Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (ß = 1400.230 mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (ß = -0.006 mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Metabolic engineering of Corynebacterium crenatum for enhanced L-tyrosine production from mannitol and glucose.

BACKGROUND: L-Tyrosine (L-Tyr) is a significant aromatic amino acid that is experiencing an increasing demand in the market due to its distinctive characteristics. Traditional production methods exhibit various limitations, prompting researchers to place greater emphasis on microbial synthesis as an alternative approach. RESULTS: Here, we developed a metabolic engineering-based method for efficient production of L-Tyr from Corynebacterium crenatum, including the elimination of competing pathways, the overexpression of aroB, aroD, and aroE, and the introduction of the mutated E. coli tyrAfbr gene for elevating L-Tyr generation. Moreover, the mtlR gene was knocked out, and the mtlD and pfkB genes were overexpressed, allowing C. crenatum to produce L-Tyr from mannitol. The L-Tyr production achieved 6.42 g/L at a glucose-to-mannitol ratio of 3:1 in a shake flask, which was 16.9% higher than that of glucose alone. Notably, the L-Tyr production of the fed-batch fermentation was elevated to 34.6 g/L, exhibiting the highest titers among those of C. glutamicum previously reported. CONCLUSION: The importance of this research is underscored by its pioneering application of mannitol as a carbon source for the biosynthesis of L-Tyr, as well as its examination of the influence of mannitol-associated genes in microbial metabolism. A promising platform is provided for the production of target compounds that does not compete with human food source.

Quantum dot bead-based competitive immunochromatographic assay for enterotoxin aureus A detection in pasteurized milk.

Staphylococcal enterotoxin A (SEA) is an important biotoxin, produced by Staphylococcus aureus under appropriate conditions, and often contaminates milk and dairy products. Herein, an anti-SEA monoclonal antibody (anti-SEA mAb) was prepared by injecting the SEA protein in BALB/c mice, and a novel immunochromatographic assay (ICA) was developed for the rapid and sensitive determination of SEA in pasteurized milk by using highly luminescent quantum dot beads (QB) as signal amplification probe. Given the 1020-fold enhancement in the photoluminescence intensity of QB to the original quantum dot, the proposed QB-ICA exhibits high sensitivity for SEA determination in real milk samples with a limit of detection of 1.89 ng/mL, and shows good dynamic linearity for SEA quantitative detection from 2 to 150 ng/mL within 15 min of test time. The proposed QB-ICA also shows good selectivity to SEA detection with a negligible cross-reaction to common analogs, including staphylococcal enterotoxins B, C, D, and E. In addition, the accuracy and precision of QB-ICA were assessed by analyzing SEA-fortified milk samples. The average recoveries of intra- and interassays range from 85.5 to 128.1%, and the coefficients of variation range from 4.6 to 14.2%, indicating an acceptable accuracy for the quantitative detection of SEA in real milk samples. In summary, this work provides a powerful and rapid analysis tool for the sensitive monitoring of SEA contamination in pasteurized milk samples.

A Universal Boronate-Affinity Crosslinking-Amplified Dynamic Light Scattering Immunoassay for Point-of-Care Glycoprotein Detection.

Herein, we report a universal boronate-affinity crosslinking-amplified dynamic light scattering (DLS) immunoassay for point-of-care (POC) glycoprotein detection in complex samples. This enhanced DLS immunoassay consists of two elements, i.e., antibody-coated magnetic nanoparticles (MNP@mAb) for target capture and DLS signal transduction, and phenylboronic acid-based boronate-affinity materials as crosslinking amplifiers. Upon the addition of targets, glycoproteins are first captured by MNP@mAb and amplified by target-induced crosslinking stemming from the selective binding between the boronic acid ligand and cis-diol-containing glycoprotein, thereby resulting in a remarkably increased DLS signal in the average nanoparticle size. Benefiting from the multivalent binding and fast boronate-affinity reaction between glycoproteins and crosslinkers, the proposed immunosensing strategy has achieved the ultrasensitive and rapid quantitative assay of glycoproteins at the fM level within 15 min. Overall, this work provides a promising and versatile design strategy for extending the DLS technique to detect glycoproteins even in the field or at POC.

