Divergent Geminal Alkynylation-Allylation and Acylation-Allylation of Carbenes: Evolution and Roles of Two Transition-Metal Catalysts.

Cooperative bimetallic catalysis to access novel reactivities is a powerful strategy for reaction development in transition-metal-catalyzed chemistry. Particularly, elucidation of the evolution of two transition-metal catalysts and understanding their roles in dual catalysis are among the most fundamental goals for bimetallic catalysis. Herein, a novel three-component reaction of a terminal alkyne, a diazo ester, and an allylic carbonate was successfully developed via cooperative Cu/Rh catalysis with Xantphos as the ligand, providing a highly efficient strategy to access 1,5-enynes with an all-carbon quaternary center that can be used as immediate synthetic precursors for complex cyclic molecules. Notably, a Meyer-Schuster rearrangement was involved in the reactions using propargylic alcohols, resulting in an unprecedented acylation-allylation of carbenes. Mechanistic studies suggested that in the course of the reaction Cu(I) species might aggregate to some types of Cu clusters and nanoparticles (NPs), while the Rh(II)2 precursor can dissociate to mono-Rh species, wherein Cu NPs are proposed to be responsible for the alkynylation of carbenes and work in cooperation with Xantphos-coordinated dirhodium(II) or Rh(I)-catalyzed allylic alkylation.

Adherence to a Mediterranean diet is associated with a lower risk of diabetic kidney disease among individuals with hyperglycemia: a prospective cohort study.

BACKGROUND: Type 2 diabetes is associated with a variety of complications, including micro- and macrovascular complications, neurological manifestations and poor wound healing. Adhering to a Mediterranean Diet (MED) is generally considered an effective intervention in individuals at risk for type 2 diabetes mellitus (T2DM). However, little is known about its effect with respect to the different specific manifestations of T2DM. This prompted us to explore the effect of MED on the three most significant microvascular complications of T2DM: diabetic retinopathy (DR), diabetic kidney disease (DKD), and vascular diabetic neuropathies (DN). METHODS: We examined the association between the MED and the incidence of these microvascular complications in a prospective cohort of 33,441 participants with hyperglycemia free of microvascular complications at baseline, identified in the UK Biobank. For each individual, we calculated the Alternate Mediterranean Diet (AMED) score, which yields a semi-continuous measure of the extent to which an individual's diet can be considered as MED. We used Cox proportional hazard models to analyze hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for demographics, lifestyle factors, medical histories and cardiovascular risk factors. RESULTS: Over a median of 12.3 years of follow-up, 3,392 cases of microvascular complications occurred, including 1,084 cases of diabetic retinopathy (DR), 2,184 cases of diabetic kidney disease (DKD), and 632 cases of diabetic neuropathies (DN), with some patients having 2 or 3 microvascular complications simultaneously. After adjusting for confounders, we observed that higher AMED scores offer protection against DKD among participants with hyperglycemia (comparing the highest AMED scores to the lowest yielded an HR of 0.79 [95% CIs: 0.67, 0.94]). Additionally, the protective effect of AMED against DKD was more evident in the hyperglycemic participants with T2DM (HR, 0.64; 95% CI: 0.50, 0.83). No such effect, however, was seen for DR or DN. CONCLUSIONS: In this prospective cohort study, we have demonstrated that higher adherence to a MED is associated with a reduced risk of DKD among individuals with hyperglycemia. Our study emphasizes the necessity for continued research focusing on the benefits of the MED. Such efforts including the ongoing clinical trial will offer further insights into the role of MED in the clinical management of DKD.

A Self-Rectifying Synaptic Memristor Array with Ultrahigh Weight Potentiation Linearity for a Self-Organizing-Map Neural Network.

Two-terminal self-rectifying (SR)-synaptic memristors are preeminent candidates for high-density and efficient neuromorphic computing, especially for future three-dimensional integrated systems, which can self-suppress the sneak path current in crossbar arrays. However, SR-synaptic memristors face the critical challenges of nonlinear weight potentiation and steep depression, hindering their application in conventional artificial neural networks (ANNs). Here, a SR-synaptic memristor (Pt/NiOx/WO3-x:Ti/W) and cross-point array with sneak path current suppression features and ultrahigh-weight potentiation linearity up to 0.9997 are introduced. The image contrast enhancement and background filtering are demonstrated on the basis of the device array. Moreover, an unsupervised self-organizing map (SOM) neural network is first developed for orientation recognition with high recognition accuracy (0.98) and training efficiency and high resilience toward both noises and steep synaptic depression. These results solve the challenges of SR memristors in the conventional ANN, extending the possibilities of large-scale oxide SR-synaptic arrays for high-density, efficient, and accurate neuromorphic computing.

