and IL-1β dose-dependently upregulated PrPc in gastric cells, while TNF-α had no effect.CONCLUSION： H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE2 and IL-1β synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.展开更多
Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health protection.Within this context,waveguide-(WG)-based optical biosensors on the...Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health protection.Within this context,waveguide-(WG)-based optical biosensors on the siliconnitride(Si_(3)N_(4))platform represent a particularly promising option,offering highly sensitive detection of indicative biomarkers in multiplexed sensor arrays operated by light in the visible-wavelength range.However,while passive Si_(3)N_(4)-based photonic circuits lend themselves to highly scalable mass production,the integration of low-cost light sources remains a challenge.In this paper,we demonstrate optical biosensors that combine Si_(3)N_(4)sensor circuits with hybrid on-chip organic lasers.These Si_(3)N_(4)-organic hybrid(SiNOH)lasers rely on a dye-doped cladding material that are deposited on top of a passive WG and that are optically pumped by an external light source.Fabrication of the devices is simple:The underlying Si_(3)N_(4)WGs are structured in a single lithography step,and the organic gain medium is subsequently applied by dispensing,spin-coating,or ink-jet printing processes.A highly parallel read-out of the optical sensor signals is accomplished with a simple camera.In our proof-of-concept experiment,we demonstrate the viability of the approach by detecting different concentrations of fibrinogen in phosphate-buffered saline solutions with a sensor-length(L-)-related sensitivity of S/L=0.16 rad nM^(-1)mm^(-1).To our knowledge,this is the first demonstration of an integrated optical circuit driven by a co-integrated low-cost organic light source.We expect that the versatility of the device concept,the simple operation principle,and the compatibility with cost-efficient mass production will make the concept a highly attractive option for applications in biophotonics and point-of-care diagnostics.展开更多
MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with inter...MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.展开更多
This work presents an enhanced hydrometallurgical process for recycling lithium ion batteries. First, endof-life batteries were processed in a physical pre-treatment plant to obtain a representative electrode material...This work presents an enhanced hydrometallurgical process for recycling lithium ion batteries. First, endof-life batteries were processed in a physical pre-treatment plant to obtain a representative electrode material. The resulting leachate was purified forth by iron-precipitation, liquid–liquid extractions, and an innovative Li–Na separation, in order to obtain valuable products. These products include high-grade graphite, cobalt oxide(Co3O4, purity 83%), cobalt oxalate(CoC2O4, purity 96%), nickel oxide(Ni O, purity89%), and lithium carbonate(Li2CO3, purity 99.8%). The recovery rate was quantitative for graphite, between 80% and 85% for cobalt depending on the nature of the recovery method, 90% for nickel, and 72%for lithium. Secondary streams were also valorized to obtain sodium sulfate(Na2SO4, purity 96%), and MnCoFe2O4 magnetic nano-sorbents according to the zero-waste concept. In order to close the loop, recycled Co3O4 and NiO were used as conversion-type anode materials for advanced lithium ion batteries showing promising performances.展开更多
AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraff inembedded speci...AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraff inembedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cells. In each case, three core biopsies with a diameter of 2 mm were punched out and positioned in a recipient paraff in array block. Four-μm sections of these tissue array blocks were used for immunohistochemical analysis of protein S100A4, E-cadherin, and p53. Clinicopathological data were based on the original histopathologic reports and clinical records of patients. RESULTS: In normal colorectal mucosa, protein S100A4 immunoreactivity was clearly absent in both cytoplasm and nucleus. However, positive immunoreactivity of protein S100A4 was detected in 45 (35.4%) of the tumor cases. There was no significant association between positive immunoreactivity of protein S100A4 and clinicopathological parameters such as tumor differentiation or TNM stage, and also no correlation between the reactivity and E-cadherin or p53 expression. However, positive immunoreactivity of protein S100A4 was found to be associated with tumor recurrence (P = 0.004), and was also associated with significantly worse overall survival in the Kaplan-Meyer survival analysis (P = 0.044). After adjustment for tumor differentiation, tumor depth and nodal status, however, it failed to achieve statistical significance (P = 0.067). CONCLUSION: The expression of protein S100A4 is associated with tumor recurrence and poor overall survival in patients with colorectal cancer.展开更多
