Advances in biosensors for major depressive disorder diagnostic biomarkers.

Depression is one of the most common mental disorders and is mainly characterized by low mood or lack of interest and pleasure. It can be accompanied by varying degrees of cognitive and behavioral changes and may lead to suicide risk in severe cases. Due to the subjectivity of diagnostic methods and the complexity of patients' conditions, the diagnosis of major depressive disorder (MDD) has always been a difficult problem in psychiatry. With the discovery of more diagnostic biomarkers associated with MDD in recent years, especially emerging non-coding RNAs (ncRNAs), it is possible to quantify the condition of patients with mental illness based on biomarker levels. Point-of-care biosensors have emerged due to their advantages of convenient sampling, rapid detection, miniaturization, and portability. After summarizing the pathogenesis of MDD, representative biomarkers, including proteins, hormones, and RNAs, are discussed. Furthermore, we analyzed recent advances in biosensors for detecting various types of biomarkers of MDD, highlighting representative electrochemical sensors. Future trends in terms of new biomarkers, new sample processing methods, and new detection modalities are expected to provide a complete reference for psychiatrists and biomedical engineers.

Dynamic Monitoring of Biomolecular Hydrodynamic Dimensions by Magnetization Motion on Quartz Crystal Microbalance.

Hydrodynamic dimension (HD) is the primary indicator of the size of bioconjugated particles and biomolecules. It is an important parameter in the study of solid-liquid two-phase dynamics. HD dynamic monitoring is crucial for precise and customized medical research as it enables the investigation of the continuous changes in the physicochemical characteristics of biomolecules in response to external stimuli. However, current HD measurements based on Brownian motion, such as dynamic light scattering (DLS), are inadequate for meeting the polydisperse sample demands of dynamic monitoring. In this paper, we propose MMQCM method samples of various types and HD dynamic monitoring. An alternating magnetic field of frequency ωm excites biomolecule-magnetic bead particles (bioMBs) to generate magnetization motion, and the quartz crystal microbalance (QCM) senses this motion to provide HD dynamic monitoring. Specifically, the magnetization motion is modulated onto the thickness-shear oscillation of the QCM at the frequency ωq. By analysis of the frequency spectrum of the QCM output signal, the ratio of the magnitudes of the real and imaginary parts of the components at frequency ωq ± 2ωm is extracted to characterize the particle size. Using the MMQCM approach, we successfully evaluated the size of bioMBs with different biomolecule concentrations. The 30 min HD dynamic monitoring was implemented. An increase of ∼10 nm in size was observed upon biomolecular structural stretching. Subsequently, the size of bioMBs gradually reduced due to the continuous dissociation of biomolecules, with a total reduction of 20∼40 nm. This HD dynamic monitoring demonstrates that the release of biomolecules can be regulated by controlling the duration of magnetic stimulation, providing valuable insights and guidance for controlled drug release in personalized precision medicine.

Near-freezing temperature suppresses avocado (Persea americana Mill.) fruit softening and chilling injury by maintaining cell wall and reactive oxygen species metabolism during storage.

To enhance the postharvest quality of avocado (Persea americana Mill.) fruit, this study investigates alterations in cell wall metabolism and reactive oxygen species (ROS) metabolism during near-freezing temperature (NFT) storage, and explores their impact on fruit softening. The fruit was stored at 25 °C, 5 °C, 2 °C, and NFT, respectively. NFT storage retarded firmness loss and chilling injury in comparison with 25 °C, 5 °C, and 2 °C. NFT storage delayed the decrease of ionic-soluble pectin (ISP) and cellulose (CLL) contents by suppressing cell wall degradation enzyme activities. Correlation analysis showed that cell wall degradation enzyme activities were positively correlated to rates of ethylene release and respiration. Moreover, NFT storage maintained higher levels of DPPH and ABTS scavenging abilities, activities of superoxide dismutase, peroxidase, and catalase, as well as ascorbate-glutathione cycle (ascorbic acid, glutathione, glutathione disulfide, ascorbate peroxidase, cycle-related enzymes), thereby inhibited the increase of ROS content, malondialdehyde content, and cell membrane permeability. Fruit firmness and chilling injury were correlated with the contents of hydrogen (H2O2), superoxide anion (O2.-), ISP, and CLL. These results suggested that NFT could suppress fruit softening and chilling injury by inhibiting cell wall degradation through delaying respiration and ethylene production and suppressing ROS production via activation of antioxidant systems, thereby maintaining quality and prolonged storage life during avocado fruit storage.

Spatiotemporal variation, fluxes and risk evaluation of neonicotinoid insecticides within the midsection of Yangtze River, China: An exploration as ecological protection threshold.