Quantum bead-based fluorescence-linked immunosorbent assay for ultrasensitive detection of aflatoxin M1 in pasteurized milk, yogurt, and milk powder.

Herein, we reported a novel direct competitive fluorescence-linked immunosorbent assay (dcFLISA) for the ultrasensitive detection of aflatoxin M1 (AFM1) in pasteurized milk, yogurt, and milk powder using 150-nm quantum dot beads (QB) as the carrier of competing antigen. Large QB were applied to decrease the binding affinity of the competing antigen to antibody and enhance the fluorescent signal intensity. The aflatoxin B1 molecule was used as the surrogate of AFM1 to label with BSA on the surface of QB because of its 63% cross reaction to anti-AFM1 mAb. The binding affinity of the competing antigen to mAb was tuned by changing the labeled molar ratios of aflatoxin B1 to BSA. Through combining the advantages of QB as the carrier of the competing antigen, including low binding affinity to mAb and highly fluorescent signal output, the proposed dcFLISA exhibited an ultrahigh sensitivity for AFM1 detection, with a half-maximal inhibitory concentration of 3.15 pg/mL in 0.01 M phosphate-buffered saline solution (pH 7.4), which is substantially lower than that of the traditional horseradish peroxidase-based ELISA. The proposed method also exhibited very low detection limitations of 0.5, 0.6, and 0.72 pg/mL for real pasteurized milk, yogurt, and milk powder, respectively. These values are considerably below the maximum permissible level of the European Commission standard for AFM1 in dairy products. In summary, the proposed dcFLISA offers a novel strategy with an ultrahigh sensitivity for the routine monitoring of AFM1 in various dairy products.

Naked-eye sensitive detection of nanoPET by pH-responsive colorimetric method based on dual-enzyme catalysis.

A pH-responsive colorimetric method based on dual-enzyme catalysis for rapid and facile detection and quantification of nanoPET at environment-dependent concentration is proposed. The nanoPET was hydrolyzed by the synergistic catalysis of cutinase and lipase to terephthalic acid which can be sensitive detected using bromocresol purple as the indicator. The color changed from purple to bright yellow as the nanoPET detection concentration increased from 0 mg/mL to 2 mg/mL which can be detected by UV-Vis. This naked-eye method has a high sensitivity for nanoPET detection with the visual detection cutoff of 31.00 µg/mL, and has a good linearity in the range of 0 âˆ¼ 1 mg/mL with LOD of 22.84 µg/mL. The reliability of this method is verified in the detection of nanoPET in lake water and beer samples, with an average recovery of 87.1 %. The as-developed dual-enzyme colorimetric chemosensor holds promising potential as a robust and effective platform for the sensitive detection of nanoPET.

Role of extracellular polymeric substances in the aggregation and biological response of micro(nano)plastics with different functional groups and sizes.

In this work, the effects of extracellular polymeric substances (EPS) on the aggregation and biological responses of different micro(nano)plastics (MNPs, <1000 µm) were investigated. EPS increased the colloidal stability of PS MPs in NaCl or CaCl2. For the three PS NPs (PS-NH2, PS-COOH, and PS-naked), EPS also enhanced their colloidal stabilities in the presence of NaCl. However, the effect of CaCl2 on the colloidal stabilities of PS NPs in the presence of EPS depended on their surface functional groups. In CaCl2, both Derjaguin-Landau-Verwey-Overbeek theory and molecular bridging explained the interaction between MNPs (both NPs and MPs) and EPS. Laser Direct Infrared and scanning electron microscope imaging showed that opalescent EPS corona formed on PS MPs via intermolecular-bridging by Ca2+, and the critical coagulation concentrations (70 mM in NaCl, 1.5 mM in CaCl2) in EPS were much lower than that for PS NPs (1000 mM for NaCl; 65 mM for CaCl2). PS-NH2 NPs showed the highest increase in the growth of bacteria (Bacillus subtilis), followed by PS MPs and PS-naked NPs, while PS-COOH NPs had no significant effect. Biological response of PS NPs was unaffected by EPS, while EPS further enhanced the positive effects of PS MPs on bacterial growth.