Plants are a rich source of valuable secondary metabolites and in the recent years plant cell, tissue and organ cultures have been developed as an important alternative sources for the production of these compounds. A...Plants are a rich source of valuable secondary metabolites and in the recent years plant cell, tissue and organ cultures have been developed as an important alternative sources for the production of these compounds. Adventitious roots have been successfully induced in many plant species and cultured for the production of high value secondary metabolites of pharmaceutical, nutraceutical and industrial importance. Adoption of elicitation methods have shown improved synthesis of secondary metabolites in adventitious root cultures. Development of large-scale culture methods using bioreactors has opened up feasibilities of production of secondary metabolites at the industrial levels. In the present review we summarize the progress made in recent past in the area of adventitious root cultures for the production of secondary metabolites.展开更多
Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduce...Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.展开更多
Complete mesocolic excision is a relatively new concept in western literature. It follows the same concept of total mesorectal excision and units’ routinely performing complete mesocolic excisions have goo...Complete mesocolic excision is a relatively new concept in western literature. It follows the same concept of total mesorectal excision and units’ routinely performing complete mesocolic excisions have good pathological results as well as good improvements in overall survival, disease free survival and local recurrence. And yet unlike total mesorectal excision, uptake in the West has been relatively slow with many units sceptical of the true benefits gained by taking up a more technically challenging and potentially more morbid procedure when there is a paucity of literature to support these claims. This article reviews complete mesocolic excision for colon cancer, attempting to identify the risks and benefits of the technique and particularly looking at the reasons why its uptake has not been universal. It also discusses the similarities of a complete mesocolic excision to a colon resection with a D3 lymphadenectomy as well as the role of a laparoscopic approach to this technique. Considering a D3 lymphadenectomy has been the standard of care for stage II and III colon cancers in many of our Asian neighbours for over 20 years, combining this data with data on complete mesocolic excision may provide enough evidence to support or refute the need for complete mesocolic excisions. Maybe there might be lessons to be learnt from our colleagues in the east.展开更多
As a new class of two-dimensional materials, two-dimensional (2D) heterostructures constructed from metal chalcogenides (MCs) have been gaining tremendous attention due to their unprecedented physical and chemical phe...As a new class of two-dimensional materials, two-dimensional (2D) heterostructures constructed from metal chalcogenides (MCs) have been gaining tremendous attention due to their unprecedented physical and chemical phenomena, mainly originated from their distinct structural features such as composition, architecture type, spatial arrangement of each component, crystal structure, exposed facet and interface, dimensionality in their heterostructures. Towards the realization of practical applications, synthetic approaches need a rational design with a variety of architecture types including laterally-combined, vertically-aligned, and conformally-coated 2D MC heterostructures. Among various synthetic routes, solution-based synthesis is thought of as an alternative to fabrication through high-cost setups since it can control those structural features in a cheap fashion. This review presents recent progress on solution-based synthesis to produce various 2D MC heterostructures with a focus on the synthetic fundamentals in terms of thermodynamic and kinetic aspects related to the growth mechanism. Four different synthetic approaches are reviewed: seeded growth, cation exchange reaction, colloidal atomic layer deposition, direct synthesis including one-step process and modified electrochemical method. We also provide some representative applications of 2D MC heterostructures and their hybrid composites in various fields including optoelectronics, thermoelectrics, catalysis, and battery. Finally, we offer an insight into challenges and future directions in a synthetic improvement of 2D MC heterostructures.展开更多
文摘AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS： It is an international multicenter study, and there were 12 centres and 125 patients （64 males, 61 females, aged 59 ± 11 years） involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a Iow-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS： CEUS with SonoVue increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS （55）, triple-phase spiral CT （61） and HRI with a liverspecific contrast agent （53）. Accuracy of detection of metastatic disease （i.e. at least one metastatic lesion） was significantly higher for CEUS （91.2%） than for unenhanced sonography （81.4%） and was similar to that of triple-phase spiral CT （89.2 %）. In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients （94.4%）. CONCLUSION： CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.