[Genetic analysis of a fetus with cryptophthalmos due to variants of FREM2 gene].

OBJECTIVE: To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography. METHODS: A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy. RESULTS: The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c.4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+PM2_Supporting+PM5+PP3+PP4; PM2_Supporting+PM3+PP3+PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. CONCLUSION: The FREM2: c.4537G>A and c.7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Comparison of Colonoscopy, Fecal Immunochemical Test, and Risk-Adapted Approach in a Colorectal Cancer Screening Trial (TARGET-C).

BACKGROUND & AIMS: The screening yield and related cost of a risk-adapted screening approach compared with established screening strategies in population-based colorectal cancer (CRC) screening are not clear. METHODS: We randomly allocated 19,373 participants into 1 of the 3 screening arms in a 1:2:2 ratio: (1) one-time colonoscopy (n = 3883); (2) annual fecal immunochemical test (FIT) (n = 7793); (3) annual risk-adapted screening (n = 7697), in which, based on the risk-stratification score, high-risk participants were referred for colonoscopy and low-risk ones were referred for FIT. Three consecutive screening rounds were conducted for both the FIT and the risk-adapted screening arms. Follow-up to trace the health outcome for all the participants was conducted over the 3-year study period. The detection rate of advanced colorectal neoplasia (CRC and advanced precancerous lesions) was the main outcome. The trial was registered in the Chinese Clinical Trial Registry (number: ChiCTR1800015506). RESULTS: In the colonoscopy, FIT, and risk-adapted screening arms over 3 screening rounds, the participation rates were 42.4%, 99.3%, and 89.2%, respectively; the detection rates for advanced neoplasm (intention-to-treat analysis) were 2.76%, 2.17%, and 2.35%, respectively, with an odds ratio (OR)colonoscopy vs FIT of 1.27 (95% confidence interval [CI]: 0.99-1.63; P = .056), an ORcolonoscopy vsrisk-adapted screening of 1.17 (95% CI, 0.91-1.49; P = .218), and an ORrisk-adapted screeningvs FIT of 1.09 (95% CI, 0.88-1.35; P = .438); the numbers of colonoscopies needed to detect 1 advanced neoplasm were 15.4, 7.8, and 10.2, respectively; the costs for detecting 1 advanced neoplasm from a government perspective using package payment format were 6928 Chinese Yuan (CNY) ($1004), 5821 CNY ($844), and 6694 CNY ($970), respectively. CONCLUSIONS: The risk-adapted approach is a feasible and cost-favorable strategy for population-based CRC screening and therefore could complement the well-established one-time colonoscopy and annual repeated FIT screening strategies. (Chinese Clinical Trial Registry; ChiCTR1800015506).

Sensitivity-enhanced nanoplasmonic biosensor using direct immobilization of two engineered nanobodies for SARS-CoV-2 spike receptor-binding domain detection.

Sensitive, rapid, and easy-to-implement biosensors are critical in responding to highly contagious and fast-spreading severe acute respiratory syndrome coronavirus (SARS-CoV-2) mutations, enabling early infection screening for appropriate isolation and treatment measures to prevent the spread of the virus. Based on the sensing principle of localized surface plasmon resonance (LSPR) and nanobody immunological techniques, an enhanced sensitivity nanoplasmonic biosensor was developed to quantify the SARS-CoV-2 spike receptor-binding domain (RBD) in serum within 30 min. The lowest concentration in the linear range can be detected down to 0.01 ng/mL by direct immobilization of two engineered nanobodies. Both the sensor fabrication process and immune strategy are facile and inexpensive, with the potential for large-scale application. The designed nanoplasmonic biosensor achieved excellent specificity and sensitivity for SARS-CoV-2 spike RBD, providing a potential option for accurate early screening of the novel coronavirus disease 2019 (COVID-19).

An Improved YOLOv5-Based Underwater Object-Detection Framework.