Neonicotinoid insecticides (NNIs) have attracted global concern due to its extensive use in agricultural activities and their potential risks to the animal and human health, however, there is limited knowledge on the regional traits and ecological risks of NNIs in the aquatic environments. We herein investigated the occurrence of NNIs within the midsection of Yangtze River in China, offering the inaugural comprehensive report on NNIs within this region. In this study, eleven NNIs were analyzed in 108 river water and sediment samples from three seasons (normal, dry and wet season). We detected a minimum of seven NNIs in the water and four NNIs in the sediment, with total concentrations ranging from 12.33 to 100.5 ng/L in water and 0.08-5.68 ng/g in sediment. The levels of NNIs in both river water and sediment were primarily influenced by the extent of agricultural activities. The estimated annual load of NNIs within the midsection of Yangtze River totaled 40.27 tons, April was a critical contamination period. Relative potency factor (RPF) analysis of the human exposure risk revealed that infants faced the greatest exposure risk, with an estimated daily intake of 11.27 ng kg-1∙bw∙d-1. We established the acute and chronic thresholds for aquatic organisms by employing the Species Sensitive Distribution (SSD) method (acute: 384.1 ng/L; chronic: 168.9 ng/L). Based on the findings from this study, 33% of the river water samples exceeded the chronic ecological risks thresholds, indicating the urgent need for intervention programs to guarantee the safety of the river for aquatic life in the Yangtze River Basin.

Proximity proteomics reveals UCH-L1 as an essential regulator of NLRP3-mediated IL-1ß production in human macrophages and microglia.

Activation of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome complex is an essential innate immune signaling mechanism. To reveal how human NLRP3 inflammasome assembly and activation are controlled, in particular by components of the ubiquitin system, proximity labeling, affinity purification, and RNAi screening approaches were performed. Our study provides an intricate time-resolved molecular map of different phases of NLRP3 inflammasome activation. Also, we show that ubiquitin C-terminal hydrolase 1 (UCH-L1) interacts with the NACHT domain of NLRP3. Downregulation of UCH-L1 decreases pro-interleukin-1ß (IL-1ß) levels. UCH-L1 chemical inhibition with small molecules interfered with NLRP3 puncta formation and ASC oligomerization, leading to altered IL-1ß cleavage and secretion, particularly in microglia cells, which exhibited elevated UCH-L1 expression as compared to monocytes/macrophages. Altogether, we profiled NLRP3 inflammasome activation dynamics and highlight UCH-L1 as an important modulator of NLRP3-mediated IL-1ß production, suggesting that a pharmacological inhibitor of UCH-L1 may decrease inflammation-associated pathologies.

Advances in heart failure monitoring: Biosensors targeting molecular markers in peripheral bio-fluids.

Cardiovascular diseases (CVDs), especially chronic heart failure, threaten many patients' lives worldwide. Because of its slow course and complex causes, its clinical screening, diagnosis, and prognosis are essential challenges. Clinical biomarkers and biosensor technologies can rapidly screen and diagnose. Multiple types of biomarkers are employed for screening purposes, precise diagnosis, and treatment follow-up. This article provides an up-to-date overview of the biomarkers associated with the six main heart failure etiology pathways. Plasma natriuretic peptides (BNP and NT-proBNP) and cardiac troponins (cTnT, cTnl) are still analyzed as gold-standard markers for heart failure. Other complementary biomarkers include growth differentiation factor 15 (GDF-15), circulating Galactose Lectin 3 (Gal-3), soluble interleukin (sST2), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). For these biomarkers, the electrochemical biosensors have exhibited sufficient sensitivity, detection limit, and specificity. This review systematically summarizes the latest molecular biomarkers and sensors for heart failure, which will provide comprehensive and cutting-edge authoritative scientific information for biomedical and electronic-sensing researchers in the field of heart failure, as well as patients. In addition, our proposed future outlook may provide new research ideas for researchers.

Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage.

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.

Impact of CYP2A6 Gene Polymorphism on the Efficacy and Safety of S-1 Therapy in Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: The relationship of CYP2A6 polymorphisms with S-1 therapy outcomes in gastric cancer is unclear. This review aims to assess the association between CYP2A6 gene polymorphisms (CYP2A6*4, *7, *9, *10) and S-1 therapy outcomes in gastric cancer, aiming to identify predictive markers for S-1 efficacy and adverse reactions. METHODS: We searched seven databases, using random or fixed effect models to calculate hazard ratio (HR) and 95% confidence interval (CI) based on study heterogeneity. RESULTS: A total of 1143 articles were retrieved from multiple online databases as of March 28, 2023. After screening, seven articles containing seven investigations were included in the meta-analysis. Our results revealed a significant association between the CYP2A6 polymorphism site and the overall survival (OS) of V/V patients compared to W/W or W/V patients (HR=2.73, 95%CI:1.45-5.14, P=0.002). S-1 was more beneficial for W/W or W/V patients than V/V patients in terms of Progression-Free Survival (PFS) (HR=3.15,95%CI:1.47-6.75, P=0.003). There was no association between CYP2A6 polymorphism and hematological adverse reactions (OR=0.52, 95%CI: 0.23-1.15, P=0.104). CONCLUSION: CYP2A6 polymorphisms correlate with S-1 efficacy (OS, PFS) in gastric cancer, suggesting their potential as predictive markers. However, the generalizability of findings is limited by the small number of studies from Eastern countries and variations in chemotherapy regimens and detection methods. Further large-scale studies are needed to confirm these associations.