基金Supported by the Bavarian Ministry of Economy (Leitprojekt Medizintechnik) and the Hans L(o|¨)wel Foundation, Bamberg,Germany
文摘AIM： To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation （RFA）. METHODS： Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma （HCC） underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma （IFNγ） secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index （SI）. To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay. RESULTS： Before RFA SI was 0.021 （±0.006） for CD4^＋ and 0.022 （± 0.004） for CD8^＋T cells against nonmalignant liver tissue and 0.018 （± 0.005） for CD4^＋ and 0.021 （± 0.004） for CD8^＋ cells against autologous tumor tissue. Four weeks after RFA SI against tumor tissue increased to 0.109 （± 0.005） for CD4＋ and 0.11 （± 0.012） for CD8＋ T cells against HCC, and to 0.115 （± 0.031） for CD4^＋ and 0.15 （± 0.02） for CD8^＋ cells for colorectal metastases （P 〈 0.0001）. No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respect（ve cancer cells was low with 2.62 （± 0.37） relative luminescence units （RLU）, but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was 〈 2% of maximum release in all experiments. CONCLUSION： Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8^＋ T cells after RFA.
基金This study was supported by the Medical Research Grants(#85300 and#85500)from the Shriners Hospitals for Children.The funding agency had no role in study data collection and analysis,data interpretation,or writing of the manuscript
文摘Background:Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing process.The molecular mechanisms driving keloid pathology remain incompletely understood,hindering development of targeted,effective therapies.Recent studies in our laboratory demonstrated that keloid keratinocytes exhibit adhesion abnormalities and display a transcriptional signature reminiscent of cells undergoing epithelial-mesenchymal transition(EMT),suggesting a role for EMT in keloid pathology.In the current study,we further define the EMT-like phenotype of keloid scars and investigate regulation of EMT-related genes in keloid.Methods:Primary keratinocytes from keloid scar and normal skin were cultured in the presence or absence of transforming growth factor beta 1(TGF-β1)+/-inhibitors of TGF-β1 and downstream signaling pathways.Gene expression was measured using quantitative polymerase chain reaction.Migration was analyzed using an in vitro wound healing assay.Proteins in keloid scar and normal skin sections were localized by immunohistochemistry.Statistical analyses utilized SigmaPlot(SyStat Software,San Jose,CA)or SAS?(SAS Institute,Cary,NC).Results:In keloid and normal keratinocytes,TGF-β1 regulated expression of EMT-related genes,including hyaluronan synthase 2,vimentin,cadherin-11,wingless-type MMTV integration site family,member 5A,frizzled 7,ADAM metallopeptidase domain 19,and interleukin-6.Inhibition of canonical TGF-β1 signaling in keloid keratinocytes significantly inhibited expression of these genes,and TGF-β1 stimulation of normal keratinocytes increased their expression.The inhibition of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway or the p38 mitogen-activated protein kinase pathway attenuated TGF-β1-induced expression of subsets of these genes.Migration of keloid keratinocytes,previously shown to be increased compared with normal keratinocytes,was significantly reduced by inhibition of TGF-β1 or ERK1/2 signaling.Biomarkers of EMT,includi
基金Supported by The 2007 SK Chemical Grant of the Korean Society of Gastroenterology
文摘AIM:To investigated the incidence of diversion colitis(DC) and impact of DC symptoms on quality of life(QoL) after ileostomy reversal in rectal cancer.METHODS:We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery,Korea University Anam Hospital.The participants totally underwent two rounds of the examinations.At first examination,endoscopies,tissue biopsies,and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations.At second examination,endoscopies,tissue biopsies,and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals.Clinicopathological data were based on the histopathological reports and clinical records of the patients.RESULTS:At the first examination,all of the patients presented with inflammation,which was mild in 15(50%) patients,moderate in 11(36.7%) and severe in 4(13.3%) by endoscopy and mild in 14(46.7%) and moderate in 16(53.3%) by histology.At the second examination,only 11(36.7%) and 17(56.7%) patients had mild inflammation by endoscopy and histology,respectively.There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination.The symptoms detected on the first and second questionnaires were mucous discharge in 12(40%) and 5(17%) patients,bloody discharge in 5(17%) and 3(10%) patients,abdominal pain in 4(13%) and 2(7%) patients and tenesmus in 9(30%) and 5(17%) patients,respectively.We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge,bleeding,abdominal pain and tenesmus in both time points.Diarrhea was detected in 9 patients at the second examination;this number correlated with the severity of DC(0%,0%,66.7%,33.3% vs 0%,71.4%,23.8%,4.8%,P = 0.001) and the symptom-related QoL(r =-0.791,P < 0.001).CONCLUSION:The severity of DC is relate
基金The German Research Foundation (DFG-Graduiertenkolleg 366) Grant Program for the High-Level Returned Scholars fromAbroad, Ministry of Personnel of China (No. 2004-2005)
文摘For phosphorus （P） recovery from wastewater, the effect of humic substances （HS） on the precipitation of calcium phosphate was studied. Batch experiments of calcium phosphate precipitation were undertaken with synthetic water that contained 20 mg/L phosphate （as P） and 20 mg/L HS （as dissolved organic carbon, DOC） at a constant pH value in the range of 8.0-10.0. The concentration variations of phosphate, calcium （Ca） and HS were measured in the precipitation process; the crystalline state and compositions of the precipitates were analysed by powder X-ray diffraction （XRD） and chemical methods, respectively. It showed that at solution pH 8.0, the precipitation rate and removal efficiency of phosphate were greatly reduced by HS, but at solution pH ≥9.0, the effect of HS was very small. The Ca consumption for the precipitation of phosphate increased when HS was added; HS was also removed from solution with the precipitation of calcium phosphate. At solution pH 8.0 and HS concentrations ≤3.5 mg/L, and at pH ≥ 9.0 and HS concentrations ≤ 10 mg/L, the final precipitates were proved to be hydroxyapatite （HAP） by XRD. The increases of solution pH value and initial Ca/P ratio helped reduce the influence of HS on the precipitation of phosphate.
基金German Science Foundation(DFG FOR 891/2,Du 404/3-2 to W.D.)is highly acknowledged.
文摘Aims Positive plant diversity-ecosystem function relations are ultimately driven by variation in functional traits among individuals that form a community.To date,research has largely focused on the role of species diversity for ecosystem functioning.However,substantial intraspecific trait variation is common and a significant part of this variation caused by genetic differences among individuals.Here,we studied the relative importance of species diversity and seed family(SF)diversity within species for growth and herbivory in experimental subtropical tree assemblages.Methods In 2010,we set up a field experiment in subtropical China,using four species from the local species pool.Trees were raised from seeds,with seeds from the same mother tree forming an SF.We established 23 plots containing one or four species(species diversity treatment)and one or four SFs per species(SF diversity treatment).Tree growth(stem diameter,plant height and crown expansion)and herbivory(percentage leaf loss due to leaf chewers)were monitored annually from 2011 to 2013.Important findings Tree species richness promoted growth but had no effect on herbivory.In contrast,SF diversity reduced growth and increased herbivory but only so in species mixtures.Most of the observed effects were time dependent,with the largest effect found in 2013.Our results suggest that biodiversity can affect plant performance directly via tree species-species interactions,or context dependent,via potential effects on inter-trophic interactions.Two important conclusions should be drawn from our findings.Firstly,in future studies regarding biodiversity and ecosystem functioning(BEF)relationships,intraspecific genetic diversity should be given similar weight as species diversity as it has often been neglected and its effects are not well understood.Secondly,we demonstrate opposite effects of biodiversity among and within species,stressing the importance to consider the effects of multiple levels of biodiversity simultaneously.
