Chronopotentiometric sensors for antimicrobial peptide-based biosensing of Staphylococcus aureus.

Charged antimicrobial peptides can be used for direct potentiometric biosensing, but have never been explored. We report here a galvanostatically-controlled potentiometric sensor for antimicrobial peptide-based biosensing. Solid-state pulsed galvanostatic sensors that showed excellent stability under continuous galvanostatic polarization were prepared by utilizing reduced graphene oxide/poly (3,4-ethylenedioxythiophene): poly (4-styrenesulfonate) (rGO/PEDOT: PSS) as a solid contact. More importantly, the chronopotentiometric sensor can be made sensitive to antimicrobial peptides with intrinsic charge on demand via a current pulse. In this study, a positively charged antimicrobial peptide that can bind to Staphylococcus aureus with high affinity and good selectivity was designed as a model. Two arginine residues with positive charges were linked to the C-terminal of the peptide sequence to increase its potentiometric responses on the electrode. The bacteria binding-induced charge or charge density change of the antimicrobial peptide enables the direct chronopotentiometric detection of the target. Under the optimized conditions, the concentration of Staphylococcus aureus can be determined in the linear range 10-1.0 × 105 CFU mL-1 with a detection limit of 10 CFU mL-1. It is anticipated that such a chronopotentiometric sensing platform is readily adaptable to detect other bacteria by choosing the peptides.

Generation of an iPSC line from a 79-year-old female patient diagnosed with sporadic Parkinson's disease.

Parkinson's disease is a common neurodegenerative disorder. Here we present a human induced pluripotent stem cells (iPSCs) derived from peripheral blood mononuclear cells (PBMCs) of a 79-year-old female patient diagnosed with sporadic Parkinson's disease using the sendai virus. Generated iPSCs maintain normal karyotype, exhibit pluripotent stem cell markers, and possess differentiation potential. The iPSCs allows for differentiation into various cell subtypes, providing conditions for the research of the pathogenesis and drug development of Parkinson's disease.

Oceanobacillus picturae alleviates cadmium stress and promotes growth in soybean seedlings.

Cadmium (Cd) is a heavy metal that significantly impacts human health and the environment. Microorganisms play a crucial role in reducing heavy metal stress in plants; however, the mechanisms by which microorganisms enhance plant tolerance to Cd stress and the interplay between plants and microorganisms under such stress remain unclear. In this study, Oceanobacillus picturae (O. picturae) was isolated for interaction with soybean seedlings under Cd stress. Results indicated that Cd treatment alone markedly inhibited soybean seedling growth. Conversely, inoculation with O. picturae significantly improved growth indices such as plant height, root length, and fresh weight, while also promoting recovery in soil physiological indicators and pH. Metabolomic and transcriptomic analyses identified 157 genes related to aspartic acid, cysteine, and flavonoid biosynthesis pathways. Sixty-three microbial species were significantly associated with metabolites in these pathways, including pathogenic, adversity-resistant, and bioconductive bacteria. This research experimentally demonstrates, for the first time, the growth-promoting effect of the O. picturae strain on soybean seedlings under non-stress conditions. It also highlights its role in enhancing root growth and reducing Cd accumulation in the roots under Cd stress. Additionally, through the utilization of untargeted metabolomics, metagenomics, and transcriptomics for a multi-omics analysis, we investigated the impact of O. picturae on the soil microbiome and its correlation with differential gene expression in plants. This innovative approach unveils the molecular mechanisms underlying O. picturae's promotion of root growth and adaptation to Cd stress.

A fully biodegradable spherical nucleic acid nanoplatform for self-codelivery of doxorubicin and miR122 for innate and adaptive immunity activation.

