Search Results (6,183)

Cellular immunity is critical for the regulation of viral diseases, including coronavirus disease 2019 (COVID-19), and is generally considered immature in childhood. However, the details of cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among children are unclear. We assessed cellular immunity in eight children post-vaccination against SARS-CoV-2 and 11 children after SARS-CoV-2 infection using the T-SPOT^®.COVID assay for the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT^®.COVID assay for the S protein yielded positive results in seven children. In the post-infection group, the assay for the N protein was positive for 5 of 11 children, with 3 of these 5 children requiring hospitalization, including 2 who needed mechanical ventilation. The T-SPOT^®.COVID assay is thus valuable for assessing cellular immunity against SARS-CoV-2, and most children infected with SARS-CoV-2 may not develop such immunity unless the disease severity is significant. Full article

With the development of rice varieties and mechanized planting technology, reliable and efficient nitrogen and planting density status diagnosis and recommendation methods have become critical to the success of precise nitrogen and planting density management in crops. In this study, we combined population structure, plant shape characteristics, environmental weather conditions, and management information data using a machine learning model to simulate the responses of the yield and nitrogen nutrition index and developed an ensemble learning model-based nitrogen and planting density recommendation strategy for different varieties of rice types. In the third stage, the NNI and yield prediction effect of the ensemble learning model was more significantly improved than that of the other two stages. The scenario analysis results show that the optimal yields and nitrogen nutrition indices were obtained with a density and nitrogen amount of 100.1 × 10⁴ plant/ha and 161.05 kg·ha⁻¹ for the large-spike type variety of rice, 75.08 × 10⁴ plant/ha and 159.52 kg·ha⁻¹ for the intermediate type variety of rice, and 75.08 × 10⁴ plant/ha and 133.47 kg·ha⁻¹ for the panicle number type variety of rice, respectively. These results provide a scientific basis for the nitrogen application and planting density for a high yield and nitrogen nutrition index of rice in northeast China. Full article

Aflatoxins (AFs) including AFB₁, AFB₂, AFG₁ and AFG₂ are widely found in agriculture products, and AFB₁ is considered one of the most toxic and harmful mycotoxins. Herein, a highly sensitive (at the pg mL⁻¹ level) and group-specific enzyme-linked immunosorbent assay (ELISA) for the detection of AFB₁ in agricultural and aquiculture products was developed. The AFB₁ derivative containing a carboxylic group was synthesized and covalently linked to bovine serum albumin (BSA). The AFB₁-BSA conjugate was used as an immunogen to immunize mice. A high-quality monoclonal antibody (mAb) against AFB₁ was produced by hybridoma technology, and the mAb-based ELISA for AFB₁ was established. IC₅₀ and limit of detection (LOD) of the ELISA for AFB₁ were 90 pg mL⁻¹ and 18 pg mL⁻¹, respectively. The cross-reactivities (CRs) of the assay with AFB₂, AFG₁, and AFG₂ were 23.6%, 42.5%, and 1.9%, respectively, revealing some degree of group specificity. Corn flour, wheat flour, and crab roe samples spiked with different contents of AFB₁ were subjected to ELISA procedures. The recoveries and relative standard deviation (RSD) of the ELISA for AFB₁ in spiked samples were 78.3–116.6% and 1.49–13.21% (n = 3), respectively. Wheat flour samples spiked with the mixed AF (AFB₁, AFB₂, AFG₁, AFG₂) standard solution were measured by ELISA and LC-MS/MS simultaneously. It was demonstrated that the proposed ELISA can be used as a screening method for evaluation of AFs (AFB₁, AFB₂, AFG₁, AFG₂) in wheat flour samples. Full article