文摘AIM： To identify multi-detector computed tomography （MDCT） features most predictive of serous cystadenomas （SCAs）, correlating with histopathology, and to study the impact of cyst size and MDCT technique on reader performance. METHODS： The MDCT scans of 164 patients with surgically verified pancreatic cystic lesions were reviewed by two readers to study the predictive value of various morphological features for establishing a diagnosis of SCAs. Accuracy in lesion characterization and reader confidence were correlated with lesion size （≤3 cm or 〉≥3 cm） and scanning protocols （dedicated vs routine）. RESULTS： 28/164 cysts （mean size, 39 mm; range, 8-92 mm） were diagnosed as SCA on pathology. The MDCT features predictive of diagnosis of SCA were microcystic appearance （22/28, 78.6%）, surface Iobulations （25/28, 89.3%） and central scar （9/28, 32.4%）. Stepwise logistic regression analysis showed that only microcystic appearance was significant for CT diagnosis of SCA （P = 0.0001）. The sensitivity, specificity and PPV of central scar and of combined microcystic appearance and Iobulations were 32.4%/100%/100% and 68%/100%/100%, respectively. The reader confidence was higher for lesions 〉 3 cm （P = 0.02） and for MDCT scans performed using thin collimation （1.25-2.5 mm） compared to routine 5 mm collimation exams （P 〉 0.05）. CONCLUSION： Central scar on MDCT is diagnostic of SCA but is seen in only one third of SCAs. Microcystic morphology is the most significant CT feature in diagnosis of SCA. A combination of microcystic appearance and surface Iobulations offers accuracy comparable to central scar with higher sensitivity.
文摘Foreign bodies in the colon are encountered with increasing frequency, but only sporadic reports concerning their management have appeared in the literature. While most ingested foreign bodies usually pass through the gastrointestinal tract uneventfully, sharp foreign bodies such as toothpicks infrequently cause intestinal perforation and may even result in death. We report our experience with a patient with a sigmoid colon pseudodiverticulum formation, a complication of accidental ingestion of a toothpick that was diagnosed and successfully managed colonoscopically.
基金Supported by Bavarian Ministry of Health, Germany
文摘AIM： Pathological prion protein （PrP^sc） is responsible for the development of transmissible spongiform encephalopathies （TSE）. While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of priori precursor PrPc, which is constitutively expressed in the gastric mucosa.METHODS： We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting. The effect of central mediators of gastric inflammation, i.e., gastrin, prostaglandin E2 （PGE2）, tumor necrosis factor alpha （TNF-α） and interleukin 1 beta （IL-1β） on PrPc expression was analyzed in gastric cell lines.RESULTS： PrPc expression was increased in H pyloriinfection compared with non-infected controls and decreased to normal after successful eradication. Gastrin, PGE2, and IL-1β dose-dependently upregulated PrPc in gastric cells, while TNF-α had no effect.CONCLUSION： H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE2 and IL-1β synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.
基金the Alfried Krupp von Bohlen und Halbach Foundation,by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation)under Germany's Excellence Strategy via the Excellence Cluster 3D Matter Made to Order(EXC-2082/1-390761711)by the European Research Council(ERC Consolidator Grant TeraSHAPE,#773248)by the Karlsruhe School of Optics and Photonics(KSOP)。
文摘Early and efficient disease diagnosis with low-cost point-of-care devices is gaining importance for personalized medicine and public health protection.Within this context,waveguide-(WG)-based optical biosensors on the siliconnitride(Si_(3)N_(4))platform represent a particularly promising option,offering highly sensitive detection of indicative biomarkers in multiplexed sensor arrays operated by light in the visible-wavelength range.However,while passive Si_(3)N_(4)-based photonic circuits lend themselves to highly scalable mass production,the integration of low-cost light sources remains a challenge.In this paper,we demonstrate optical biosensors that combine Si_(3)N_(4)sensor circuits with hybrid on-chip organic lasers.These Si_(3)N_(4)-organic hybrid(SiNOH)lasers rely on a dye-doped cladding material that are deposited on top of a passive WG and that are optically pumped by an external light source.Fabrication of the devices is simple:The underlying Si_(3)N_(4)WGs are structured in a single lithography step,and the organic gain medium is subsequently applied by dispensing,spin-coating,or ink-jet printing processes.A highly parallel read-out of the optical sensor signals is accomplished with a simple camera.In our proof-of-concept experiment,we demonstrate the viability of the approach by detecting different concentrations of fibrinogen in phosphate-buffered saline solutions with a sensor-length(L-)-related sensitivity of S/L=0.16 rad nM^(-1)mm^(-1).To our knowledge,this is the first demonstration of an integrated optical circuit driven by a co-integrated low-cost organic light source.We expect that the versatility of the device concept,the simple operation principle,and the compatibility with cost-efficient mass production will make the concept a highly attractive option for applications in biophotonics and point-of-care diagnostics.
文摘MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.
基金Part of the research activities reported in this work were co-financed within European project HydroWEEE Demo “For Innovative Hydrometallurgical Processes To Recover Metals From WEEE Including Lamps And Batteries”:Demonstration(Grant agreement No.308549)
文摘This work presents an enhanced hydrometallurgical process for recycling lithium ion batteries. First, endof-life batteries were processed in a physical pre-treatment plant to obtain a representative electrode material. The resulting leachate was purified forth by iron-precipitation, liquid–liquid extractions, and an innovative Li–Na separation, in order to obtain valuable products. These products include high-grade graphite, cobalt oxide(Co3O4, purity 83%), cobalt oxalate(CoC2O4, purity 96%), nickel oxide(Ni O, purity89%), and lithium carbonate(Li2CO3, purity 99.8%). The recovery rate was quantitative for graphite, between 80% and 85% for cobalt depending on the nature of the recovery method, 90% for nickel, and 72%for lithium. Secondary streams were also valorized to obtain sodium sulfate(Na2SO4, purity 96%), and MnCoFe2O4 magnetic nano-sorbents according to the zero-waste concept. In order to close the loop, recycled Co3O4 and NiO were used as conversion-type anode materials for advanced lithium ion batteries showing promising performances.
文摘AIM: To investigate the prognostic significance of S100A4 expression in colorectal cancer and its correlation with expression of E-cadherin and p53. METHODS: A cohort of archival formalin-fixed paraff inembedded specimens was selected from 127 patients with colorectal cancer who underwent surgical resection between April 2000 and March 2004 at the Department of Surgery, Korea University Guro Hospital. The expression of protein S100A4 was evaluated according to the proportion of positively stained cancer cells. In each case, three core biopsies with a diameter of 2 mm were punched out and positioned in a recipient paraff in array block. Four-μm sections of these tissue array blocks were used for immunohistochemical analysis of protein S100A4, E-cadherin, and p53. Clinicopathological data were based on the original histopathologic reports and clinical records of patients. RESULTS: In normal colorectal mucosa, protein S100A4 immunoreactivity was clearly absent in both cytoplasm and nucleus. However, positive immunoreactivity of protein S100A4 was detected in 45 (35.4%) of the tumor cases. There was no significant association between positive immunoreactivity of protein S100A4 and clinicopathological parameters such as tumor differentiation or TNM stage, and also no correlation between the reactivity and E-cadherin or p53 expression. However, positive immunoreactivity of protein S100A4 was found to be associated with tumor recurrence (P = 0.004), and was also associated with significantly worse overall survival in the Kaplan-Meyer survival analysis (P = 0.044). After adjustment for tumor differentiation, tumor depth and nodal status, however, it failed to achieve statistical significance (P = 0.067). CONCLUSION: The expression of protein S100A4 is associated with tumor recurrence and poor overall survival in patients with colorectal cancer.