Facile construction of a fully biodegradable spherical nucleic acid (SNA) nanoplatform is highly desirable for clinical translations but remains rarely explored. We developed herein the first polycarbonate-based biodegradable SNA nanoplatform for self-codelivery of a chemotherapeutic drug, doxorubicin (DOX), and a human liver-specific miR122 for synergistic chemo-gene therapy of hepatocellular carcinoma (HCC). Ring-opening polymerization (ROP) of a carbonate monomer leads to a well-defined polycarbonate backbone for subsequent DOX conjugation to the pendant side chains via acidic pH-cleavage Schiff base links and miR122 incorporation to the chain termini via click coupling, affording an amphiphilic polycarbonate-DOX-miR122 conjugate, PBis-Mpa30-DOX-miR122 that can self-assemble into stabilized SNA. Besides the desired biodegradability, another notable merit of this nanoplatform is the use of miR122 not only for gene therapy but also for enhanced innate immune response. Together with the ICD-triggering effect of DOX, PBis-Mpa30-DOX-miR122 SNA-mediated DOX and miR122 codelivery leads to synergistic immunogenicity enhancement, resulting in tumor growth inhibition value (TGI) of 98.1 % significantly higher than those of the groups treated with only drug or gene in a Hepa1-6-tumor-bearing mice model. Overall, this study develops a useful strategy toward biodegradable SNA construction, and presents a drug and gene-based self-codelivery SNA with synergistic immunogenicity enhancement for efficient HCC therapy. STATEMENT OF SIGNIFICANCE: Facile construction of a fully biodegradable SNA nanoplatform is useful for in vivo applications but remains relatively unexplored likely due to the synthetic challenge. We report herein construction of a polycarbonate-based SNA nanoplatform for co-delivering a chemotherapeutic drug, DOX, and a human liver-specific miR-122 for synergistic HCC treatment. In addition to the desired biodegradability properties, this SNA nanoplatform integrates DOX-triggered ICD and miR-122-enhanced innate immunity for simultaneously activating adaptive and innate immunities, which leads to potent antitumor efficiency with a TGI value of 98.1 % in a Hepa1-6-tumor-bearing mice model.

Otitis media with effusion in adults during the SARS-CoV-2 epidemic.

OBJECTIVES: The purpose of this study was to investigate the fluctuations in the prevalence of individuals diagnosed with otitis media with effusion (OME) during the SARS-CoV-2 pandemic, while also evaluating the persistence of SARS-CoV-2 in middle ear effusion (MEE) and assessing the effectiveness of tympanocentesis as a treatment modality for OME in this specific period. METHODS: The total number of outpatients and patients diagnosed with OME in our department was recorded for January 2022 and January 2023. Thirty patients (aged 15-86 years) were categorized into two groups: group A (n = 12), who developed OME during their SARS-CoV-2 infection and group B (n = 18), who experienced OME after the resolution of SARS-CoV-2 infection. All patients underwent otoendoscopic tympanocentesis (without a ventilation tube), where MEE and nasopharyngeal secretions were simultaneously collected for SARS-CoV-2 detection by polymerase chain reaction. The time interval from SARS-CoV-2 infection to tympanocentesis, results of SARS-CoV-2 detection, preoperative and postoperative average hearing threshold, and Eustachian Tube Dysfunction Questionnaire (ETDQ-7) scores were documented. RESULTS: The proportion of outpatients with OME in January 2023 was higher than that in January 2022. There were five patients who had positive test results for SARS-CoV-2 on MEE after tympanocentesis. These 5 patients underwent tympanocentesis at a mean of 28 ± 7.28 days following confirmation of SARS-CoV-2 infection. The ETDQ-7 scores of group A exhibited a reduction from 21.85 ± 4.8 to 10.00 ± 4.07 following tympanocentesis, while the ETDQ-7 scores of group B also demonstrated a decrease from 21.22 ± 4.65 to 10.11 ± 3.68 after undergoing tympanocentesis. The tympanocentesis was effective in both groups. CONCLUSIONS: The study confirmed that the proportion of outpatients with OME in the Clinics of Otolaryngology during the SARS-CoV-2 epidemic increased significantly. SARS-CoV-2 RNA was detectable in MEE of COVID-19-related OME patients. Tympanocentesis was therapeutic for OME during SARS-CoV-2 infection, which facilitated viral clearance in MEE.

Rolling theory-guided prediction of hot-rolled plate width based on parameter transfer strategy.