High-Resolution Lipidomics Reveals Influence of Biomass and Pretreatment Process on the Composition of Extracted Algae Oils As Feedstock for Sustainable Aviation Fuels.

The increasing demand for sustainable aviation fuel (SAF) creates a need for innovative biomass and lipid sources with compositions that are compatible with refineries. Algae-derived oils present an opportunity to supply a process-compatible lipid feedstock at yields higher than those of conventional oilseed crops. With few documented reports on chemical composition, the process readiness remains elusive. We present data on extraction efficiency, yield, and purity of lipids from algae with and without the application of a low-concentration sulfuric acid pretreatment of the biomass. The pretreatment process increased the oil yield and positively impacted the quality of the extracted oils. Results from fatty acid and lipidomics analysis revealed that the low-lipid biomass sources extracted 70-80% of the available lipids, and the non-fatty acid co-extractants exceeded 40% of the extracted oils. For a high-lipid algae sample, derived from a genetically engineered strain, we show >90% extraction yield with >85% FAME purity. This work provides insights into the composition of algae-derived oils and quality metrics that are essential to determining the viability of lipid hydroprocessing to SAF.

Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.

Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.

FBXO22 promotes glioblastoma malignant progression by mediating VHL ubiquitination and degradation.

Glioblastoma (GBM) is the most common malignant primary brain tumor. Despite comprehensive treatment with traditional surgery, radiotherapy, and chemotherapy, the median survival rate is <14.6% and the 5-year survival rate is only 5%. FBXO22, a substrate receptor of the SCF ubiquitin ligases, has been reported to play a promoting role in melanoma, liver cancer, cervical cancer, and other cancers. However, the function of FBXO22 in GBM has not been reported. In the present study, we demonstrate that FBXO22 is highly expressed in glioma and is positively correlated with worse pathological features and shorter survival of GBM patients. We revealed that FBXO22 promotes GBM cell proliferation, angiogenesis, migration, and tumorigenesis in vitro and in vivo. In terms of mechanism, we reveal that FBXO22 decreases VHL expression by directly mediating VHL ubiquitination degradation, which ultimately increases HIF-1α and VEGFA expression. In addition, our data confirm that there are positive correlations among FBXO22, HIF-1α, and VEGFA expression, and there is a negative correlation between FBXO22 and VHL protein expression in glioma patients. Our study strongly indicates that FBXO22 is a promising diagnostic marker and therapeutic target for glioma patients.

Selected legacy and emerging organic contaminants in sediments of China's Yangtze - the world's third longest river: Response to anthropogenic activities.

To explore contaminant concerns as a result of anthropogenic disturbance of the river system, this study provided the first extensive investigation of the contamination profiles, possible driving factors, and ecological risks of 40 target compounds including pharmaceuticals and personal care products (PPCPs), neonicotinoid pesticides (NNIs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) in sediments of the whole Yangtze River (the world's third longest river). Among these target compounds, PPCPs were the dominant contaminants with a total concentration (∑15PPCPs) of 2.13-14.99 ng/g, followed by ∑7PCBs (

Dynamical interplay between superconductivity and pseudogap in cuprates as revealed by terahertz third-harmonic generation spectroscopy.

We report on nonlinear terahertz third-harmonic generation (THG) measurements on YBa2Cu3O6+x thin films. Different from conventional superconductors, the THG signal starts to appear in the normal state, which is consistent with the crossover temperature T* of pseudogap over broad doping levels. Upon lowering the temperature, the THG signal shows an anomaly just below Tc in the optimally doped sample. Notably, we observe a beat pattern directly in the measured real-time waveform of the THG signal. We elaborate that the Higgs mode, which develops below Tc, couples to the mode already developed below T*, resulting in an energy level splitting. However, this coupling effect is not evident in underdoped samples. We explore different potential explanations for the observed phenomena. Our research offers valuable insight into the interplay between superconductivity and pseudogap.

The "Microplastome" - A Holistic Perspective to Capture the Real-World Ecology of Microplastics.

