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Perspective on this Article from An Expanded Risk Prediction Model for Lung Cancer

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Background: Tobacco-induced lung cancer is characterized by a deregulated inflammatory microenvironment. Variants in multiple genes in inflammation pathways may contribute to risk of lung cancer.Methods: We therefore conducted a three-stage comprehensive pathway analysis (discovery, replication, and meta-analysis) of inflammation gene variants in ever-smoking lung cancer cases and controls. A discovery set (1,096 cases and 727 controls) and an independent and nonoverlapping internal replication set (1,154 cases and 1,137 controls) were derived from an ongoing case–control study. For discovery, we used an iSelect BeadChip to interrogate a comprehensive panel of 11,737 inflammation pathway single-nucleotide polymorphisms (SNP) and selected nominally significant (P < 0.05) SNPs for internal replication.Results: There were six SNPs that achieved statistical significance (P < 0.05) in the internal replication data set with concordant risk estimates for former smokers and five concordant and replicated SNPs in current smokers. Replicated hits were further tested in a subsequent meta-analysis using external data derived from two published genome-wide association studies (GWAS) and a case–control study. Two of these variants (a BCL2L14 SNP in former smokers and an SNP in IL2RB in current smokers) were further validated. In risk score analyses, there was a 26% increase in risk with each additional adverse allele when we combined the genotyped SNP and the most significant imputed SNP in IL2RB in current smokers and a 36% similar increase in risk for former smokers associated with genotyped and imputed BCL2L14 SNPs.Conclusions/Impact: Before they can be applied for risk prediction efforts, these SNPs should be subject to further external replication and more extensive fine mapping studies. Cancer Epidemiol Biomarkers Prev; 21(7); 1213–21. ©2012 AACR.

Background: Established psychosocial risk factors increase the risk for experimentation among Mexican origin youth. Now, we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation.Methods: Participants (N = 1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, TX, provided prospective data on cigarette experimentation over 3 years. Psychosocial data were elicited twice—baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin, and opioid pathways.Results: After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 [95% confidence interval (CI), 1.62–3.13] times more likely to have experimented since baseline than participants with five or fewer. Among committed never-smokers (N = 872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N = 246), older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation.Conclusions: Our findings, which have implications for development of culturally specific interventions, need to be validated in other ethnic groups.Impact: These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger than committed never-smokers. Cancer Epidemiol Biomarkers Prev; 21(1); 228–38. ©2011 AACR.

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Mechanical thrombectomy is not only effective for managing patients with acute ischemic stroke (AIS), but it also enables a valuable histological analysis of thrombi. Previous studies indicated that regulatory T cells (Treg) adoptive transfer might alleviate the hemorrhagic transformation. However, whether Treg in intracranial thrombi correlates with hemorrhagic transformation after mechanical thrombectomy remains unclear. This study mainly analyzed the colocation of Treg markers in serial thrombus sections stained serially for CD4 and CD25 in groups of hemorrhagic or nonhemorrhagic transformation. Second, to investigate whether these immunohistochemical parameters could provide any additional information beyond hemorrhagic transformation, we compared the overlap between Treg markers among other groups, such as functional outcomes, stroke subtypes, and gender. Our results showed that the number of CD4+CD25+ Treg cells was lower in the hemorrhagic transformation thrombi than in the nonhemorrhagic group ( p < 0.001 ) but there were no significant differences otherwise. The present finding of CD4+CD25+ Treg cell reductions in thrombi associated with hemorrhagic transformation provides the histological evidence supporting that thromboinflammation might involve in the pathological process of an acute stroke after mechanical thrombectomy.