文摘Plants are a rich source of valuable secondary metabolites and in the recent years plant cell, tissue and organ cultures have been developed as an important alternative sources for the production of these compounds. Adventitious roots have been successfully induced in many plant species and cultured for the production of high value secondary metabolites of pharmaceutical, nutraceutical and industrial importance. Adoption of elicitation methods have shown improved synthesis of secondary metabolites in adventitious root cultures. Development of large-scale culture methods using bioreactors has opened up feasibilities of production of secondary metabolites at the industrial levels. In the present review we summarize the progress made in recent past in the area of adventitious root cultures for the production of secondary metabolites.
基金Feasibility grants from the Dutch government(MTVLA15144 and NITLS14050).
文摘Excessive release of neutrophil extracellular traps(NETs)is associated with disease severity and contributes to tissue injury,followed by severe organ damage.Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models,indicating that NETs are potential therapeutic targets.Here,we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody(tACPA)has broad therapeutic potential.Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology,including inflammatory arthritis(IA),pulmonary fibrosis,inflammatory bowel disease and sepsis.We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic intervention,whereas antibodies against other N-terminal post-translational histone modifications have no therapeutic effects.Because citrullinated histones are generated during NET release,we investigated the ability of tACPA to inhibit NET formation.tACPA suppressed NET release from human neutrophils triggered with physiologically relevant human disease-related stimuli.Moreover,tACPA diminished NET release and potentially initiated NET uptake by macrophages in vivo,which was associated with reduced tissue damage in the joints of a chronic arthritis mouse model of IA.To our knowledge,we are the first to describe an antibody with NET-inhibiting properties and thereby propose tACPA as a drug candidate for NET-mediated inflammatory diseases,as it eliminates the noxious triggers that lead to continued inflammation and tissue damage in a multidimensional manner.
文摘Complete mesocolic excision is a relatively new concept in western literature. It follows the same concept of total mesorectal excision and units’ routinely performing complete mesocolic excisions have good pathological results as well as good improvements in overall survival, disease free survival and local recurrence. And yet unlike total mesorectal excision, uptake in the West has been relatively slow with many units sceptical of the true benefits gained by taking up a more technically challenging and potentially more morbid procedure when there is a paucity of literature to support these claims. This article reviews complete mesocolic excision for colon cancer, attempting to identify the risks and benefits of the technique and particularly looking at the reasons why its uptake has not been universal. It also discusses the similarities of a complete mesocolic excision to a colon resection with a D3 lymphadenectomy as well as the role of a laparoscopic approach to this technique. Considering a D3 lymphadenectomy has been the standard of care for stage II and III colon cancers in many of our Asian neighbours for over 20 years, combining this data with data on complete mesocolic excision may provide enough evidence to support or refute the need for complete mesocolic excisions. Maybe there might be lessons to be learnt from our colleagues in the east.
文摘As a new class of two-dimensional materials, two-dimensional (2D) heterostructures constructed from metal chalcogenides (MCs) have been gaining tremendous attention due to their unprecedented physical and chemical phenomena, mainly originated from their distinct structural features such as composition, architecture type, spatial arrangement of each component, crystal structure, exposed facet and interface, dimensionality in their heterostructures. Towards the realization of practical applications, synthetic approaches need a rational design with a variety of architecture types including laterally-combined, vertically-aligned, and conformally-coated 2D MC heterostructures. Among various synthetic routes, solution-based synthesis is thought of as an alternative to fabrication through high-cost setups since it can control those structural features in a cheap fashion. This review presents recent progress on solution-based synthesis to produce various 2D MC heterostructures with a focus on the synthetic fundamentals in terms of thermodynamic and kinetic aspects related to the growth mechanism. Four different synthetic approaches are reviewed: seeded growth, cation exchange reaction, colloidal atomic layer deposition, direct synthesis including one-step process and modified electrochemical method. We also provide some representative applications of 2D MC heterostructures and their hybrid composites in various fields including optoelectronics, thermoelectrics, catalysis, and battery. Finally, we offer an insight into challenges and future directions in a synthetic improvement of 2D MC heterostructures.
