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Fiber Bragg grating-based Raman oscillators are capable of achieving targeted frequency conversion and brightness enhancement through the provision of gain via stimulated Raman scattering across a broad gain spectrum. This capability renders them an exemplary solution for the acquisition of high-brightness, specialized-wavelength lasers. Nonetheless, the output power of all-fiber Raman oscillators is typically limited to several hundred watts, primarily due to limitations in injectable pump power and the influence of higher-order Raman effects, which is inadequate for certain application demands. In this study, we introduce an innovative approach by employing a graded-index fiber with a core diameter of up to 150 μm as the Raman gain medium. This strategy not only enhances the injectable pump power but also mitigates higher-order Raman effects. Consequently, we have successfully attained an output power of 1780 W for the all-fiber Raman laser at 1130 nm, representing the highest output power in Raman fiber oscillators with any configuration reported to date.
The resistance to fenoxaprop-P-ethyl, a herbicide that inhibits acetyl-CoA carboxylase (ACCase), has emerged in shortawn foxtail (Alopecurus aequalis Sobol.) since the 1990s, presenting a considerable challenge to wheat (Triticum aestivum L.) production in China. One of the primary mechanisms responsible for this high-level resistance is the presence of mutations at codons 1781, 2041, and 2078 in the ACCase gene. However, the conventional methods used to detect these mutations, such as polymerase chain reaction (PCR) and gene sequencing, are time-consuming and labor-intensive. To address this issue and enable the prompt and effective detection of these common ACCase mutations in A. aequalis, a loop-mediated isothermal amplification (LAMP) strategy was developed. The LAMP assay specifically targets the Ile-1781-Leu and Asp-2078-Gly mutations within the ACCase gene of A. aequalis. Through the optimization of primers, systems, and conditions, the LAMP assay enables rapid differentiation between wild-type individuals and mutants of A. aequalis carrying either of these two mutations. Including SYBR Green I dye in the final reaction mixtures enables detection of the target mutation through a noticeable color change that can be observed with the naked eye. It is noteworthy that the sensitivity of the LAMP assay was approximately 104-fold greater than that of conventional PCR methods. Additionally, a derived cleaved amplified polymorphic sequence (dCAPS) assay was established for each mutation to distinguish between homozygous and heterozygous mutants. Overall, the developed LAMP assay could efficiently detect the Ile-1781-Leu and Asp-2078-Gly mutations in the ACCase gene of A. aequalis, offering significant advantages for the monitoring and management of fenoxaprop-P-ethyl resistance.
OBJECTIVES/GOALS: Incomplete mucosal healingand dysbiosis prevent long-term remission after colitis. IL4 may restore colon homeostasis through its action on immune cells and the microbiome. We will demonstrate this mechanism using genetically modified mice and molecular tools. This may result in target therapies that prolong remission in patients with IBD. METHODS/STUDY POPULATION: Mice were treated with 3% dextran sulfate sodium (DSS) in drinking water for 5 days to induce colitis. Mice were monitored daily for changes in body weight, and to monitor colitis severity. At each endpoint, mice were sacrificed and colon length was measured. For disease severity assessment, mouse colons were prepared in paraffin sections by the 'swiss-rolling' method. For flow cytometry, lamina propria mononuclear cell isolation was performed and cellular populations were stained with fluorophore-conjugated antibodies. IL4-eGFP-expressing (4get) mice were used to analyze the cellular expression of IL4 after colitis. Cell-specific IL4 deletion mice were generated using the cre-lox system. RESULTS/ANTICIPATED RESULTS: IL4-deficient mice had worse colitis compared with wild-type controls. Flow cytometry of lamina propria cells from 4get mice showed that most IL4-producing cells after colitis are eosinophils (CD11b+SiglecF+). Flow cytometry of C57bl6 mice showed an influx of IL4Ra+ monocytes (CD11b+Ly6C+) and macrophages (CD11b+F480+). IL4-stimulated bone marrow-derived macrophages demonstrated an increase in HB-EGF mRNA transcription. Myeloid-specific IL4R deleted mice had no difference in colitis severity compared with controls. Neutrophil-specific IL4R-deleted mice had increased colitis severity and mortality. Co-housing of littermate mice rescued recovery after DSS in IL4 deficient mice. DISCUSSION/SIGNIFICANCE: IL4 appears to play a role in restoring homeostasis after colitis. The mechanism depends on eosinophil-derived IL4, and action through neutrophils. However, the reparative function of IL4 can be shared with deficient mice through the microbiome. I will study the cellular and microbial mechanism by which IL4 restores homeostasis after colitis.
Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
Shortawn foxtail (Alopecurus aequalis Sobol.) is an obligate wetland plant that is widely distributed throughout Europe, temperate Asia, and North America. In China, it is widespread in the middle and lower reaches of the Yangtze River as a noxious weed in winter cropping fields with a rice (Oryza sativa L.) rotation. The acetolactate synthase (ALS)-inhibiting herbicide mesosulfuron-methyl has been widely used to control annual grass and broadleaf weeds, including A. aequalis, in wheat (Triticum aestivum L.) fields, leading to the selection of herbicide-resistant weeds. In this study, an A. aequalis population, AHFT-4, that survived mesosulfuron-methyl at the field-recommended rate (9 g ai ha−1) was collected in Anhui Province. Single-dose testing confirmed that the suspected resistant AHFT-4 had evolved resistance to mesosulfuron-methyl. Target gene sequencing revealed a resistance mutation of Pro-197-Ala in ALS1 of the resistant plants, and a derived cleaved amplified polymorphic sequence marker was developed to specifically detect the mutation. A relative expression assay showed no significant difference in ALS expression between AHFT-4 and a susceptible population without or with mesosulfuron-methyl treatment. Whole-plant dose–response bioassays indicated that AHFT-4 had evolved broad-spectrum cross-resistance to ALS-inhibiting herbicides of all five chemical families tested, with GR50 resistance index (RI) values ranging from 21 to 206. However, it remained susceptible to the photosystem II inhibitor isoproturon. Pretreatment with the cytochrome P450 inhibitor malathion or the glutathione S-transferase inhibitor 4-chloro-7-nitrobenzoxadiazole had no significant effects on the resistance of AHFT-4 to mesosulfuron-methyl. To our knowledge, this study reports for the first time the ALS gene Pro-197-Ala substitution conferring broad-spectrum cross-resistance to ALS-inhibiting herbicides in A. aequalis.
Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) is a multidrug-resistant gram-negative bacteria (MDR-GNB) that is rapidly emerging as a life-threatening nosocomial disease in many countries. We sought to identify the risk factors associated with mortality for carriage of CRE in patients at a tertiary-care teaching hospital. Methods: A retrospective observational study was conducted between January 2020 to December 2021 in a tertiary-care teaching healthcare facility, University Malaya Medical Centre in Malaysia. The study included all inpatients aged ≥18 years who had a CRE infection or were colonized during the study period. The genotype was identified by polymerase chain reaction (PCR). Statistical analysis of data including a multivariate logistic regression analysis was conducted using SPSS version 23.0 software. Results: In total, 176 cases of CRE (130 infection and 46 colonized) were identified, and the mortality rate was 31.8%. The main sources of CRE were rectal swab (61.9%), blood (11.9%), and respiratory sources (11.9%). Klebsiella pneumoniae (55.7%) was the predominant species, followed by Escherichia coli (21.6%). Among the isolates, 17.7% were non–CPE-CRE and 82.3% were CPE-CRE: NDM (69.3%) and OXA (10.8%). In multivariate analysis, the factors associated with mortality were older age (OR, 1.040; 95% CI, 1.012–1.069), longer length of stay (OR, 0.974; 95% CI, 0.955–0.994), use of central venous catheter (OR, 0.287; 95% CI, 0.094–0.878), and arterial lines (OR, 0.292; 95% CI, 0.095–0.891). Conclusion: Patients with CRE had a high mortality rate. Older age, longer duration of stay, indwelling CVC and arterial line were independent risk factors for death. Infection prevention and control measures to reduce CRE, such as active surveillance, contact precautions, compliance to intravenous catheter care bundles, healthcare worker education, and hand hygiene adherence, should be implemented.