An easy scoring system to predict the risk of poor outcome after mechanical thrombectomy among the elderly is currently not available. Therefore, we aimed to develop a nomogram for predicting the probability of negative prognosis in aged patients with acute ischemic stroke undergoing thrombectomy. In addition, we sought to investigate the association between histological thrombus composition and stroke characteristics. To this end, we prospectively studied a developed cohort using data collected from a stroke center from November 2015 to December 2019. The main outcome was functional independence, defined as a modified Rankin Scale score ≤ 2 at 90 days following a mechanical thrombectomy. A nomogram model based on multivariate logistic models was generated. The retrieved thrombi were stained with hematoxylin and eosin and assessed according to histological composition. Our results demonstrated that age ≥ 72 years was independently associated with poor outcome. A total of 304 participants completed the follow-up data to generate the nomogram model. After multivariate logistic regression, five variables remained independent predictors of outcome, including older age, hemorrhagic transformation, thrombolysis in cerebral infarction score, National Institute of Health Stroke score, and neutrophil-to-lymphocyte ratio, and were used to generate the nomogram. The area under the receiver-operating characteristic curve of the model was 0.803. The clots from elderly subjects with large-artery atherosclerosis, anterior circulation, and successful recanalization groups had a higher percentage of fibrin compared to those of younger patients. This is the first nomogram to be developed and validated in a stroke center cohort for individualized prediction of poor outcome in elderly patients after mechanical thrombectomy. Clot composition provides valuable information on the underlying pathogenesis of oxidation in older patients.

Yarlung Zangbo Grand Canyon National Nature Reserve has the most complete vertical vegetation belts in China. However, identification and distribution of vertical vegetation belts is still uncertain and in debate. To explore the above issues, 190 plots were surveyed within the reserve from 2019 to 2021. Based on the vegetation plot data, cluster analysis, ordination analysis, and biodiversity statistics were performed to reveal the structure of vertical vegetation belts–the driving factors of vegetation distribution–to describe the main biodiversity patterns. Five vertical vegetation belts were identified by clustering. NMDS ordination showed that the main factor of vegetation distribution is elevation. Based on the results of the analysis and previous literature, a new scheme of vertical vegetation belts in the south slope of the reserve was proposed. There was a lower montane seasonal rainforest belt (600–1100 m), a lower montane evergreen broadleaf forest belt (1100–1800 m), a middle montane semi-evergreen broadleaf forest belt (1800–2400 m), a subalpine evergreen needleleaf forest belt (2400–3800 m), a alpine shrubland and meadow belt (3800–4400 m), an alpine sparse vegetation belt (4400–4800 m), and a nival belt (4800–7782 m). Among them, the seasonal rainforest belts are the northernmost distribution of this type, and the semi-evergreen broadleaf forest belts exist only in the Eastern Himalayas. The study showed a unimodal pattern in plant species diversity, the peak of which is about 1900 m. The middle montane semi-evergreen broadleaf forest belt had the highest species diversity in the reserve. This study settled the issues regarding the vertical vegetation belts, the main drivers of vegetation and assessment of plant species diversity in the south slope of the Yarlung Zangbo Grand Canyon National Nature Reserve. It provides essential support for the management and conservation of these ecosystems in the reserve.

Background: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. Methods: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. Results: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. Conclusion: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

Transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) is currently considered a novel therapeutic strategy for diabetic nephropathy (DN). However, the mechanisms by which UC-MSCs ameliorate renal fibrosis in DN are not well understood. Herein, we firstly investigated the therapeutic effects of mouse UC-MSC infusion on kidney structural and functional impairment in streptozotocin- (STZ-) induced diabetic mice. We found that the repeated injection with mUC-MSCs alleviates albuminuria, glomerulus injury, and fibrosis in DN mouse models. Next, mesangial cells were exposed to 5.6 mM glucose, 30 mM glucose, or mUC-MSC-conditioned medium, and then we performed western blotting, immunofluorescence, wound healing assay, and cell proliferation assay to measure extracellular matrix (ECM) proteins and matrix metalloproteinases (MMPs), myofibroblast transdifferentiation (MFT), and cell proliferation. We demonstrated that mUC-MSC paracrine decreased the deposition of fibronectin and collagen I by inhibiting TGF-β1-triggered MFT and cell proliferation mediated by PI3K/Akt and MAPK signaling pathways, and elevating the levels of MMP2 and MMP9. Importantly, we provided evidence that the antifibrosis role of mUC-MSC paracrine in DN might be determined by exosomes shed by MSCs. Together, these findings reveal the mechanisms underlying the therapeutic effects of UC-MSCs on renal fibrosis in DN and provide the evidence for DN cell-free therapy based on UC-MSCs in the future.