Machine learning performs well in many problems. However, the tendency to generate predictions that violate theoretical knowledge makes it difficult to apply to practical processing. To resolve this situation, this paper combines domain knowledge with a data-driven model, proposes a theory-guided machine learning framework based on a parameter transfer strategy, and applies it to the width prediction of plates after multiple passes of hot rolling. The framework applies a swarm optimization algorithm to the original theoretical model and generates numerous highly-physical consistent samples. The established deep neural network (DNN) model is trained with simulated data, and the parameters are fine-tuned using a parameter transfer strategy combined with actual data to ensure excellent adaptation to the actual environment based on adequate learning of theoretical knowledge. In tests, the proposed model had the best overall prediction performance in this paper. Meanwhile, the developed model is consistent with the existing perception of rolling theory. This allows for the quick and reliable application of machine learning models in production.

Ratiometric fluorescent and electrochemiluminescent dual modal assay for detection of 2,6-pyridinedicarboxylic acid as an anthrax biomarker.

2,6-pyridinedicarboxylic acid (DPA) is an excellent biomarker of Bacillus anthracis (B. anthracis). The sensitive detection of DPA, especially through visual point-of-care testing, was significant for accurate and rapid diagnosis of anthrax to timely prevent anthrax disease or biological terrorist attack. Herein, a ratiometric fluorescent (R-FL) and electrochemiluminescent (ECL) dual-mode detection platform with a lanthanide ion-based metal-organic framework (Ln-MOF, i.e., M/Y-X: M = Eu, Y = Tb, and X = 4,4',4″-s-triazine-1,3,5-triyltri-m-aminobenzoic acid) was developed. Eu/Tb-TATAB nanoparticles were constructed to identify DPA. The R-FL detection platform quantitatively detected DPA by monitoring the I545/I617 ratio of the characteristic fluorescence peak intensities of Tb3+ ions and Eu3+ ions. The ECL sensing platform successfully quantified DPA by exploiting the burst effect of DPA on the ECL signal. The above methods had highly sensitive and rapid detection of DPA in water and serum samples. The results showed that this dual-mode detection platform may be projected to be a powerful instrument for preventing related biological warfare and bio-terrorism.

Facile electrochemiluminescence sensing platform based on Gd2O3:Eu3+ nanocrystals for organophosphorus pesticides detection in vegetable samples.

In this work, europium ion-doped gadolinium trioxide nanocrystals (Gd2O3:Eu3+ NCs) were successfully synthesized and applied to construct an electrochemiluminescence (ECL) sensor. Compared with pure Gd2O3, the doping of Eu3+ ions caused enhanced ECL intensity and more stable signals. Based on the excellent ECL performance of Gd2O3:Eu3+ NCs, we constructed a new ECL sensing platform for the detection of organophosphorus pesticides (OPs). The ECL sensor showed a good linear relationship in the concentration range of 1 nM to 1 pM, with a limit of detection of 0.12 pM (S/N = 3) for dichlorvos (DDVP). In addition, the constructed ECL sensor was applied for the detection of DDVP in vegetable samples, and good recoveries were obtained. The results indicated that the ECL sensor exhibited fantastic performance properties and had good application prospects in OPs detection.

COVID-19-related secretory otitis media in the omicron era: a case series.

OBJECTIVES: Increased numbers of patients with secretory otitis media appeared in outpatient clinics after the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron pandemic; however, the relationship between SARS-CoV-2 Omicron variant infection and secretory otitis media is uncertain. METHODS: We performed tympanocentesis and used reverse transcription-polymerase chain reaction (RT-PCR) testing to examine middle ear effusion (MEE) and nasopharyngeal secretions from 30 patients with secretory otitis media associated with SARS-CoV-2 infection. RT-PCR was performed using the open reading frame 1ab and nucleocapsid protein gene kit from Shanghai Berger Medical Technology Co., Ltd., as the sole assay method, in accordance with the manufacturer's instructions. RESULTS: MEEs from 5 of the 30 patients tested positive for SARS-CoV-2, including one patient with positive results for both the nasopharyngeal secretion and MEE. We report and discuss the medical records of six patients, including these five MEE-positive patients and a MEE-negative patient. CONCLUSION: SARS-CoV-2 RNA can be detected in MEE caused by coronavirus disease 2019-related secretory otitis media even when a patient's nasopharyngeal secretion tests PCR-negative for SARS-CoV-2. The virus can remain in the MEE for a long time after SARS-CoV-2 infection.