Objectives: Surgical-site infections (SSIs) cause significant increases in mortality, morbidity, and prolonged hospitalization after cesarean deliveries. We assessed the effectiveness of the implementation of an SSI bundle in reducing postoperative infections in cesarean deliveries in a tertiary-care teaching hospital in Malaysia. Method: We conducted a quality-improvement study on all women who underwent labor and scheduled cesarean sections at the University Malaya Medical Center (UMMC) between May and December 2020. The preintervention period was May–June 2020 and the postintervention period was September–December 2020. Patients were followed for 90 days after their operation. Before the intervention, SSI rates and compliance with prevention practices were documented. A multidisciplinary team was formed, and education regarding the elements of the SSI prevention bundle was conducted before they were implemented. The care bundle focused on monitoring compliance with preoperative bathing, contact time for skin preparation, hair management, and antibiotics prophylaxis given within 60 minutes prior to incision, as well as patient education. Result: With the implementation of the SSI bundle, we observed a significant reduction in the SSI rate by 50%, from 7 per 100 procedures to 2 per 100 procedures. Compared with the preintervention period, overall compliance with bundle elements improved greatly for preoperative bathing (0 vs 95.7%) and contact time for skin preparation (0 vs 98.8%). In the postintervention period, the method of hair removal was documented, compared to no documentation during the preintervention period. The administration of prophylactic antibiotics within 60 minutes prior incision decreased from 99% to 92.3%. Conclusion: Implementation of an SSI prevention bundle successfully reduced the rate of SSI after cesarean section. The SSI prevention bundle together with improvements by multidisciplinary teams and a good patient-safety culture helped reduce SSI rates. Patient education on pre- and postoperative infection prevention also played an important role in reducing this infection rate.
We examined whether physical activity (PA) explains the association between dietary inflammatory potential and osteoarthritis (OA) in the elderly. A total of 1249 elderly people (≥65 years) were eligible for this study from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. The semi-quantitative Food Frequency Questionnaire (FFQ) and Global PA Questionnaire (GPAQ) were used to evaluate the diet and PA of the elderly, respectively. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence interval (CI) between Energy-adjusted Dietary Inflammatory Index (E-DII) and OA. The interaction of E-DII and PA on depressive events was tested, and the mediation analysis of PA was performed. The average E-DII in this study was +0.68 (SE 0.08), and the score ranges from -5.32 (most anti-inflammatory) to +4.26 (most pro-inflammatory). In comparison with the first quartile, the elderly from the second quartile (OR: 1.16 [95% CI: 1.06, 1.68]) to the fourth quartile (OR: 1.64 [95% CI: 1.13, 2.37]) had a higher risk of OA before adjustment for PA. An interaction was observed between E-DII and PA in terms of the risk of OA (PInteraction < 0.001). The whole related part was mediated by PA (20.08%). Our findings indicated that the higher pro-inflammatory potential of diet was associated with a higher risk of OA, and low PA was an important part of the mediating factor in the relationship between systemic low-grade dietary inflammation and the risk of OA.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
We aimed to examine whether baseline neutrophil counts affected the risk of new-onset proteinuria in hypertensive patients, and, if so, whether folic acid treatment is particularly effective in proteinuria prevention in such a setting. A total of 8208 eligible participants without proteinuria at baseline were analysed from the renal substudy of the China Stroke Primary Prevention Trial. Participants were randomised to receive a double-blind daily treatment of 10 mg of enalapril and 0·8 mg of folic acid (n 4101) or 10 mg of enalapril only (n 4107). The primary outcome was new-onset proteinuria, defined as a urine dipstick reading of ≥1+ at the exit visit. The mean age of the participants was 59·5 (sd, 7·4) years, 3088 (37·6 %) of the participants were male. The median treatment duration was 4·4 years. In the enalapril-only group, a significantly higher risk of new-onset proteinuria was found among participants with higher neutrophil counts (quintile 5; ≥4·8 × 109/l, OR 1·44; 95 % CI 1·00, 2·06), compared with those in quintiles 1–4. For those with enalapril and folic acid treatment, compared with the enalapril-only group, the new-onset proteinuria risk was reduced from 5·2 to 2·8 % (OR 0·49; 95 % CI 0·29, 0·82) among participants with higher neutrophil counts (≥4·8 × 109/l), whereas there was no significant effect among those with neutrophil counts <4·8 × 109/l. In summary, among hypertensive patients, those with higher neutrophil counts had increased risk of new-onset proteinuria, and this risk was reduced by 51 % with folic acid treatment.