Solanum betacea is a sub-tropical tree, and the fruit has high nutritional value, unique flavor and color. It is used as a functional ingredient in health care, food, cosmetic and pharmaceutical applications. The complete chloroplast(Cp) genome of S. betacea has been assembled and annotated in this paper. Its length was 155,937 bp, containing a large single-copy region of 86,731 bp, a small single-copy region of 18,450 bp, and a pair of IR regions of 25,378 bp in each. The complete chloroplast genome of S. betacea contained 134 genes, including 90 protein-coding genes, 36 transfer RNA genes (tRNAs), and 8 ribosome RNA genes (rRNAs). The overall GC content was 37.7% and the GC contents of the LSC, SSC, and IR regions were 35.7%, 31.8%, and 43.1%, respectively. Phylogenetic analysis with the reported chloroplast genomes revealed that S. betacea has been most closely related to Solanum torvum. These findings will provide useful information for further investigation of chloroplast genome evolution in Solanum betacea.

Background: Cognitive impairment can occur after aneurysmal subarachnoid hemorrhage (aSAH) though it commonly tends to be neglected. Red blood cell (RBC) indices are associated with long-term functional outcomes, while it is unclear whether RBC indices could be a potential predictor of cognitive decline after aSAH. We aimed to investigate the association between RBC indices and post-aSAH cognitive impairment at 1 year. Methods: Patients with aSAH received neuropsychological test by the Montreal Cognitive Assessment (MoCA) and underwent serum and cerebrospinal fluid (CSF) samples test. To determine the association between RBC indices and cognitive impairment after acute aSAH, we adjusted for demographic and vascular risk factors using multivariate logistic regression analysis. Results: Of the 126 patients included in this study, 33% (42/126) of them were diagnosed with cognitive impairment (MoCA Conclusion: In this aSAH population, our data shows the positive association between MCH and MCV and cognitive impairment at 1 year.

Mechanical thrombectomy (MT) is effective in managing patients with acute ischemic stroke (AIS) caused by large-vessel occlusions and allows for valuable histological analysis of thrombi. However, whether bridging therapy (pretreatment with intravenous thrombolysis before MT) provides additional benefits in patients with middle cerebral artery (MCA) occlusion remains unclear. Therefore, this study aimed to compare the effects of direct MT and bridging therapy, and to elucidate the correlation between thrombus composition and stroke subtypes. Seventy-three patients with acute ischemic stroke who received MT, were eligible for intravenous thrombolysis, and had MCA occlusion were included. We matched 21 direct MT patients with 21 bridging therapy patients using propensity score matching and compared their 3rd-month clinical outcomes. All MCA thrombi (n = 45) were histologically analyzed, and the red blood cell (RBC) and fibrin percentages were quantified. We compared the clot composition according to stroke etiology (large-artery atherosclerosis and cardioembolism) and intravenous thrombolysis application. The baseline characteristics showed no difference between groups except for a higher atrial fibrillation rate and NIHSS score on admission in the direct MT group. We performed a supportive analysis using propensity score matching but could not find any differences in the functional outcome, mortality, and intracerebral hemorrhage. In the histological clot analysis, the cardioembolic clots without intravenous thrombolysis pretreatment had higher RBC (P = 0.042) and lower fibrin (P = 0.042) percentages than the large-artery atherosclerosis thrombi. Similar findings were observed in the thrombi treated with recombinant tissue plasminogen activator (P = 0.012). In conclusion, there was no difference in the functional outcomes between the direct MT and bridging therapy groups. However, randomized trials are needed to elucidate the high ratio of cardioembolism subtype in our group of patients. The histological MCA thrombus composition differed between cardioembolism and large-artery atherosclerosis, and this finding provides valuable information on the underlying pathogenesis and thrombus origin.

An easily scoring system to predict the risk of cognitive impairment after minor ischemic stroke has not been available. We aimed to develop and externally validate a nomogram for predicting the probability of post-stroke cognitive impairment (PSCI) among hospitalized population with minor stroke. Moreover, the association of Trimethylamine N-oxide (TMAO) with PSCI is also investigated. We prospectively conducted a developed cohort on collected data in stroke center from June 2017 to February 2018, as well as an external validation cohort between June 2018 and February 2019. The main outcome is cognitive impairment defined as p ≤ 0.001). In conclusion, this scoring system is the first nomogram developed and validated in a stroke center cohort for individualized prediction of cognitive impairment after minor stroke. Higher plasma TMAO level at admission suggests a potential marker of PSCI.