To date, general-purpose object-detection methods have achieved a great deal. However, challenges such as degraded image quality, complex backgrounds, and the detection of marine organisms at different scales arise when identifying underwater organisms. To solve such problems and further improve the accuracy of relevant models, this study proposes a marine biological object-detection architecture based on an improved YOLOv5 framework. First, the backbone framework of Real-Time Models for object Detection (RTMDet) is introduced. The core module, Cross-Stage Partial Layer (CSPLayer), includes a large convolution kernel, which allows the detection network to precisely capture contextual information more comprehensively. Furthermore, a common convolution layer is added to the stem layer, to extract more valuable information from the images efficiently. Then, the BoT3 module with the multi-head self-attention (MHSA) mechanism is added into the neck module of YOLOv5, such that the detection network has a better effect in scenes with dense targets and the detection accuracy is further improved. The introduction of the BoT3 module represents a key innovation of this paper. Finally, union dataset augmentation (UDA) is performed on the training set using the Minimal Color Loss and Locally Adaptive Contrast Enhancement (MLLE) image augmentation method, and the result is used as the input to the improved YOLOv5 framework. Experiments on the underwater datasets URPC2019 and URPC2020 show that the proposed framework not only alleviates the interference of underwater image degradation, but also makes the mAP@0.5 reach 79.8% and 79.4% and improves the mAP@0.5 by 3.8% and 1.1%, respectively, when compared with the original YOLOv8 on URPC2019 and URPC2020, demonstrating that the proposed framework presents superior performance for the high-precision detection of marine organisms.

Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma.

Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.

In Situ Regeneration of Silicon Microring Biosensors Coated with Parylene C.

Optical biosensors support disease diagnostic applications, offering high accuracy and sensitivity due to label-free detection and their optical resonance enhancement. However, optical biosensors based on noble metal nanoparticles and precise micro-electromechanical system technology are costly, which is an obstacle for their applications. Here, we proposed a biosensor reuse method with nanoscale parylene C film, taking the silicon-on-insulator microring resonator biosensor as an example. Parylene C can efficiently adsorb antibody by one-step modification without any surface treatment, which simplifies the antibody modification process of sensors. Parylene C (20 nm thick) was successfully coated on the surface of the microring to modify anti-carcinoembryonic antigen (anti-CEA) and specifically detect CEA. After sensing, parylene C was successfully removed without damaging the sensing surface for the sensor reusing. The experimental results demonstrate that the sensing response did not change significantly after the sensor was reused more than five times, which verifies the repeatability and reliability of the reusable method by using parylene C. This framework can potentially reduce the cost of biosensors and promote their further applications.

A ratiometric fluorescent probe based on peptide modified MnFe2O4 nanoparticles for matrix metalloproteinase-7 activity detection in vitro and in vivo.

Abnormal expression of matrix metalloproteinases plays an important role in tumor invasion and metastasis. In this report, a peptide modified MnFe2O4 ratiometric fluorescent nanoprobe is developed for noninvasively visualizing the distribution of matrix metalloproteinase-7 (MMP-7) in vitro and in vivo. A fluorescein isothiocyanate (FITC) modified peptide containing the specific motif VPLSLTMG for MMP-7 cleavage was conjugated with MnFe2O4 nanoparticles (NPs) to establish a Förster resonance energy transfer (FRET) system for sensing the protease. The rhodamine B (RhB) modified targeting peptide immobilized on the nanoparticle surface was not only used as an internal reference for forming a ratiometric fluorescence system together with the FITC dye, but also used for enhancing the tumor targeting ability. The tumor accumulation amount of the as-developed ratiometric fluorescent probe (termed MnFe2O4-pep-dyes) can be measured by T2-weighted magnetic resonance (T2-weighted MR) imaging because MnFe2O4 NPs display an excellent T2-weighted MR contrast ability. In the presence of MMP-7, FITC detached from the MnFe2O4 surface resulting in the recovery of FITC fluorescence, while no obvious change of the RhB fluorescence was observed. The recovery ratio of FITC to RhB fluorescence intensity is linearly dependent on the MMP-7 concentration within the range of 0.1 to 15 nM in buffer and 5 × 102 to 1 × 104 cells in cell lysates with a limit of detection of 0.1 nM and 436 cells, respectively. MnFe2O4-pep-dyes was further applied to spatially observe MMP-7 expression in a tumor-bearing mouse by in vivo fluorescence imaging with external magnetic field assistance for demonstrating its practicability.

Head-to-head comparison of a risk-adapted screening strategy using various risk prediction models in detecting colorectal neoplasm.

BACKGROUND AND AIM: The risk-adapted screening strategy showed satisfying colorectal cancer (CRC) screening yield and efficiency. We therefore further explored the diagnostic performance variation of this strategy using different risk prediction models. METHODS: A literature search was conducted to identify studies evaluating risk models for advanced colorectal neoplasm (ACN). The included models were retrospectively validated in a subset sample (N = 3219) from a population-based CRC screening trial in China. Diagnosis-related indictors were compared between the risk-adapted screening strategy using different models and the fecal immunochemical test (FIT)-only strategy. For simulated populations with ACN prevalence of 3% to 12%, the trade-off of additional false positives for each additional true positive were calculated. RESULTS: We included 14 eligible risk models with the area under the curves ranging 0.570 to 0.652 in the validation set. The overall sensitivities of the risk-adapted screening strategy using different risk models for ACN varied from 46.0% to 69.8%, higher than FIT (21.9%), but at the expense of specificities (51.6% to 78.3% vs 97.1%). For population having ACN prevalence of 3%, risk-adapted screening strategies needed 20.5 to 31.1 additional false positives for each additional true positive compared with FIT, and respective number would substantially reduce (4.7 to 7.1) as the ACN prevalence increased to 12%. CONCLUSIONS: Risk-adapted screening strategy using the current risk models showed improved sensitivity for ACN compared with FIT, at the cost of increased colonoscopy workload. The optimal strategy for screening practice should be tailored considering the disease burden and availability of healthcare resources.

Controllable bisubstrate multi-colorimetric assay based on peroxidase-like nanozyme and complementary colorharmonic principle for semi-quantitative detection of H2O2 with the naked eye.

Naked-eye semi-quantitative (NEQ) assays should exhibit vivid color variations and one-to-one correspondence between the analyte concentrations and the color display. Herein, we report a bisubstrate multi-colorimetric system, constituted by 3,3',5,5'-tetramethylbenzidine (TMB) and dopamine (DA), which carries out a controllable NEQ assay based on the complementary colorharmonic principle. This bisubstrate system is a universal threshold NEQ assay with tunable sensitivity and detection window depending on the H2O2 concentration. The peroxidase-like activity of PEG@Fe3O4 NPs was used to catalyze the oxidations of TMB and DA by H2O2 to the colored products. On the basis of UV-vis spectra data, it was speculated that the oxidation product of TMB (TMB·+) could oxidize DA in this system. The concentration of DA controls the consumption of oxidant (H2O2) and the oxidation of TMB. By controlling the molar ratio of TMB to DA, the bisubstrate system precisely showed multicolor displays (e.g., three-color display: orange, gray, and blue) at submillimolar and millimolar concentrations of H2O2. The detection limit and sensitivity for H2O2 were 0.4 mM and 0.1 mM, respectively. Next, the system was applied to the threshold detection of hypoglycemia (orange), normal (gray), and hyperglycemia (blue) in spiked samples on both gel- and paper-based test strips. Digitalized colorimetric results using the red-green-blue (RGB) analysis with smartphone application were achieved. This work provides a new strategy of multi-colorimetric assay that takes advantages of controllability, threshold detection, vivid color variations, and reproducibility (CVs were 1.1-2.1%), which could be potentially useful for in-field and point-of-care applications.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Dynamic phase manipulation of vertical-cavity surface-emitting lasers via on-chip integration of microfluidic channels.

Vertical-cavity surface-emitting lasers (VCSELs) play a key role in the development of the next generation of optoelectronic technologies, thanks to their unique characteristics, such as low-power consumption, circular beam profile, high modulation speed, and large-scale two-dimensional array. Dynamic phase manipulation of VCSELs within a compact system is highly desired for a large variety of applications. In this work, we incorporate the emerging microfluidic technologies into the conventional VCSELs through a monolithic integration approach, enabling dynamic phase control of lasing emissions with low power consumption and low thermal generation. As a proof of concept, a beam steering device is experimentally demonstrated by integrating microfluidic channel on a coherently coupled VCSELs array. Experimental results show that the deflection angles of the laser beam from the chip can be tuned from 0° to 2.41° under the injection of liquids with different refractive index into the microchannel. This work opens an entirely new solution to implement a compact laser system with real-time wavefront controllability. It holds great potentials in various applications, including optical fiber communications, laser printing, optical sensing, directional displays, ultra-compact light detection and ranging (LiDAR).

Prodrug polymeric micelles integrating cancer-associated fibroblasts deactivation and synergistic chemotherapy for gastric cancer.