Rapid and sensitive determination of lactoferrin in milk powder by boronate affinity amplified dynamic light scattering immunosensor.

Lactoferrin (Lf) is a bioactive multifunctional glycoprotein that belongs to the transferrin family. As an important nutritional fortifier, Lf is one of the star nutrients in milk powder. Thus, the rapid and accurate quantitative detection of Lf content in milk powder is crucial to the evaluation of its quality. However, most reported immunoassay methods for Lf quantitation suffer from cumbersome sample pretreatment or lengthy testing time and do not meet the requirements for rapid Lf detection in milk powder. Herein, we report a novel method combining dynamic light scattering (DLS) immunosensing and boronate affinity recognition for the rapid and sensitive detection of Lf. Owing to the selective binding between a boronate ligand and the cis diol, the developed DLS immunosensor quantitatively detected Lf with saving one antibody, greatly reducing the need for matching antibodies, which are needed in traditional sandwich immunoassay for biomolecular detection. In addition, the DLS immunosensor exhibited high selectivity and sensitivity to Lf, with a detection limit of 1 ng/mL within ∼15 min through coupling with magnetic nanoparticle-assisted immunomagnetic separation and DLS signal transduction.

Perceived stress and mobile phone addiction among college students: The roles of self-control and security.

Objective: According to the General Strain Theory, stress can lead to a range of problem behaviors. In the current study, we focused on the association between perceived stress and mobile phone addiction. We hypothesized that this association is mediated by low self-control and that the first path of the mediation is moderated by security. Methods: College students (N = 397; ages 16-21; 51.89% females) from a university in Hunan Province, China, were surveyed by cluster sampling method. The students completed the Smartphone Addiction Scale-Short Version (SAS-SV), the Depression Anxiety Stress Scale (DASS-21), the Self-Control Scale (SCS), and the Security Questionnaire (SQ) during regular class time. SPSS26.0 statistical software was used for descriptive statistics and Pearson correlation analyses, the SPSS macro PROCESS was used to test the mediating effects of self-control and the moderating role of security. Results: Mediation analysis showed that as expected, perceived stress was associated with lower self-control, which in turn was associated with a higher risk for mobile phone addiction. Also as expected, moderated mediation analysis indicated that the association between perceived stress and self-control was moderated by security. Specifically, the relationship between perceived stress and self-control was stronger for low security. Conclusion: This study provides useful insight into the understanding of how perceived stress increases the risk of mobile phone addiction. The results are consistent with the General Strain Theory and further indicate that concrete approaches are required for the prevention and intervention to reduce mobile phone addiction among college students.

Low-sample-consumption and ultrasensitive detection of procalcitonin by boronate affinity recognition-enhanced dynamic light scattering biosensor.

Accurate determination of procalcitonin (PCT) is highly crucial in bacterial infection diagnosis. Many biosensors previously developed suffer from large sample consumption or lengthy waiting time, which raise difficulties for more vulnerable patients, such as infants, old people, and other critically ill patients. To address this dilemma, we present an innovative boronate affinity recognition (BAR)-enhanced dynamic light scattering (DLS) biosensor to achieve ultrasensitive PCT detection. In this biosensing system, monoclonal antibody-modified magnetic nanoparticles (MNP@mAb) are designed as probes to capture PCT from serum samples and generate DLS signal transduction. Polyvalent phenylboronic acid-labeled bovine serum albumin (BSA@PBA) is used as scaffold to aggregate MNP@mAb and PCT (MNP@mAb-PCT) complex because of the specific interaction of cis-diol-containing PCT with boronic acid ligands on the surface of BSA@PBA. The BAR-enhanced DLS biosensor shows ultrahigh sensitivity to PCT determination due to high binding affinity, with the limit of detection of 0.03 pg/mL. The total detection time of PCT in whole blood or serum is less than 15 min with small sample consumption (about 1 µL) due to the rapid magnetic separation and aggregation of MNP@mAb-PCT triggered by BSA@PBA. In addition, the proposed DLS biosensor exhibits a high specificity for PCT quantitative detection. Therefore, this work provides a promising and versatile strategy for extending DLS biosensor to rapid and ultrasensitive detection of trace PCT for broader patients and more urgent cases.