BACKGROUND: Studies across racial/ethnic groups indicate that physical activity (PA) and alcohol consumption are positively associated, and that alcohol consumption is negatively associated with body mass index (BMI), but this relationship is less often evaluated in Hispanics. The purpose of this study was to assess the relationships between alcohol consumption, PA, and BMI in Hispanic adults. METHODS: In this secondary data analysis of a Mexican-American cohort, we collected self-reported PA, alcohol consumption, and demographics, and measured height and weight. Linear regression assessed the association between PA and alcohol consumption with BMI, controlling for covariates. Total sample for analyses was n = 3897. RESULTS: We found an inverse relationship between high PA and BMI in the full sample (adjusted estimate = − 0.03, 95% CI − 0.07, − 0.01) and in females, but not males. We also found an inverse relationship between current alcohol use and BMI in the full sample (adjusted estimate = − 0.05, 95% CI − 0.09, − 0.01) and both sexes. There was no significant interaction between PA and alcohol use on BMI. CONCLUSIONS: In this study of Mexican-origin adults, current alcohol use and high PA were associated with lower BMIs, but there was no interaction between PA and alcohol use. These results can be used to inform multiple behavior change interventions in Mexican-origin adults.

Mechanical thrombectomy is not only effective for managing patients with acute ischemic stroke (AIS), but it also enables a valuable histological analysis of thrombi. Previous studies indicated that regulatory T cells (Treg) adoptive transfer might alleviate the hemorrhagic transformation. However, whether Treg in intracranial thrombi correlates with hemorrhagic transformation after mechanical thrombectomy remains unclear. This study mainly analyzed the colocation of Treg markers in serial thrombus sections stained serially for CD4 and CD25 in groups of hemorrhagic or nonhemorrhagic transformation. Second, to investigate whether these immunohistochemical parameters could provide any additional information beyond hemorrhagic transformation, we compared the overlap between Treg markers among other groups, such as functional outcomes, stroke subtypes, and gender. Our results showed that the number of CD4+CD25+ Treg cells was lower in the hemorrhagic transformation thrombi than in the nonhemorrhagic group (p < 0.001) but there were no significant differences otherwise. The present finding of CD4+CD25+ Treg cell reductions in thrombi associated with hemorrhagic transformation provides the histological evidence supporting that thromboinflammation might involve in the pathological process of an acute stroke after mechanical thrombectomy.

The primary aim of the study was to estimate the effect of sleep duration on prospective type 2 diabetes (T2D) risk across demographic characteristics and follow-up periods, and test BMI as a mediator and moderator. Data included adults (M(age) = 39.0 ± 12.7y) born in the US or Mexico recruited from 2001-2012 in a Mexican American cohort study conducted in Houston, Texas (n=15,779). Participants completed self-reported questionnaires at baseline related to health, health behaviors (sleep duration, physical activity, smoking, drinking) and sociocultural factors, and were followed up annually. Cox proportional hazard models estimated hazard ratios (HR) for the effect of sleep duration on T2D diagnosis at follow-up. Of the participants, 10.3% were diagnosed with T2D. Self-reported ≤5 hours of sleep, compared to 7-8 hours, at baseline predicted greater risk for T2D (HR=1.32, p=.001), yet was no longer significant after adjusting for sociodemographic characteristics and BMI. Notably, those with BMI < 25 kg/m(2) reporting ≤5 hours of sleep were at significant risk for T2D at 3 (HR=4.13, p=.024) and 5 year follow-up (HR=3.73, p=.008) compared to 7-8 hours. Obesity status accounted for 31.6% and 27.3% of the variance in the association between ≤5 and 6 hours of sleep and increased T2D risk, respectively. Results highlighted the mediating and moderating role of BMI, and its effect on T2D risk at earlier follow-up among those without obesity. T2D prevention and control for Mexican American adults should consider the role of chronic sleep loss.