BACKGROUND: The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. METHODS: Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. RESULTS: Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. CONCLUSION: TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC.

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening: A cross-sectional population-based analysis.

OBJECTIVE: Integration of risk stratification into fecal immunochemical test (FIT) might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer (CRC) screening. A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment (QRA) and FIT, FIT-only and QRA-only strategies in a CRC screening program in China. METHODS: The study included 29,626 individuals aged 40-74 years and invited to participate in a CRC screening program in China. Participants were first invited to undertake QRA and one-time FIT (OC-sensor). Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy. Participation, detection rate, and resource demand for colonoscopy were calculated and compared. RESULTS: Of the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 completed the FIT-only strategy. For the parallel combination, FIT-only, and QRA-only strategies, the overall positivity rates were 10.2% (2,928/28,806), 5.4% (1,096/20,214), and 6.8% (1,944/28,795), respectively; the yield of advanced neoplasm per 10,000 invitees were 46.9 [95% confidence interval (95% CI): 39.8-55.4], 36.8 (95% CI: 30.5-44.4), and 12.2 (95% CI: 8.8-16.8), respectively; the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7% (95% CI: 4.0%-5.6%), 9.9% (95% CI: 8.3%-11.9%), and 1.9% (95% CI: 1.3%-2.6%), respectively; the number of colonoscopies required to detect one advanced neoplasm was 11.4 (95% CI: 9.8-13.4), 5.7 (95% CI: 4.8-6.7), and 28.4 (95% CI: 20.7-39.2), respectively. CONCLUSIONS: The parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.

The association between fasting blood glucose trajectory and cancer risk in Chinese population without diabetes.

To examine the associations between fasting blood glucose (FBG) trajectories, the changes in FBG over time and the risk of cancer, particularly for gastrointestinal cancer, we enrolled 69,742 participants without diabetes from the Kailuan cohort. FBG trajectories (2006-2010) were modeled by group-based trajectory modeling, and five trajectories were identified: low-increasing (n = 6,275), moderate-stable (n = 44,120), moderate-increasing (n = 10,149), elevated-decreasing (n = 5,244) and elevated-stable (n = 3,954). A total of 1,364 cancer cases were accumulated between 2010 and 2015, including 472 gastrointestinal cancer cases. We used Cox proportional hazards regression models to evaluate the associations between FBG trajectory patterns and the risk of cancer. We further assessed the associations while carefully controlling for initial body mass index (BMI) in 2006 and for changes in BMI during 2006-2010. Relative to the moderate-stable group, we found a higher hazard ratio (HR) for overall cancer in the low-increasing group (HR = 1.26, 95% confidence interval (CI) 1.06-1.50); and for gastrointestinal cancer in the elevated-stable group (HR = 1.66, 95% CI 1.22-2.26). Moreover, among participants with an initial BMI ≥25 kg/m2 , a positive association with the low-increasing group was observed for both overall cancer and gastrointestinal cancer (HR = 1.54, 95% CI 1.17-2.04; HR = 1.65, 95% CI 1.02-2.66; respectively); among participants with a stable BMI (4.40% loss-5.15% gain), a positive association with the elevated-stable group was observed both for overall cancer and gastrointestinal cancer (HR = 1.43, 95% CI 1.10-1.87; HR = 1.95, 95% CI 1.33-2.86; respectively). Our study observed that FBG trajectories were associated with cancer risk among participants without diabetes, and BMI may modify the associations.

Comparative Evaluation of Participation and Diagnostic Yield of Colonoscopy vs Fecal Immunochemical Test vs Risk-Adapted Screening in Colorectal Cancer Screening: Interim Analysis of a Multicenter Randomized Controlled Trial (TARGET-C).

INTRODUCTION: In colorectal cancer screening, implementing risk-adapted screening might be more effective than traditional screening strategies. We aimed to compare the effectiveness of a risk-adapted screening strategy with colonoscopy and fecal immunochemical test (FIT) in colorectal cancer screening. METHODS: A randomized controlled trial was conducted in 6 centers in China since May 2018. Nineteen thousand five hundred forty-six eligible participants aged 50-74 years were recruited and randomly allocated into 1 of the 3 screening groups in a 1:2:2 ratio: (i) one-time colonoscopy (n = 3,916), (ii) annual FIT (n = 7,854), and (iii) annual risk-adapted screening (n = 7,776). Based on the risk-stratification score, high-risk subjects were referred for colonoscopy and low-risk ones were referred for FIT. All subjects with positive FIT were referred for diagnostic colonoscopy. The detection rate of advanced neoplasm was the primary outcome. The study is registered with the China Clinical Trial Registry (www.chictr.org.cn Identifier: ChiCTR1800015506). RESULTS: For baseline screening, the participation rates of the colonoscopy, FIT, and risk-adapted screening groups were 42.5% (1,665/3,916), 94.0% (7,386/7,854), and 85.2% (6,628/7,776), respectively. For the intention-to-screen analysis, the detection rates of advanced neoplasm were 2.40% (94/3,916), 1.13% (89/7,854), and 1.66% (129/7,776), with odds ratios (95% confidence intervals) of 2.16 (1.61-2.90; P < 0.001) for colonoscopy vs FIT, 1.45 (1.10-1.90; P < 0.001) for colonoscopy vs risk-adapted screening, and 1.49 (1.13-1.97; P < 0.001) for risk-adapted screening vs FIT, respectively. The numbers of subjects who required a colonoscopic examination to detect 1 advanced neoplasm were 18 in the colonoscopy group, 10 in the FIT group, and 11 in the risk-adapted screening group. DISCUSSION: For baseline screening, the risk-adapted screening approach showed a high participation rate, and its diagnostic yield was superior to that of FIT at a similarly low load of colonoscopy.

High-performance plasmonic refractive index sensors via synergy between annealed nanoparticles and thin films.

Plasmonic nanostructure-based refractive index (RI) sensors are the core component of biosensor systems and play an increasingly important role in the diagnosis of human disease. However, the costs of traditional plasmonic RI sensors are not acceptable to everyone due to their expensive fabrication process. Here, a novel low-cost and high-performance visible-light RI sensor with a particle-on-film configuration was experimentally demonstrated. The sensor was fabricated by transferring annealed Au nanoparticles (NPs) onto a thin gold film with polymethyl methacrylate (PMMA) as a support. RI sensitivities of approximately 209 nm/RIU and 369 nm/RIU were achieved by reflection and transmission spectrum measurements, respectively. The high sensitivity is due to the strong plasmon-mediated energy confinement within the interface between the particles and the film. The possibility of wafer-scale production and high working stability achieved by the transfer process, together with the high sensitivity to the environmental RI, provides an extensive impact on the realization of universal biosensors for biological applications.

Smart design of exquisite multidimensional multilayered sand-clock-like upconversion nanostructures with ultrabright luminescence as efficient luminescence probes for bioimaging application.

A facile scalable approach is presented for the rational design of multidimensional, multilayered sand-clock-like UCNPs (denoted as UCCKs) bounded with high index facets, with a tunable Nd3+ content, and without a template or multiple complicated reaction steps. This was achieved using the seed-mediated growth and subsequent longitudinal direction epitaxial growth with the assistance of oleic acid and NH4F. The as-formed UCCKs composed of an inner layer (NaYF4:Yb,Er,Ca), an intermediate layer (NaYF4:Yb,Ca), and an outer layer (NaNdF4:Yb,Ca). The outer shell, enriched with Nd3+ sensitizer, augmented the near-infrared (NIR) photon absorption, whereas the intermediate shell, enriched with Yb3+, acted as a bridge for energy transfer from Nd3+ to Er3+ emitter in the inner core alongside with precluding any deleterious energy back-transfer from Er3+ or quenching effect from Nd3+. These unique structural and compositional properties of UCCKs endowed the UCL intensity of UCCKs by 22 and 10 times higher than that of hexagonal UCNP core (NaYF4:Yb,Er,Ca) and hexagonal UCNP core-shell (NaYF4:Yb,Er,Ca@NaYF4:Yb,Ca), respectively. Intriguingly, the UCL intensity increased significantly with increasing the content of Nd3+ in the outer shell. The silica-coated UCCKs were used as excellent long-term luminescence probes for the in vitro bioimaging without any noteworthy cytotoxicity. The presented approach may pave the road for controlling the synthesis of multidimensional UCCKs for various applications. Graphical abstract We developed novel multidimensional multilayered sand-clock-like upconversion nanostructures composed of a spherical inner core (NaYF4:Yb,Er,Ca), hexagonal intermediate shell (NaYF4:Yb,Ca) and two up-down outer shell (NaNdF4:Yb,Ca) with controllable Nd3+ as an efficient and safe probe for bioimaging applications without any quenching effect.