M13 bacteriophage as biometric component for orderly assembly of dynamic light scattering immunosensor.

The ordered assembly of nanostructure is an effective strategy used to manipulate the hydrodynamic diameter (DH) of nanoparticles. Herein, a versatile dynamic light scattering (DLS) immunosensing platform is presented to sensitively detect small molecules and biomacromolecules by using the M13 phage as the building module to order the assembly of gold nanoflowers and gold-coated magnetic nanoparticles, respectively. After the directional assembly of M13 phage, the DH of the probes was significantly increased due to its larger filamentous structure, thus improving the detection sensitivity of the DLS immunosensor. The designed M13 assembled DLS immunosensor with competitive and sandwich formats showed high sensitivities for ochratoxin A and alpha-fetoprotein in real corn and undiluted serum samples, with the detection limits of 1.37 and 57 pg/mL, respectively. These values are approximately 15.8 and 164.9 times lower than those of traditional phage-based enzyme-linked immunosorbent assays. Collectively, this work provides a promising strategy to manipulate the DH of nanoparticles by highly evolved biomaterials such as engineered M13 phages and opens upon a new direction for developing DLS immunosensors to detect various targets by the fusion expression of special peptide or nanobody on the pIII or pVIII protein of M13 phage.

Smartphone Addiction and Eysenck's Personality Traits Among Chinese Adolescents: A Meta-Analysis.

With the quickly rising popularity of smartphone among adolescents over the past decade, studies have begun to investigate the relationship between smartphone addiction and Eysenck's personality traits. Despite numerous studies on this topic, however, findings have been mixed and there is a lack of consensus regarding this relationship. Thus, this meta-analysis aimed to explore the relationship between smartphone addiction and Eysenck's personality traits in Chinese adolescents, as well as its possible moderators. Through literature search and screening, 33 studies were included, comprising 79 independent effect sizes with a total of 17, 737 subjects. A random effects model was selected, and it was found that smartphone addiction was positively associated with psychoticism (r = 0.16, p < 0.001) and neuroticism (r = 0.32, p < 0.001), but not significantly associated with extroversion (r = -0.06, p = 0.079). The moderating effect test showed that sex and year of study publication had significant influences on the relationship between smartphone addiction and psychoticism, and the year of study publication had a significant influence on the relationship between smartphone addiction and neuroticism. This study is the first meta-analysis on the relationship between smartphone addiction and Eysenck's personality traits among adolescents in China, and the results have helped to clarify the controversy of previous studies regarding this relationship.

Formation of silver nanoparticles in aquatic environments facilitated by algal extracellular polymeric substances: Importance of chloride ions and light.

Natural conversion of metal species is an important source for nanoscale metal particles in the aquatic environment, and it could affect their fate and toxicity. Extracellular polymeric substances (EPSs) are ubiquitous and abundant in the aquatic environment, thus likely can reduce metal ions to nanoscale particles. However, the effect of natural inorganic ligand and light on this process has not been well investigated. In this work, Ag+ was readily reduced to silver nanoparticles (AgNPs, around 15 nm in size) by the EPS collected from Chlorella pyrenoidosa. AgNPs could be generated in the dark environment but at a slow rate. Visible light accelerated the photoreduction. The reaction mechanism probed by Fourier transform infrared spectroscopy and three-dimensional excitation-emission matrix spectrometry demonstrated that the reduction in Ag+ was attributed to the protein and polysaccharides in the EPS. The presence of chloride ions (Cl-) largely shortened the duration of photoreduction. Scanning electron microscopy results indicated that with the aid of EPS, the AgCl nanocrystal was converted to core-shell structure, with dot-like nano Ag acting as the shell and the AgCl nanocrystal acting as the core. Size and morphological changes were observed on transmission electron microscopy. This study adds new knowledge of the joint effect of light exposure, Cl-, and EPS on the formation of AgNPs from Ag+ and advances the understanding of the natural formation mechanism of AgNPs.

Dual-mode fluorescent and colorimetric immunoassay for the ultrasensitive detection of alpha-fetoprotein in serum samples.

We present a novel dual-mode fluorescent and colorimetric immunosensor based on conventional immunoassay platforms by utilizing a gold nanoflower (AuNF)-loaded fluorescein molecule (AuNF@Fluorescein) as signal output. The AuNFs were modified with thiolated carboxyl ligand, which consisted of a hydrophobic alkane chain as hydrophobic wallet for fluorescein encapsulation, a tetra (ethylene glycol) unit for biocompatibility and solubility, and a functional carboxyl group for the conjugation of biorecognition molecules for biosensing. The resultant AuNFs showed a high loading capacity of 3.74 × 106 fluorescein molecules per AuNF because of its flower-like shape with many complex branches. By adjusting the solution pH to 8.0, the fluorescein molecules can almost entirely be released from the hydrophobic wallet of AuNF@Fluorescein, which led to strong fluorescent-signal amplification. Under the optimal detection conditions, the proposed immunoassay based on fluorescent signal exhibited ultrahigh sensitivity for alpha-fetoprotein (AFP) detection, with a limit of detection (LOD) of 29 fg/mL. This value is approximately 9.3 × 103-fold lower than that of corresponding horseradish peroxidase (HRP)-based immunoassay (LOD = 270 pg/mL). The fluorescein molecule also had intrinsic peroxidase-like activity to catalyze 3,3',5,5'-tetramethylbenzidine oxidation with hydrogen peroxide for colorimetric signal. The proposed method with colorimetric mode further exhibited a sensitivity with a LOD of 17.7 pg/mL, which is about 15-fold lower than that of conventional HRP-based immunoassay. The recoveries of the proposed dual-mode immunoassay for AFP spiked serum samples ranged within 89.85%-100.0%, with the coefficient of variations ranging from 0.5% to 2.4%, indicating acceptable accuracy and precision for AFP quantitative detection. The reliability of the developed dual-mode immunoassay was further compared with a commercial chemiluminescence immunoassay kit by analyzing 20 clinical serum samples, showing that the two methods well agreed with each other, with high correlation coefficients of 0.997 and 0.986 based on recorded fluorescence and colorimetric signals, respectively. In summary, the proposed method was highly suitable for the ultrasensitive analysis of biomarkers or infectious diseases by fluorescence mode and can be used for routine clinical diagnosis by colorimetric mode.

Ultrasensitive direct competitive FLISA using highly luminescent quantum dot beads for tuning affinity of competing antigens to antibodies.

Herein, for the first time we report a novel direct competitive fluorescence-linked immunosorbent assay (dcFLISA) for the ultrasensitive detection of ochratoxin A (OTA) by introducing a large size polymer beads loaded with quantum dots (QBs) as carrier of competing antigen for decreasing binding affinity to antibody and enhancing the fluorescent signal intensity. When using 255 nm QBs as carrier of competing antigen, the equilibrium dissociation constant of QB based competing antigen to antibodies can be tuned to 100 times higher than that of the horseradish peroxidase (HRP) based competing antigen by controlling labeled amounts of antigen on the surface of QBs. Various parameters that influenced the sensitivity of dcFLISA were investigated and optimized. Under optimum detection parameters, the dynamic linear range of developed dcFLISA for detecting OTA was established at 0.05 pg/mL to 1.56 pg/mL with a half maximal inhibitory concentration at 0.14 ± 0.04 pg/mL (n = 5), which is three orders of magnitude lower than that of conventional HRP-based dcELISA (0.24 ng/mL). The developed FLISA is also highly accurate, reliable, and shows no cross reaction to other mycotoxins. In summary, the proposed method offers a straightforward approach to improve the sensitivity of direct competitive immunoassay for trace small chemical molecule detection in food quality control, environmental monitoring, and clinical diagnosis.