Crateva unilocularis is naturally distributed in Southern China, which is an elite natural tree with high edible and medicinal value. In this study, whole chloroplast (cp) genome of Crateva unilocularis was assembled and characterized on the basis of Illumina pair-end sequencing data. The complete cp genome was 156,417 bp in length, containing a large single-copy region (LSC) of 85,607 bp and a small single-copy region (SSC) of 18,164 bp, which were separated by a pair of 26,323 bp inverted repeat regions (IRs). The genome contained 128 genes, including 85 protein-coding genes, 35 tRNA genes, and 8 rRNA genes. The overall GC content is 36.32%, while the corresponding values of the LSC, SSC, and IR regions were 33.98, 29.45, and 42.48%, respectively. The maximum-likelihood phylogenetic analysis showed a strong sister relationship with Crateva tapia. These findings provide a foundation for further investigation of cp genome evolution in Crateva unilocularis and other higher plants.

Fraxinus malacophylla is one of the commonly used ecological restoration tree species in rocky desertification areas. It has high medicinal and timber value. And has high marketization prospects. T...

Background: Intracranial Atherosclerotic Stenosis (ICAS) is an important risk factor for cognitive impairment. However, it is unclear whether patients with ICAS are more likely to develop cognitive impairment after an acute, non-disabling ischemic stroke (minor stroke). Objective: We aimed to investigate the association between ICAS and post-stroke cognitive impairment. Methods: In this cross-sectional study, patients with acute, non-disabling ischemic stroke underwent two cognitive tests and imaging evaluation for ICAS, within two weeks after the stroke. To determine the association between ICAS and post-stroke cognitive impairment, we performed a multivariate logistic regression analysis adjusted for several demographic and vascular risk factors. Results: Of the 164 patients with minor stroke in this study, 98 (59.76%) were diagnosed with poststroke cognitive impairment (Montreal Cognitive Assessment score Conclusion: In this cross-sectional study of a population that has experienced a minor stroke, our findings demonstrated a positive association between ICAS and post-stroke cognitive impairment.

Background Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolus (PE) is a serious complication in hospitalized stroke patients. This study is designed to examine the incidence of VTE and the effectiveness of chemo thromboprophylaxis in this population. Methods From January 2015 to April 2018, we calculate the Caprini score for every admitted patient to evaluate VTE risk. For analysis Demographic information, Caprini score, national institutes of health stroke scale (NIHSS) score, prothrombin time (PT), thrombin time (TT), D-Dimer and medical co-morbidity are noted. Results Of 3,824 inpatients during the study period, 21 patients (0.55%) have VTE complications. Among patients (n=148) with a Caprini score between 0 and 2, 1 patient (0.68%) have VTE. VTE (52.38%) most commonly occurred in patients of Caprini score 7-8 group. In patients with VTE (n=21) age, Caprini score, NIHSS score, National Early Warning Score (NEWS) score, PT, TT, D-Dimer are significantly higher than those (n=3,803) without VTE (P Conclusions The Caprini score is highly recommended to assess the risk of venous thrombosis in stroke patients. Early mechanical and chemical prophylaxis are recommended for patients to reduce the incidence of venous thrombosis.

As a putative marker of cerebral small vessel disease, cerebral microbleeds (CMBs) have been associated with vascular cognitive impairment. Both iron accumulation and amyloid protein precursor (APP) dysregulation are recognized as pathological hallmarks underlying the progression of CMBs, but their cross-talk is not yet understood. In this study, we found a profound increase of amyloid formation with increasing FeCl3 treatment, and a distinct change in APP metabolism and expression of iron homeostasis proteins (ferritin, Fpn1, iron regulatory protein) was observed at the 300 uM concentration of FeCl3. Further results revealed that extracellular iron accumulation might potentially induce binding of APP to BACE1 for amyloid formation and decrease the capability of APP/Fpn1 in mediating iron export. Our findings in this study, reflecting a probable relationship between iron dyshomeostasis and amyloid pathology, may help shed light on the underlying pathogenesis of CMBs in vascular cognitive impairment.