A Comparative Study of Nanobio Interaction of Zn-Doped CdTe Quantum Dots with Lactoferrin Using Different Spectroscopic Methods.

In this paper, glutathione (GSH)-coated Zn-doped CdTe quantum dots (QDs) with different particle sizes were synthesized using the "reflow method", and the interaction mechanism between the two QDs and lactoferrin (LF) was investigated systemically with different spectroscopic methods. The steady-state fluorescence spectra showed that the LF formed a tight complex with the two QDs through static bursting and that the electrostatic force was the main driving force between the two LF-QDs systems. The complex generation process was found to be spontaneous (ΔG < 0) and accompanied by exothermic and increasing degrees of freedom (ΔH < 0, ΔS > 0) by using the temperature-dependent fluorescence spectroscopy. The critical transfer distance (R0) and donor-acceptor distance (r) of the two LF-QDs systems were obtained based on the fluorescence resonance energy transfer theory. In addition, it was observed that the QDs changed the secondary and tertiary structures of LF, leading to an increase in the hydrophobicity of LF. Further, the nano-effect of orange QDs on LF is much larger than that of green QDs. The above results provide a basis for metal-doped QDs with LF in safe nano-bio applications.

Preparation of a Red-Emitting, Chitosan-Stabilized Copper Nanocluster Composite and Its Application as a Hydrogen Peroxide Detection Probe in the Analysis of Water Samples.

Hydrogen peroxide (H2O2) is an important reactive oxygen species that mediates a variety of physiological functions in biological processes, and it is an essential mediator in food, pharmaceutical, and environmental analysis. However, H2O2 can be dangerous and toxic at certain concentrations. It is crucial to detect the concentration of H2O2 in the environment for human health and environmental protection. Herein, we prepared the red-emitting copper nanoclusters (Cu NCs) by a one-step method, with lipoic acid (LA) and sodium borohydride as protective ligands and reducing agents, respectively, moreover, adding chitosan (CS) to wrap LA-Cu NCs. The as-prepared LA-Cu NCs@CS have stronger fluorescence than LA-Cu NCs. We found that the presence of H2O2 causes the fluorescence of LA-Cu NCs@CS to be strongly quenched. Based on this, a fluorescent probe based on LA-Cu NCs@CS was constructed for the detection of H2O2 with a limit of detection of 47 nM. The results from this research not only illustrate that the as--developed fluorescent probe exhibits good selectivity and high sensitivity to H2O2 in environmental water samples but also propose a novel strategy to prepare red-emitting copper nanoclusters (Cu NCs) by a one-step method.

Electrochemiluminescence Sensor Based on CeO2 Nanocrystalline for Hg2+ Detection in Environmental Samples.

The excessive concentration of heavy-metal mercury ions (Hg2+) in the environment seriously affects the ecological environment and even threatens human health. Therefore, it is necessary to develop rapid and low-cost determination methods to achieve trace detection of Hg2+. In this paper, an Electrochemiluminescence (ECL) sensing platform using a functionalized rare-earth material (cerium oxide, CeO2) as the luminescent unit and an aptamer as a capture unit was designed and constructed. Using the specific asymmetric matching between Hg2+ and thymine (T) base pairs in the deoxyribonucleic acid (DNA) single strand, the "T-Hg-T" structure was formed to change the ECL signal, leading to a direct and sensitive response to Hg2+. The results show a good linear relationship between the concentration and the response signal within the range of 10 pM-100 µM for Hg2+, with a detection limit as low as 0.35 pM. In addition, the ECL probe exhibits a stable ECL performance and excellent specificity for identifying target Hg2+. It was then successfully used for spiked recovery tests of actual samples in the environment. The analytical method solves the problem of poor Hg2+ recognition specificity, provides a new idea for the efficient and low-cost detection of heavy-metal pollutant Hg2+ in the environment, and broadens the prospects for the development and application of rare-earth materials.

Electrochemiluminescence Aptasensor Based on Gd(OH)3 Nanocrystalline for Ochratoxin A Detection in Food Samples.