In this research communication we describe the DGAT1 sequence and promoter region in dairy cows and buffalo and compare the activities of DGAT1 between the two species in order to increase knowledge of the cause of milk fat variation. pGL-3 basic vectors were used to construct the reporter gene. Based on the predicted promoter region, 4 truncated plasmid vectors were constructed in cow-DGAT1 and 3 plasmid vectors in buffalo-DGAT1. Each reporter plasmid was transfected into the bovine mammary epithelial cell (BMEC), 293T cell, and CHO cells to analyze the activity using Dual-Luciferase Reporter Assay System. The results show that the region between −93 to −556 bp was essential for cow promoter activity while −84 to −590 bp was essential for buffalo promoter activity revealing these regions contain core promoter. The buffalo has higher promoter activity than cow yet it was not statistically significant. Comparison of candidate mutation K232A between cow and buffalo population revealed the presence of both the allelic population in dairy cows (lysine and alanine) however, only K (lysine) allelic amino acid was found in buffalo population. The absence of the alanine allelic population from buffalo explains the higher fat content of buffalo milk.
The Chinese National Twin Registry (CNTR), initiated in 2001, has now become the largest twin registry in Asia. From 2015 to 2018, the CNTR continued to receive Chinese government funding and had recruited 61,566 twin-pairs by 2019 to study twins discordant for specific exposures such as environmental factors, and twins discordant for disease outcomes or measures of morbidity. Omic data, including genetics, genomics, metabolomics, and proteomics, and gut microbiome will be tested. The integration of omics and digital technologies in public health will advance our understanding of precision public health. This review introduces the updates of the CNTR, including study design, sample size, biobank, zygosity assessment, advances in research and future systems epidemiologic research.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
Methods
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
Results
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
Conclusions
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
Little is known about the joint mental health effects of air pollution and tobacco smoking in low- and middle-income countries.
Aims
To investigate the effects of exposure to ambient fine particulate matter pollution (PM2.5) and smoking and their combined (interactive) effects on depression.
Method
Multilevel logistic regression analysis of baseline data of a prospective cohort study (n=41785). The 3-year average concentrations of PM2.5 were estimated using US National Aeronautics and Space Administration satellite data, and depression was diagnosed using a standardised questionnaire. Three-level logistic regression models were applied to examine the associations with depression.
Results
The odds ratio (OR) for depression was 1.09 (95% CI 1.01–1.17) per 10 μg/m3 increase in ambient PM2.5, and the association remained after adjusting for potential confounding factors (adjusted OR = 1.10, 95% CI 1.02–1.19). Tobacco smoking (smoking status, frequency, duration and amount) was also significantly associated with depression. There appeared to be a synergistic interaction between ambient PM2.5 and smoking on depression in the additive model, but the interaction was not statistically significant in the multiplicative model.
Conclusions
Our study suggests that exposure to ambient PM2.5 may increase the risk of depression, and smoking may enhance this effect.
Leucine plays an important role in promoting muscle protein synthesis and muscle remodelling. However, what percentage of leucine is appropriate in creep feed and what proteome profile alterations are caused by dietary leucine in the skeletal muscle of piglets remain elusive. In this case, we applied isobaric tags for relative and absolute quantitation to analyse the proteome profile of the longissimus dorsi muscles of weanling piglets fed a normal leucine diet (NL; 1·66 % leucine) and a high-leucine diet (HL; 2·1 % leucine). We identified 157 differentially expressed proteins between these two groups. Bioinformatics analysis of these proteins exhibited the suppression of oxidative phosphorylation and fatty acid β-oxidation, as well as the activation of glycolysis, in the HL group. For further confirmation, we identified that SDHB, ATP5F1, ACADM and HADHB were significantly down-regulated (P<0·01, except ATP5F1, P<0·05), whereas the glycolytic enzyme pyruvate kinase was significantly up-regulated (P<0·05) in the HL group. We also show that enhanced muscle protein synthesis and the transition from slow-to-fast fibres are altered by leucine. Together, these results indicate that leucine may alter energy metabolism and promote slow-to-fast transitions in the skeletal muscle of weanling piglets.
The effect of nitrogen gas addition in Ar-based double-layer shielding gas on the impact toughness of welded ultra-ferritic stainless steel during an autogenous gas tungsten arc welding (GTAW) process was investigated. The nitrogen behavior was proposed. The microstructure, mechanical properties, and fracture surface morphology of the weld metals have been evaluated. More equiaxed crystals, refined grain, narrow HAZ width, and increased microhardness were produced with nitrogen addition. Experimental findings indicated that nitrogen diffused into HAZ and dissolved into weld pool. The solute distribution was changed thus bringing significant constitutional supercooling and decreased temperature gradient of weld pool, which contributed to fine microstructure. Impact toughness at room temperature was enhanced from 2J to 9J (welds), 5J–13J (HAZ). Ductile fracture zone was produced about 0.3–0.5 mm thickness distance from the weld surface. A significant increased impact toughness of weld metal was due to the refinement of microstructure and element addition.
Carbon nanodots (CDs) have generated enormous excitement because of their superiority in water solubility, chemical inertness, low toxicity, ease of functionalization and resistance to photobleaching. Here we report a facile thermal pyrolysis route to prepare CDs with high quantum yield (QY) using citric acid as the carbon source and ethylene diamine derivatives (EDAs) including triethylenetetramine (TETA), tetraethylenepentamine (TEPA) and polyene polyamine (PEPA) as the passivation agents. We find that the CDs prepared from EDAs, such as TETA, TEPA and PEPA, show relatively high photoluminescence (PL) QY (11.4, 10.6, and 9.8%, respectively) at λex of 465 nm. The cytotoxicity of the CDs has been investigated through in vitro and in vivo bio-imaging studies. The results indicate that these CDs possess low toxicity and good biocompatibility. The unique properties such as the high PL QY at large excitation wave length and the low toxicity of the resulting CDs make them promising fluorescent nanoprobes for applications in optical bio-imaging and biosensing.
The purpose of the present study was to evaluate the impact of a lifestyle intervention programme, combined with a daily low-glycaemic index meal replacement, on body-weight and glycaemic control in subjects with impaired glucose regulation (IGR). Subjects with IGR were randomly assigned to an intervention group (n 46) and a control group (n 42). Both groups received health counselling at baseline. The intervention group also received a daily meal replacement and intensive lifestyle intervention to promote healthy eating habits during the first 3 months of the study, and follow-up visits performed monthly until the end of the 1-year study. Outcome measurements included changes in plasma glucose, glycated Hb (HbA1c), plasma lipids, body weight, blood pressure and body composition (such as body fat mass and visceral fat area). The results showed that body-weight loss after 1 year was significant in the intervention group compared with the control group ( − 1·8 (sem 0·35) v.− 0·6 (sem 0·40) 2·5 kg, P< 0·05). The 2 h plasma glucose concentration decreased 1·24 mmol/l in the intervention group and increased 0·85 mmol/l in the control group (P< 0·05) compared with their baseline, respectively. A 5 kg body-weight loss at 1 year was associated with a decrease of 1·49 mmol/l in 2 h plasma glucose (P< 0·01). The incidence of normal glucose regulation (NGR) in the two groups was significantly different (P= 0·001). In conclusion, the combination of regular contact, lifestyle advice and meal replacement is beneficial in promoting IGR to NGR.
Boron-doped, single (∼54 nm) or double (∼21 + 54 nm) Si1−xGex layers were epitaxially grown on 300-mm-diameter p−-Si(100) device wafers with 20 nm technology node design features, by ultrahigh vacuum chemical vapor deposition. The Si1−xGex/Si wafers were annealed in the temperature range of 950–1050 °C for 60 s to investigate the effect of annealing on possible changes of Ge content and Si stress near the Si1−xGex/Si interface. High spectral resolution, micro-Raman spectroscopy was used as a nondestructive characterization technique with five excitation wavelengths of 363.8, 441.6, 457.9, 488.0, and 514.5 nm. Ge diffusion and generation of compressive stress at the Si1−xGex/Si interface were measured on all annealed wafers. Ge diffusion and the accumulation of compressive Si stress after annealing showed significantly different behaviors between single- and double-layer Si1−xGex/Si wafers. Raman characterization results were compared with secondary ion mass spectroscopy and high-resolution x-ray diffraction results.