Using a longitudinal sample of young Chinese students (fall and spring in grades 1 and 2: times 1–4, respectively) and growth curve analysis, this study examined whether the initial status and growth rates of compounding awareness from time 1 to time 4 uniquely contribute to reading comprehension at time 4 and whether word-reading efficiency at time 4 mediates the association between initial status and growth in compounding awareness and reading comprehension at time 4. The results indicated that initial status and growth rates of compounding awareness made a significant direct contribution to reading comprehension at the end of second grade after controlling for IQ, phonological awareness, and vocabulary knowledge. The relationship between initial status and growth rates of compounding awareness and reading comprehension were fully mediated by word-reading efficiency. The findings underscore the importance of growth in compounding awareness for reading comprehension and add to the literature about the nature of the morphological awareness and reading comprehension relationship in Chinese.

Previous research has shown that the presence of English word spellings facilitates children’s oral vocabulary learning. Whether a similar orthographic facilitation effect may exist in Chinese is interesting but not intuitively obvious due to the character writing system representing morphosyllabic but not phoneme-size information, and the more direct semantic-orthography mapping but less consistent orthography and pronunciation correspondence in Chinese. The current study aims to examine whether semantic and phonological information provided by character radicals affects oral vocabulary learning of Chinese children. Twenty-four second graders studied made-up associations between 12 spoken labels and pictures accompanied either by accurate phonological information characters, misleading phonological information characters, or no orthography. Half of phonologically accurate or misleading characters were semantically accurate or misleading. Pictures prompted recall of spoken labels without orthography present on tests. Results showed that exposure to characters which accurately represent sounds and meanings during learning did not enhance recall of the spoken labels compared to no orthography in early trials. But exposure to characters, which misrepresent sounds and meanings, significantly impeded vocabulary learning compared to no orthography.

Micro-milling is widely used in aerospace and precision optical part manufacturing. Residual stress is an important index of surface integrity, which signally affects the performance of the micro-parts. This paper presents an analytical model to predict micro-milling residual stresses considering tool edge radius, material strengthening effects, and initial stress. A micro-milling cutting force prediction model is proposed, in which tool edge radius and material strengthening effects are taken into account. The imaginary heat source is utilized to estimate the temperature distribution in the workpiece. This model considers the prediction results of cutting force and temperature as thermomechanical loads experienced by the workpiece. Also, the effect of initial stress is taken into account during the estimation of residual stresses. After loading, unloading, and stresses release, the results of residual stresses in micro-milling are finally obtained. Both the micro-milling cutting force and residual stresses prediction results are validated by NAK80 steel on a three-axis ultra-precision machine. The predicted results capture the experiment results well in terms of distribution and value. Finally, the model is analyzed and discussed. The influences of tool edge radius, rake angle, feed per tooth, and spindle speed on residual stresses are preliminarily explored.

Rapid and convenient biosensing platforms could be beneficial to timely diagnosis and treatment of diseases in virtually any care settings. Sandwich immunoassays, the most commonly used methods for protein detection, often rely on expensive tags such as enzyme and tedious wash and incubation procedures operated by skilled labor. In this report, we revolutionized traditional sandwich immunoassays by providing a wash-free homogeneous colorimetric immunoassay method without requirement of any separation steps. The proposed strategy was realized by controlling the growth of gold nanoparticles (AuNPs) to mediate the interparticle spacing in the protein-AuNP oligomers. We have demonstrated the successful in vitro detection of cancer biomarker in serum samples from patients with high clinical sensitivity and specificity.

A thermal model that reveals workpiece temperature variation in bull-nose end milling is presented in this paper. Both machining history and cutting tool are discretized into elements to tackle the problems of interrupted cutting process and complex cutter geometry. In the proposed modeling methodology, shear plane heat source is considered as moving instantaneous rectangular heat source. Image heat source is applied to deal with boundary issues of heat conduction in workpiece. The proposed model is validated by machining 300 M steel under dry cutting state. Good agreement between the estimated and measured workpiece temperatures indicates that the analytical model can provide accurate predicted results. The effects of spindle speed and feed rate on workpiece temperature are theoretically and experimentally investigated. Some conclusions of this study are summarized as follows: (1) In the studied range of processing parameters, workpiece temperature increases with increasing spindle speed and decreases with increasing feed rate. (2) Temperature in workpiece under stable milling state decreases exponentially with increasing horizontal distance between inner point and machined surface.