In the present study, the electrochemiluminescence (ECL) properties of Gd(OH)3 nanocrystals with K2S2O8 as the cathode coreactant were studied for the first time. Based on the prominent ECL behavior of this material and the excellent specificity of the aptamer technique, an ECL aptasensor for the detection of ochratoxin A (OTA) was formulated successfully. Over an OTA concentration range of 0.01 pg mL-1 to 10 ng mL-1, the change in the ECL signal was highly linear with the OTA concentration, and the limit of detection (LOD) was 0.0027 pg mL-1. Finally, the ECL aptasensor was further used to detect OTA in real samples (grapes and corn) and satisfactory results were obtained, which indicated that the built method is expected to be applied in food detection.

Sensitive and Facile HCOOH Fluorescence Sensor Based on Highly Active Ir Complexes' Catalytic Transfer Hydrogen Reaction.

With several major polarity and weak optical properties, the sensitive detection of HCOOH remains a major challenge. Given the special role of HCOOH in assisting in the catalytic hydrogenation process of Ir complexes, HCOOH (as a hydrogen source) could rapidly activate Ir complexes as catalysts and further reduce the substrates. This work developed a facile and sensitive HCOOH fluorescence sensor utilizing an optimal catalytic fluorescence generation system, which consists of the phenyl-pyrazole-type Ir-complex PP-Ir-Cl and the coumarin-type fluorescence probe P-coumarin. The sensor demonstrates excellent sensitivity and specificity for HCOOH and formates; the limits of detection for HCOOH, HCOONa, and HCOOEt3N were tested to be 50.6 ppb, 68.0 ppb, and 146.0 ppb, respectively. Compared to previous methods, the proposed sensor exhibits good detection accuracy and excellent sensitivity. Therefore, the proposed HCOOH sensor could be used as a new detection method for HCOOH and could provide a new design path for other sensors.

Toxicity Assessment of the Binary Mixtures of Aquatic Organisms Based on Different Hypothetical Descriptors.

Modern industrialization has led to the creation of a wide range of organic chemicals, especially in the form of multicomponent mixtures, thus making the evaluation of environmental pollution more difficult by normal methods. In this paper, we attempt to use forward stepwise multiple linear regression (MLR) and nonlinear radial basis function neural networks (RBFNN) to establish quantitative structure-activity relationship models (QSARs) to predict the toxicity of 79 binary mixtures of aquatic organisms using different hypothetical descriptors. To search for the proper mixture descriptors, 11 mixture rules were performed and tested based on preliminary modeling results. The statistical parameters of the best derived MLR model were Ntrain = 62, R2 = 0.727, RMS = 0.494, F = 159.537, Q2LOO = 0.727, and Q2pred = 0.725 for the training set; and Ntest = 17, R2 = 0.721, RMS = 0.508, F = 38.773, and q2ext = 0.720 for the external test set. The RBFNN model gave the following statistical results: Ntrain = 62, R2 = 0.956, RMS = 0.199, F = 1279.919, Q2LOO = 0.955, and Q2pred = 0.855 for the training set; and Ntest = 17, R2 = 0.880, RMS = 0.367, F = 110.980, and q2ext = 0.853 for the external test set. The quality of the models was assessed by validating the relevant parameters, and the final results showed that the developed models are predictive and can be used for the toxicity prediction of binary mixtures within their applicability domain.

Generation of an induced pluripotent stem cell lines HMSCASTi002-A from peripheral blood mononuclear cells of a 38-year-old healthy female individual.

Peripheral blood mononuclear cells (PBMCs) of a 38-year-old healthy female were isolated and reprogrammed into the induced pluripotent stem cells (iPSCs). The established iPSC line expressed various pluripotency stem cell markers and potential of differentiating into three germ layers, meanwhile maintained normal karyotype.

Generation of an induced pluripotent stem cell lines HMSCASTi001-A from peripheral blood mononuclear cells of a 35-year-old healthy male.

Peripheral blood mononuclear cells derived from a 35-year-old healthy male were reprogrammed into induced pluripotent stem cells (iPSCs). The iPSCs maintained a normal karyotype, expressed various pluripotency stem cell markers, and showed potential of differentiating into three germ layers. This iPSCs could be differentiated into multiple cell subtypes for drug discovery and investigation of mechanisms.

Identification of molecular initiating events and key events leading to endocrine disrupting effects of PFOA: Integrated molecular dynamic, transcriptomic, and proteomic analyses.

Perfluorooctanoic acid (PFOA) can rapidly activate signaling pathways independent of nuclear hormone receptors through membrane receptor regulation, which leads to endocrine disrupting effects. In the present work, the molecular initiating event (MIE) and the key events (KEs) which cause the endocrine disrupting effects of PFOA have been explored and determined based on molecular dynamics simulation (MD), fluorescence analysis, transcriptomics, and proteomics. MD modeling and fluorescence analysis proved that, on binding to the G protein-coupled estrogen receptor-1 (GPER), PFOA could induce a conformational change in the receptor, turning it into an active state. The results also indicated that the binding to GPER was the MIE that led to the adverse outcome (AO) of PFOA. In addition, the downstream signal transduction pathways of GPER, as regulated by PFOA, were further investigated through genomics and proteomics to identify the KEs leading to thr endocrine disrupting effects. Two pathways (Endocrine resistance, ERP and Estrogen signaling pathway, ESP) containing GPER were regulated by different concentration of PFOA and identified as the KEs. The knowledge of MIE, KEs, and AO of PFOA is necessary to understand the links between PFOA and the possible pathways that lead to its negative effects.

A Novel Turn-On Fluorescent Sensor Based on Sulfur Quantum Dots and MnO2 Nanosheet Architectures for Detection of Hydrazine.

In this paper, the SQDs@MnO2 NS as the probe was applied to construct a novel "turn-on" fluorescent sensor for sensitive and selective detection of hydrazine (N2H4). Sulfur quantum dots (SQDs) and MnO2 nanosheets (MnO2 NS) were simply mixed, through the process of adsorption to prepare the architectures of SQDs@MnO2 NS. The fluorescent emissions of SQDs@MnO2 NS play a key role to indicate the state of the sensor. According to the inner filter effect (IFE) mechanism, the state of the sensor at the "off" position, or low emission, under the presence of MnO2 NS, is which the ultraviolet and visible spectrum overlaps with the fluorescence emission spectrum of SQDs. Under the optimal conditions, the emission was gradually recovered with the addition of the N2H4, since the N2H4 as a strong reductant could make the MnO2 NS converted into Mn2+, the state of the sensor at the "on". Meanwhile, the fluorescent sensor possesses good selectivity and high sensitivity, and the detection concentration of N2H4 with a wide range from 0.1 µM to 10 mM with a detection limit of 0.072 µM. Furthermore, actual samples were successful in detecting certain implications, indicating that the fluorescent sensor possesses the potential application ability to monitor the N2H4 in the water.

Self-luminescent europium based metal organic frameworks nanorods as a novel electrochemiluminescence chromophore for sensitive ulinastatin detection in biological samples.

In this work, we developed a novel electrochemiluminescence (ECL) biosensor for ulinastatin (UTI) detection based on self-luminescent metal-organic framework (L-MOF) nanomaterials. The L-MOFs could be simply prepared by one-pot methods using Eu3+ and 4,4',4″-s-triazine-1,3,5-triyltri-m-aminobenzoic acid (H3TATAB) as the metallic center and organic ligand, respectively. The Eu-TATAB exhibited high efficiency and stable ECL performance when using K2S2O8 as coreactant. For the established biosensor, Eu-TATAB was both used as the ECL chromophore and protein carrier due to its outstanding biocompatibility and large superficial area, which could load sufficient antibodies to link with antigen in the biosensor for subsequent detection. The established sandwich ECL biosensor showed a wide linear range of 0.1 ng mL-1 - 105 ng mL-1 and a low limit of detection of 9.7 pg mL-1 for UTI detection. In addition, the developed ECL biosensor could also be successfully applied to the real UTI sample determination in serum. The reported biosensor strategy could provide a guide for developing more other novel and promising high-performance ECL nanomaterials, and also be used as a potential method for ultrasensitive UTI detection in disease research.