Microplastic pollution, an emerging pollution issue, has become a significant environmental concern globally due to its ubiquitous, persistent, complex, toxic, and ever-increasing nature. As a multifaceted and diverse suite of small plastic particles with different physicochemical properties and associated matters such as absorbed chemicals and microbes, future research on microplastics will need to comprehensively consider their multidimensional attributes. Here, we introduce a novel, conceptual framework of the "microplastome", defined as the entirety of various plastic particles (<5 mm), and their associated matters such as chemicals and microbes, found within a sample and its overall environmental and toxicological impacts. As a novel concept, this paper aims to emphasize and call for a collective quantification and characterization of microplastics and for a more holistic understanding regarding the differences, connections, and effects of microplastics in different biotic and abiotic ecosystem compartments. Deriving from this lens, we present our insights and prospective trajectories for characterization, risk assessment, and source apportionment of microplastics. We hope this new paradigm can guide and propel microplastic research toward a more holistic era and contribute to an informed strategy for combating this globally important environmental pollution issue.

Filamentous prophage Pf4 promotes genetic exchange in Pseudomonas aeruginosa.

Filamentous prophages are widespread among bacteria and play crucial functions in virulence, antibiotic resistance, and biofilm structures. The filamentous Pf4 particles, extruded by an important pathogen Pseudomonas aeruginosa, can protect producing cells from adverse conditions. Contrary to the conventional belief that the Pf4-encoding cells resist reinfection, we herein report that the Pf4 prophage is reciprocally and commonly exchanged within P. aeruginosa colonies, which can repair defective Pf4 within the community. By labeling the Pf4 locus with antibiotic resistance and fluorescence markers, we demonstrate that the Pf4 locus is frequently exchanged within colony biofilms, in artificial sputum media, and in infected mouse lungs. We further show that Pf4 trafficking is a rapid process and capable of rescuing Pf4-defective mutants. The Pf4 phage is highly adaptable and can package additional DNA doubling its genome size. We also report that two clinical P. aeruginosa isolates are susceptible to the Pf4-mediated exchange, and the Pf5 prophage can be exchanged between cells as well. These findings suggest that the genetic exchanging interactions by filamentous prophages may facilitate defect rescue and the sharing of prophage-dependent benefits and costs within the P. aeruginosa community.

Nanotoxicity of tungsten trioxide nanosheets containing oxygen vacancy to human umbilical vein endothelial cells.

Because of the excellent performance in photochemistry, WO3 is increasingly applied in the field of biology and medicine. However, little is known about the mechanism of WO3 cytotoxicity. In this work, WO3 nanosheets with oxygen vacancy are synthesized by solvothermal method, then characterized and added to culture medium of human umbilical vein endothelial cells (HUVECs) with different concentrations. We characterized and analyzed the morphology of nano-WO3 by transmission electron microscopy and calculated the specific data of oxygen vacancy by XPS. It is the first time the effect of WO3-x on cells that WO3-x can cause oxidative stress in HUVEC cells, resulting in DNA damage and thus promoting apoptosis. Transcriptome sequencing is performed on cells treated with low and high concentrations of WO3-x, and a series of key signals affecting cell proliferation and apoptosis are detected in differentially expressed genes, which indicates the research direction of nanotoxicity. The expression levels of key genes are also verified by quantitative PCR after cell treatment with different concentrations of WO3-x. This work fills the gap between the biocompatibility of nano WO3-x materials and molecular cytology and paves the way for investigating the mechanism and risks of oxygen vacancy in cancer therapy.

Surface Oxygen Deficiency Enabled Spontaneous Antiprotein Fouling in WO3 Nanosheets for Biosensing in Biological Fluids.

Biofouling deteriorates the performance of sensors operated in biofluids. Protein adsorption is believed to be the first step of biofouling, which also reduces biocompatibility by further inducing cell adhesion, platelet activation, and even inflammation. Current studies of antifouling coatings are focused on polymers and hydrogels, which have succeeded in remaining resistant to protein adsorption, but their application on sensor electrodes is limited due to low conductivity and biocompatibility. Here, we report a spontaneous antibiofouling strategy for sensor electrodes by controlling oxygen vacancies in WO3 nanosheets. Irreversible adsorption of proteins was reduced by 76% in unprocessed human plasma when electrodes were coated with WO3 rich in surface oxygen vacancy. These electrodes maintained 91% of the initial current density after 1 month of incubation in human plasma.

Efficacy and safety of fluticasone propionate/salmeterol and fluticasone propionate monotherapy in step-up treatment of childhood asthma: A systematic review and meta-analysis.

BACKGROUND: Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited. OBJECTIVE: This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment. METHODS: Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies. RESULTS: Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events. CONCLUSION: Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment.