Association between healthy lifestyle and frailty in adults and mediating role of weight-adjusted waist index: results from NHANES.

BACKGROUND: The relationship between healthy lifestyle and frailty remains unclear. Healthy weight is crucial for overall well-being, but using body mass index (BMI) to evaluate weight management is inefficient. This study clarifies the association between healthy lifestyle or its factors (non-smoking, moderate drinking, healthy weight, healthy diet, sufficeint physical activity, and non-sedentary) and frailty, and the feasibility of using the weight-adjusted waist index (WWI) reflecting central obesity as an intermediate indicator. METHODS: This study included 4,473 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). Healthy lifestyle quality was assessed by summing the scores of each healthy lifestyle factor. Frailty was assessed using a 49-item frailty index (FI), categorizing participants into robust, pre-frail, and frail. Logistic regression to investigate the association between healthy lifestyle or its factors, WWI, and frailty. Smooth curve fitting and threshold effect analyses were used to elucidate the nonlinear association. Subgroup and two other sensitivity analyses were conducted to confirm the stability of the results. A causal mediation model examined the proportion of frailty mediated by WWI. RESULTS: The study identified 13.98% of the participants as frail. Optimal healthy lifestyle and frailty were negatively associated (OR: 0.39, 95%CI: 0.27-0.58). Five healthy lifestyle factors (non-smoking, healthy weight, healthy diet, sufficient physical activity, and non-sedentary) were associated with a lower prevalence of frailty, with odds ratios (OR) ranging from 0.48 to 0.61. We also analyzed the association between a healthy lifestyle and WWI (OR: 0.32, 95%CI: 0.27-0.37), WWI and frailty (OR: 1.85, 95%CI: 1.59-2.16). A positive association between WWI and FI was observed beyond the inflection point (9.99) (OR: 0.03, 95%CI: 0.02-0.03). Subgroup and sensitivity analyses confirmed stable associations between healthy lifestyle, WWI, and frailty. WWI partially mediated the association between a healthy lifestyle and frailty (mediating ratio = 20.50-20.65%). CONCLUSIONS: An optimal healthy lifestyle and positive healthy lifestyle factors are associated with a lower incidence of frailty. WWI may mediate the relationship between a healthy lifestyle and frailty.

Trends in prevalence of arthritis by race among adults in the United States, 2011-2018.

BACKGROUND: There is currently a lack of comprehensive prevalence information on arthritis and its various classifications among adults in the U.S., particularly given the notable absence of detailed data regarding the Asian population. We examined the trends in the prevalence of arthritis, including osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and other types of arthritis, among U.S. adults by race between 2011 and 2018. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES), spanning from 2011 to 2018. Our study focused on a nationally representative sample of U.S. adults aged 20 and older. Participants who answered "y es" to the research question "Doctors ever said you had arthritis?" were classified as having arthritis. Further classification into specific diseases was based on responses to the question "Which type of arthritis was it?" with options including "OA or degenerative arthritis, " "RA, " "PsA, " or "Other. " RESULTS: We analyzed 22,566 participants from NHANES (2011-2018), averaging 44.8 years, including 10,927 males. The overall arthritis prevalence rose significantly from 22.98% (95% CI: 21.47-24.55%) in 2011-12 to 27.95% (95% CI: 26.20-29.76%) in 2017-18 (P for trend < 0.001). OA increased from 12.02% (95% CI: 10.82-13.35%) in 2011 to 14.93% (95% CI: 13.47-16.51%) in 2018 (P for trend < 0.001). RA and PsA remained stable (P for trend = 0.220 and 0.849, respectively), while other arthritis rose from 2.03% (95% CI: 1.54-2.67%) in 2011-12 to 3.14% (95% CI: 2.56-3.86%) in 2017-18 (P for trend = 0.001). In Whites, Asians, and other races , arthritis and RA prevalence increased significantly (P for trend < 0.05). OA and other arthritis rose in Whites and other races (P for trend < 0.05), but no significant change occurred in the black population. The prevalence of PsA remained stable across all racial groups, with no statistically significant changes. CONCLUSIONS: In this nationally representative U.S. adult survey spanning 2011 to 2018, we identified a rising prevalence trend in arthritis, OA, and other arthritis, with notable variations among different racial groups.

Exogenous and Endogenous Dual-Activated Nanoladder for Precise Imaging of Mitochondrial Ferroptosis-Related Inhibition miRNA with Tumor Cell Specificity.

Developing precise tumor cell-specific mitochondrial ferroptosis-related inhibition miRNA imaging methods holds enormous potential for anticancer drug screening and cancer treatment. Nevertheless, traditional amplification methods still tolerated the limited tumor specificity because of the "off-tumor" signal leakage resulting from their "always-active" sensing mode. To overcome this limitation, we herein developed a dual (exogenous 808 nm NIR light and endogenous APE1) activated nanoladder for precise imaging of mitochondrial ferroptosis-related miRNA with tumor cell specificity and improved imaging resolution. Exogenous NIR light-activation can regulate the ferroptosis-related inhibition miRNA imaging signals within mitochondria, and endogenous enzyme-activation can confine signals to tumor cells. Based on this dual activation design, off-tumor signals were greatly reduced and tumor-to-background contrast was enhanced with an improved tumor/normal discrimination ratio, realizing tumor cell-specific precise imaging of mitochondrial ferroptosis-related inhibition miRNA.

Light and endogenous enzyme triggered plasmonic antennas for accurate subcellular molecular imaging with enhanced spatial resolution.

Developing accurate tumor-specific molecular imaging approaches holds great potential for evaluating cancer progression. However, traditional molecular imaging approaches still suffer from restricted tumor specificity due to the "off-tumor" signal leakage. In this work, we proposed light and endogenous APE1-triggered plasmonic antennas for accurate tumor-specific subcellular molecular imaging with enhanced spatial resolution. Light activation ensures subcellular molecular imaging and endogenous enzyme activation ensures tumor-specific molecular imaging. In addition, combined with the introduction of plasmon enhanced fluorescence (PEF), off-tumor signal leakage at the subcellular level was effectively reduced, resulting in the significantly enhanced discrimination ratio of tumor/normal cells (∼11.57-fold) which is better than in previous reports, demonstrating great prospects of these plasmonic antennas triggered by light and endogenous enzymes for tumor-specific molecular imaging at the subcellular level.

Review of the Pathogenesis, Diagnosis, and Management of Osteoradionecrosis of the Femoral Head.

Osteoradionecrosis (ORN) of the femoral head is an important issue for orthopedists and radiologists in clinical practice. With the rapid development of technological advances in radiation therapy and the improvement in cancer survival rates, the incidence of ORN is rising, and there is an unmet need for basic and clinical research. The pathogenesis of ORN is complex, and includes vascular injury, mesenchymal stem cell injury, bone loss, reactive oxygen species, radiation-induced fibrosis, and cell senescence. The diagnosis of ORN is challenging and requires multiple considerations, including exposure to ionizing radiation, clinical manifestations, and findings on physical examination and imaging. Differential diagnosis is essential, as clinical symptoms of ORN of the femoral head can resemble many other hip conditions. Hyperbaric oxygen therapy, total hip arthroplasty, and Girdlestone resection arthroplasty are effective treatments, each with their own advantages and disadvantages. The literature on ORN of the femoral head is incomplete and there is no criterion standard or clear consensus on management. Clinicians should gain a better and more comprehensive understanding on this disease to facilitate its early and better prevention, diagnosis, and treatment. This article aims to review the pathogenesis, diagnosis, and management of osteoradionecrosis of the femoral head.

Enzymatically Activated Autonomous-Motion DNAzyme Signal Amplification Strategy for Tumor Cell-Specific Molecular Imaging with Improved Spatial Specificity.

Strategies for achieving tumor-specific molecular imaging based on signal amplification hold great potential for evaluating the risk of tumor metastasis and progression. However, traditional amplification strategies are still constrained with limited tumor specificity because of the off-tumor signal leakage. Herein, an endogenous enzyme-activated autonomous-motion DNAzyme signal amplification strategy (E-DNAzyme) was rationally designed for tumor-specific molecular imaging with improved spatial specificity. The sensing function of E-DNAzyme can be specifically activated by the overexpressed apurinic/apyrimidinic endonuclease 1 (APE1) in the cytoplasm of tumor cells instead of normal cells, ensuring the tumor cell-specific molecular imaging with improved spatial specificity. Of note, benefiting from the target analogue-triggered autonomous motion of the DNAzyme signal amplification strategy, the detection limit can be decreased by approx. ∼7.8 times. Moreover, the discrimination ratio of tumor/normal cells of the proposed E-DNAzyme was ∼3.44-fold higher than the traditional amplification strategy, indicating the prospect of this universal design for tumor-specific molecular imaging.

Fluorescence-Enhanced Dual-Driven "OR-AND" DNA Logic Platform for Accurate Cell Subtype Identification.

Developing an endogenous stimuli-responsive and ultrasensitive DNA sensing platform that contains a logic gate biocomputation for precise cell subtype identification holds great potential for disease diagnosis and prognostic estimation. Herein, a fluorescence-enhanced "OR-AND" DNA logic platform dual-driven by intracellular apurinic/apyrimidinic endonuclease 1 (APE 1) or a DNA strand anchored on membrane protein Mucin 1 (MUC 1) for sensitive and accurate cell subtype identification was rationally designed. The recognition toehold of the traditional activated probe (TP) was restrained by introducing a blocking sequence containing an APE 1 cleavable site (AP-site) that can be either cleaved by APE 1 or replaced by Mk-apt, ensuring the "OR-AND" gated molecular imaging for cell subtype identification. It is worth noting that this "OR-AND" gated design can effectively avoid the missing logical computation caused by membrane protein heterogeneous spatial distribution as a single input. In addition, a benefit from the excellent plasmon-enhanced fluorescence (PEF) ability of Au NSTs is that the detection limit can be decreased by nearly 165 times. Based on this, not only different kinds of MCF-7, HepG2, and L02 cells, but also different breast cancer cell subtypes, including malignant MCF-7, metastatic MDA-MB-231, and nontumorigenic MCF-10A cells, can be accurately identified by the proposed "OR-AND" gated DNA logic platform, indicating the prospect of this simple and universal design in accurate cancer screening.

Optimal Timing of Anterior Cruciate Ligament Reconstruction in Patients With Anterior Cruciate Ligament Tear: A Systematic Review and Meta-analysis.

Importance: The timing of surgery has been regarded as a key factor in anterior cruciate ligament reconstruction (ACLR), and early vs delayed ACLR remains a controversial topic. Objective: To synthesize up-to-date published data from randomized clinical trials (RCTs) comparing early vs elective delayed ACLR for patients with ACL deficiency, in terms of clinical outcomes and complications. Data Sources: The PubMed, Cochrane Library, and Web of Science databases were systematically searched until September 9, 2022. Study Selection: All published RCTs comparing clinical and functional outcomes and complications associated with early ACLR vs elective delayed ACLR. Data Extraction and Synthesis: Two reviewers independently extracted relevant data and assessed the methodological quality following the PRISMA guidelines. Main Outcomes and Measures: Due to the clinical heterogeneity, the random-effects model was preferred. The primary outcomes were functional outcomes and complications. The Mantel-Haenszel test was used to evaluate dichotomous variables and the inverse variance method was used to assess continuous variables. Results: This meta-analysis included 972 participants in 11 RCTs stratified by follow-up duration. The following factors did not differ between early and delayed ACLR: operative time (mean difference, 4.97; 95% CI, -0.68 to 10.61; P = .08), retear (OR, 1.52; 95% CI, 0.52-4.43; P = .44), and infection (OR, 3.80; 95% CI, 0.77-18.79; P = .10). There were also no differences between groups in range of motion, knee laxity, International Knee Documentation Committee (IKDC rating scale), and Tegner score. IKDC score (mean difference, 2.77; 95% CI, 1.89-3.66; P < .001), and Lysholm score at 2-year follow-up (mean difference, 2.61; 95% CI, 0.74-4.48; P = .006) significantly differed between early and delayed ACLR. In addition, the timing of surgery was redefined in the included RCTs and subgroup analyses were performed, which validated the robustness of the principal results. Conclusion and Relevance: This systematic review and meta-analysis found that early ACLR was not superior to delayed ACLR in terms of most factors analyzed, except for IKDC and Lysholm scores. This information should be available to patients with ACL deficiency and clinicians as part of the shared decision-making process of treatment selection.

Spatiotemporally Controlled Ultrasensitive Molecular Imaging Using a DNA Computation-Mediated DNAzyme Platform.

Programming ultrasensitive and stimuli-responsive DNAzyme-based probes that contain logic gate biocomputation hold great potential for precise molecular imaging. In this work, a DNA computation-mediated DNAzyme platform that can be activated by 808 nm NIR light and target c-MYC was designed for spatiotemporally controlled ultrasensitive AND-gated molecular imaging. Particularly, the sensing and recognition function of the traditional DNAzyme platform was inhibited by introducing a blocking sequence containing a photo-cleavable linker (PC-linker) that can be indirectly cleaved by 808 nm NIR light and thus enables the AND-gated molecular imaging. According to the responses toward three designed SDz, nPC-SDz, and m-SDz DNAzyme probes, the fluorescence recovery in diverse cell lines (MCF-7, HeLa, and L02) and inhibitor-treated cells was investigated to confirm the AND-gated sensing mechanism. It is worth noting that thanks to the strand displacement amplification and the ability of gold nanopyramids (Au NBPs) to enhance fluorescence, the fluorescence intensity increased by ∼7.9 times and the detection limit decreased by nearly 40.5 times. Moreover, false positive signals can be also excluded due to such AND-gated design. Furthermore, such a designed "AND-gate" sensing manner can also be applied to spatiotemporally controlled ultrasensitive in vivo molecular imaging, indicating its promising potential in precise biological molecular imaging.

pH Programmed Optical Sensor Arrays for Cancer Plasma Straightforward Discrimination Based on Protein-Responsive Patterns.

Optical cross-reactive sensor arrays inspired by the mammalian olfactory system that can realize straightforward discrimination of plasma from cancer patients hold great potential for point-of-care diseases diagnostics. Herein, a pH programmed fluorescence sensor array based on protein-responsive patterns was designed for straightforward discrimination of different types of cancer plasma. It is worth noting that plasma discrimination can be realized only by programming one nanomaterial using different pH values, which greatly simplifies the programmable design of the sensor array, making it an important highlight of this work. In addition, the mechanism of the pH programmed fluorescence sensor array for protein responsiveness was systematically investigated through molecular docking simulation, fluorescence resonance energy transfer (FRET), and fluorescence lifetime experiments. Most importantly, not only can the differences between plasma from healthy people and and from patients with different cancer species including gastric cancer, liver cancer, breast cancer, and cervical cancer be discriminated by this pH programmed fluorescence sensor array, but also the blind test of unknown plasma samples can be well identified with 100% accuracy, indicating its promising prospect in clinical application.

Osteoradionecrosis of the Hip, a Troublesome Complication of Radiation Therapy: Case Series and Systematic Review.

Background: Osteoradionecrosis of the hip is a serious complication of radiotherapy that is easily overlooked by physicians and patients in the early stages. There are relatively few reports on this subject, so there is no clear scientific consensus for the pathogenesis, early diagnosis, and clinical treatment of hip osteoradionecrosis. In this paper, we report two cases of hip osteoradionecrosis and systematically review the related literature. Case Presentation: We report two cases of hip osteoradionecrosis. One patient successfully underwent total hip arthroplasty in our hospital and recovered well postoperatively. Another patient although we offered a variety of surgical options for this patient, the patient was worried that the bone loss would lead to poor prosthesis fixation, resulting in prosthesis loosening and infection, and therefore ultimately refused surgical treatment. Conclusion: With the development of radiological techniques, the incidence of hip osteoradionecrosis is decreasing year by year, but early diagnosis and rational treatment remain challenging. The effects of non-surgical treatment are limited. Early prevention, early detection, and early intervention are crucial to delay or prevent the emergence of more serious complications.

Slipped capital femoral epiphysis with hypopituitarism in adults: A case report and literature review.

RATIONALE: Slipped capital femoral epiphysis (SCFE) is a common disease in pediatric orthopedics. Most research on SCFE has focused on high-risk groups or the whole population, and studies focusing on adult SCFE patients are rare. In the present study, we report the case of an adult patient with SCFE. PATIENT CONCERN: A 37-year-old man presented to our clinic with persistent pain that was poorly localized to both hips, groin regions, and thighs for more than 1 year. DIAGNOSES: A bilateral hip X-ray examination was performed, and the femoral epiphyses were found to be unfused on both sides. Low levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone, and high levels of thyroid-stimulating hormone, prolactin, and cortisol. INTERVENTIONS: Hormone-substitution therapies (levothyroxine sodium to treat hypothyroidism and testosterone enanthate to treat hypogonadism) were prescribed. Total hip arthroplasty was performed to treat femoral epiphysis slippage. OUTCOMES: After 6 months of postoperative follow-up, the patient's gait improved significantly, and bilateral hip pain was relieved. LESSONS: When treating adults with SCFE, clinicians must be alert to endocrine disorders. Comprehensive imaging evaluation is crucial for the accurate diagnosis and selection of an appropriate treatment.

Primary nonkeratinizing squamous cell carcinoma of the scapular bone: A case report.

BACKGROUND: Squamous cell carcinoma (SCC) of bone is usually caused by metastasis from the lungs, bladder, or other sites. Primary SCC of bone most frequently involves the skull bones, and primary involvement of other sites in the skeletal system is extremely rare. To date, only three such cases have been reported, which makes the diagnosis, treatment, and prognosis of this disease a challenge. CASE SUMMARY: A 76-year-old Chinese man presented to our hospital with nonspecific pain and limited mobility in the right shoulder for 4 mo. He underwent three-dimensional computed tomography reconstruction and magnetic resonance imaging of the right shoulder, which revealed an osteolytic destructive lesion in the right scapula with invasion into the surrounding muscles and soft tissues. Ultrasound-guided core needle biopsy detected a malignant tumor, and immunohistochemical analysis revealed a poorly differentiated SCC. Wide excision of the right scapular bone was performed, and pathological examination of the surgical specimen confirmed the diagnosis. At the last follow-up examination within 2 years, the patient was doing well with the pain significantly relieved in the right shoulder. CONCLUSION: Primary SCC of bone is extremely rare at sites other than the skull. Clinicians must exhaust all available means for the diagnosis of primary SCC of the bone, so greater attention can be paid to its timely and effective management. Regular and adequate follow-up is essential to help rule out metastasis and judge the prognosis.

More Symmetrical "Hot Spots" Ensure Stronger Plasmon-Enhanced Fluorescence: From Au Nanorods to Nanostars.

Plasmon-enhanced fluorescence (PEF) is considered to be a powerful signal amplification technology to overcome intrinsic shortcomings of photobleaching and brightness of the traditional fluorescent dyes. Nevertheless, exploitation of PEF-based probes for bioimaging application is still at a very early stage. In this work, a simple but powerful gold nanostar (Au NST)@SiO2-based PEF probe with 20 symmetric "hot spots" was developed for highly sensitive "lighting up" in situ imaging of intracellular microRNAs (miRNAs). By regulating the thickness of the silica shell, the distance between Au NSTs and fluorescent dyes was controlled, and the optimum fluorescence enhancement (21-fold) was obtained with the silica shell thickness of approximately 22 nm. Thanks to the 20 more powerful "hot spots" that can produce stronger localized electric fields, the Au NST-based PEF probe exhibits stronger PEF effects than the traditional plasmonic nanostructures such as gold nanorods (Au NRs), gold nanobipyramids (Au NBPs), and triangular gold nanoprisms (Au NPRs), resulting in high sensitivity and improved detection limit (LOD) of 0.21 pM for miRNA-21 analysis. Moreover, not only cancer cells (MCF-7 and Hela) and normal cells (L02) with distinct miRNA-21 expression levels can be discriminated but also tumor cells in co-cultured mixtures can be recognized, indicating its promising potential in clinical diagnosis.

Core-Shell Multifunctional Nanomaterial-Based All-in-One Nanoplatform for Simultaneous Multilayer Imaging of Dual Types of Tumor Biomarkers and Photothermal Therapy.

Versatile all-in-one nanoplatforms that inherently possess both diagnostic imaging and therapeutic capabilities are highly desirable for efficient tumor diagnosis and treatment. Herein, we have developed a novel core-shell multifunctional nanomaterial-based all-in-one nanoplatform composed of gold nanobipyramids@polydopamine (Au NBPs@PDA) and gold nanoclusters (Au NCs) for simultaneous in situ multilayer imaging of dual types of tumor biomarkers (using a single-wavelength excitation) with different intracellular spatial distributions and fluorescence-guided photothermal therapy. The competitive combination between target transmembrane glycoprotein mucin1 (MUC1) and its aptamer caused Au NCs (620 nm) labeled with MUC1 aptamer to detach from the surface of Au NBPs@PDA, turning on the red fluorescence. Meanwhile, the hybridization between microRNA-21 (miRNA-21) and its complementary single-stranded DNA triggered the green fluorescence of Au NCs (515 nm). Based on this, simultaneous in situ multilayer imaging of dual types of tumor biomarkers with different intracellular spatial distributions was achieved. In addition, the potential of Au NBPs@PDA/Au NCs was also confirmed by simultaneous multilayer in situ imaging within not only three cell lines (MCF-7, HepG2, and L02 cells) with different expression levels of MUC1 and miRNA-21 but also cancer cells treated with different inhibitors. Moreover, the remarkable photothermal properties of Au NBPs@PDA resulted in the more efficient killing of cancer cells, demonstrating the great promise of the all-in-one nanoplatform for accurate diagnosis and tumor therapy.

Ratiometric Multicolor Analysis of Intracellular MicroRNA Using a Chain Hybrid Substitution-Triggered Self-Assembly of Silver Nanocluster-Based Label-Free Sensing Platform.

A simple and label-free sensing platform with low background based on the chain-displacement triggered self-assembly of Ag NCs was developed for ratiometric visual analysis of intracellular miRNA-21. Based on this sensitively ratiometric sensing approach, a picomole limit detection for miRNA-21 can be obtained. Most importantly, compared with the traditional single base mismatch detection method, our proposed method can realize single base mismatch detection according to the remarkable fluorescence color conversion, rather than simple fluorescence intensity change, which can obviously improve the accuracy and reliability. In addition, successful multicolor real-time monitoring of intracellular miRNA-21 makes the probe a potential candidate for miRNA-21 inhibiting drug screening. Furthermore, MCF-7, HeLa, and normal L02 cells can also be visually differentiated according to the fluorescence color by using the label-free sensing platform, showing its potential prospect in target visual analysis.

Ultrahighly Efficient and Stable Fluorescent Gold Nanoclusters Coated with Screened Peptides of Unique Sequences for Effective Protein and Serum Discrimination.

Gold nanoclusters (Au NCs) coated with various peptides have been widely used as fluorescent probes, and nowadays the most commonly used are cysteine (C) and tyrosine (Y) based ones. Herein, we report the preparation and clinical application of highly efficient and stable fluorescent Au NCs protected by screened peptides with a specific amino acid sequence Cys-Met-Met-Met-Met-Met (CMMMMM). Compared with traditional C, Y based peptide (CYYYYY) protected Au NCs, the fluorescence intensity of the CMMMMM-Au NCs increased by 230%, and the photobleaching resistance or stability of the CMMMMM-Au NCs increased by about 300% (after continuous ultraviolet irradiation for 60 min, the fluorescence of the CMMMMM-Au NCs remained more than 90% of their initial intensity, while the CYYYYY-Au NCs remained less than 30%). Assaying arrays based on CMMMMM protected Au NCs with different positive or negative charges as sensing receptors were developed through regulating different pH values, and multivariate analysis on the patterns obtained by these arrays allowed effective identification of not only ten proteins separately but also complex protein mixtures with subtly diverse compositions. The docking simulation and isothermal titration confirmed that target proteins interacted with CMMMMM-Au NCs mainly through electrostatic interactions and partly hydrophobic interactions, which affected the binding energy and fluorescence lifetime of CMMMMM-Au NCs, resulting in the unique fingerprint-like recognition patterns. Furthermore, serums from breast cancer, severe osteoarthritis, and rectal cancer patients can be effectively identified with healthy people using this CMMMMM-Au NCs based sensor array.

Ultrasensitive detection of prostate specific antigen using a personal glucose meter based on DNA-mediated immunoreaction.

With the increase in cancer risk, early immunodiagnosis is of great significance for timely therapy. In this work, a DNA-mediated immunosensor for the highly sensitive detection of prostate specific antigen (PSA) is proposed, which is mainly based on a portable personal glucose meter (PGM). Gold nanoparticles (AuNPs) functionalized with PSA detection antibodies and DNA primers are introduced. When the target of the PSA is present, rolling circle amplification (RCA) reactions on AuNPs are triggered and numerous repeated RCA products hybridize with the DNA-conjugated invertase; thus the signal of the PGM is generated and the PSA is quantified indirectly. With the use of a portable PGM, our method realizes a linear detection range of 0.003-50 ng mL-1, with a low detection limit of 0.1 pg mL-1, which is comparable to that of the traditional methods using expensive apparatus. Besides, the analysis of clinical human serum samples is performed to investigate its good practicability. This simple, low-cost, and miniaturized immunosensor is promising for the point-of-care testing of cancer markers.

Intracellular fluorometric determination of microRNA-21 by using a switch-on nanoprobe composed of carbon nanotubes and gold nanoclusters.

A sensitive and rapid fluorometric "switch on" assay is described for the detection of microRNA-21. It is based on the use of a fluorescence resonance energy transfer pair consisting of lysozyme-modified gold nanoclusters (Lys-Au NCs) and carbon nanotubes (CNTs). The Lys-Au NCs can be synthesized by a microwave-assisted technique within 2.5 min. They were modified with the ss-DNA probe (a 22-mer) for microRNA-21. Once the ss-DNA associates with the CNTs due to π stacking, the orange-red fluorescence (with excitation/emission peaks at 500/610 nm) is quenched. Nevertheless, the quenched fluorescence can be recovered after addition of microRNA-21 because of the stronger affnity between ss-DNA and microRNA-21. On the basis of the fluorescence recovery at 610 nm caused by microRNA-21, the latter can be quantified in the 0.01 to 100 nM concentration range, with a 36 pM detection limit. The method was applied to the determination of microRNA-21 in spiked serum with recoveries ranging from 98.6% to 110.0%. It also enables normal and cancer cells to be differentiated by direct imaging of intracellular microRNA-21. Graphical abstract A sensitive "switch on" FRET-based fluorometric assay for microRNA-21 is described. It is based on the use of  lysozyme-modified gold nanoclusters (Lys-Au NCs) and carbon nanotubes (CNTs) as energy donor and energy acceptor, respectively.

SERS-Based Pump-Free Microfluidic Chip for Highly Sensitive Immunoassay of Prostate-Specific Antigen Biomarkers.

Highly sensitive analysis of cancer biomarkers demonstrates an important impact in early diagnosis and therapies of cancer. A novel surface-enhanced Raman scattering (SERS) based immunoassay using microfluidic technique was reported for rapid analysis of prostate-specific antigen (PSA) biomarker. It is a useful screening test to discriminate prostate cancer and other diseases related to prostate. A "sandwich" immunoassay based on SERS nanotags, PSA biomarkers, and magnetic beads was applied on a pump-free microfluidic sensor. Magnetic immunocomplexes are isolated and trapped at the detection chamber by a permanent magnet integrated into the chip. The PBS buffer washed magnetic immunocomplexes and brought the free gold nanoparticles to the downsteam channel for waste. Our results show a good linear response in the range from 0.01 to 100 ng mL-1. The limit of detection of the PSA level is estimated to be below 0.01 ng mL-1 using this chip. This detection level of PSA biomarker in human serum can be accomplished in 5 min without manual incubation and a heavy syringe pump. To the best of our knowledge, this is the first SERS-based immunoassay which applied a pump-free microfluidic chip as a detection platform. We believe that the proposed method reveals a valuable potential tool for the diagnosis of prostate cancer.