Mass spectrometry (MS)-based clinical metabolomics is very promising for the discovery of new biomarkers and diagnostics. However, poor data accuracy and reproducibility limit its true potential, especially when performing data analysis across multiple sample sets. While high-resolution mass spectrometry has gained considerable popularity for discovery metabolomics, triple quadrupole (QqQ) instruments offer several benefits for the measurement of known metabolites in clinical samples. These benefits include high sensitivity and a wide dynamic range. Here, we present the Olaris Global Panel (OGP), a HILIC LC-QqQ MS method for the comprehensive analysis of ~250 metabolites from all major metabolic pathways in clinical samples. For the development of this method, multiple HILIC columns and mobile phase conditions were compared, the robustness of the leading LC method assessed, and MS acquisition settings optimized for optimal data quality. Next, the effect of U-¹³C metabolite yeast extract spike-ins was assessed based on data accuracy and precision. The use of these U-¹³C-metabolites as internal standards improved the goodness of fit to a linear calibration curve from r² < 0.75 for raw data to >0.90 for most metabolites across the entire clinical concentration range of urine samples. Median within-batch CVs for all metabolite ratios to internal standards were consistently lower than 7% and less than 10% across batches that were acquired over a six-month period. Finally, the robustness of the OGP method, and its ability to identify biomarkers, was confirmed using a large sample set. Full article

Magnetic resonance sounding is a geophysical method for quantitatively determining the state for groundwater storage that has gained international attention in recent years. However, the practical acquisition of magnetic resonance sounding signals, which are on the nanovolt scale, is susceptible to various types of interference, such as power-line harmonics, random noise, and spike noise. Such interference can degrade the quality of magnetic resonance sounding signals and, in severe cases, be completely drowned out by noise. This paper introduces an adaptive Gaussian filtering algorithm that is well-suited for handling intricate noise signals due to its adaptive solving characteristics and iterative sifting approach. Notably, the algorithm can process signals without relying on prior knowledge. The adaptive Gaussian filtering algorithm is applied for the envelope extraction of noisy magnetic resonance sounding signals, and the reliability and effectiveness of the method are rigorously validated. The simulation results reveal that, even under strong noise interference (with original signal-to-noise ratios ranging from −7 dB to −25 dB), the magnetic resonance sounding signal obtained after algorithmic processing is compared to the ideal signal, with 16 sets of data statistics, and the algorithm ensures an initial amplitude uncertainty within 4nV and restricts the uncertainty of the relaxation time within a 6 ms range. The signal-to-noise ratio can be boosted by up to 53 dB. The comparative assessments with classical algorithms such as empirical mode decomposition and the harmonic modeling method confirm the superior performance of the adaptive Gaussian filtering algorithm. The processing of the field data also fully proved the practical application effects of the algorithm. Full article

SARS-CoV-2 vaccines have contributed to attenuating the burden of the COVID-19 pandemic by promoting the development of effective immune responses, thus reducing the spread and severity of the pandemic. A clinical trial with the Sputnik-V vaccine was conducted in Venezuela from December 2020 to July 2021. The aim of this study was to explore the antibody reactivity of vaccinated individuals towards different regions of the spike protein (S). Neutralizing antibody (NAb) activity was assessed using a commercial surrogate assay, detecting NAbs against the receptor-binding domain (RBD), and a plaque reduction neutralization test. NAb levels were correlated with the reactivity of the antibodies to the spike regions over time. The presence of Abs against nucleoprotein was also determined to rule out the effect of exposure to the virus during the clinical trial in the serological response. A high serological reactivity was observed to S and specifically to S1 and the RBD. S2, although recognized with lower intensity by vaccinated individuals, was the subunit exhibiting the highest cross-reactivity in prepandemic sera. This study is in agreement with the high efficacy reported for the Sputnik V vaccine and shows that this vaccine is able to induce an immunity lasting for at least 180 days. The dissection of the Ab reactivity to different regions of S allowed us to identify the relevance of epitopes outside the RBD that are able to induce NAbs. This research may contribute to the understanding of vaccine immunity against SARS-CoV-2, which could contribute to the design of future vaccine strategies. Full article

Harmful substances in consumer goods pose serious hazards to human health and the environment. However, due to the vast variety of consumer goods and the complexity of their substrates, it is difficult to simultaneously detect multiple harmful substances in different materials. This paper presents a method for the simultaneous determination of 41 harmful substances comprising 17 phthalates (PAEs), 8 organophosphate flame retardants (OPFRs), and 16 polycyclic aromatic hydrocarbons (PAHs) in five types of products using the matrix-matching calibration strategy. The method employs an efficient ultrasonic extraction procedure using a mixture of dichloromethane and methylbenzene, followed by dissolution–precipitation and analysis through gas chromatography–mass spectrometry. Compared with previous experiments, we established a universal pretreatment method suitable for multi-matrix materials to simultaneously determine multiple harmful substances. To evaluate the effects of the matrix on the experimental results, we compared neat standard solutions and matrix-matching standard solutions. The results demonstrated that all compounds were successfully separated within 30 min with excellent separation efficiency. Additionally, the linear relationships of all analytes showed strong correlation coefficients (R²) of at least 0.995, ranging from 0.02 mg/L to 20 mg/L. The average recoveries of the target compounds (spiked at three concentration levels) were between 73.6 and 124.1%, with a relative standard deviation (n = 6) varying from 1.2% to 9.9%. Finally, we tested 40 different materials from consumer products and detected 16 harmful substances in 31 samples. Overall, this method is simple and accurate, and it can be used to simultaneously determine multiple types of hazardous substances in multi-matrix materials by minimizing matrix effects, making it an invaluable tool for ensuring product safety and protecting public health. Full article

The src homology 2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are two proteins involved in intracellular signaling pathways and have been linked to the pathogenesis of several diseases. Both protein paralogs are well known for their involvement in the formation of various kinds of cancer. SHIP1, which is expressed predominantly in hematopoietic cells, has been implicated as a tumor suppressor in leukemogenesis especially in myeloid leukemia, whereas SHIP2, which is expressed ubiquitously, has been implicated as an oncogene in a wider variety of cancer types and is suggested to be involved in the process of metastasis of carcinoma cells. However, there are numerous other diseases, such as inflammatory diseases as well as allergic responses, Alzheimer’s disease, and stroke, in which SHIP1 can play a role. Moreover, SHIP2 overexpression was shown to correlate with opsismodysplasia and Alzheimer’s disease, as well as metabolic diseases. The SHIP1-inhibitor 3-α-aminocholestane (3AC), and SHIP1-activators, such as AQX-435 and AQX-1125, and SHIP2-inhibitors, such as K161 and AS1949490, have been developed and partly tested in clinical trials, which indicates the importance of the SHIP-paralogs as possible targets in the therapy of those diseases. The aim of this article is to provide an overview of the current knowledge about the involvement of SHIP proteins in the pathogenesis of cancer and other human diseases and to create awareness that SHIP1 and SHIP2 are more than just tumor suppressors and oncogenes. Full article

As a necessary sulfhydryl amino acid, L-cysteine (L-Cys) maintains many physiological functions in the biological system. However, abnormal L-Cys levels can cause a variety of diseases. In our work, a highly sensitive and selective assay has been developed for sensing L-Cys using the morphological transformation of silver-based materials induced by Cr³⁺. In this sensing system, Cr³⁺ could etch the silver nanoflakes into silver nanoparticles, accompanied by a change in absorbance, which decreases at 395 nm, creates a new peak at 538 nm, and keeps increasing the absorbance with the addition of Cr³⁺ concentration. Meanwhile, under the naked eye, the solution color changes from bright yellow to dark purple. Because of the strong affinity between L-Cys and Cr³⁺, L-Cys could inhibit the induction of Cr³⁺ on silver-based materials, thereby preventing changes in the configuration, absorption spectrum, and color of silver-based materials. Taking advantage of this point, we can quantitatively detect the concentration of L-Cys. A linear relationship between the absorbance ratio (A538 nm/A395 nm) and L-Cys concentration was found in the range of 0.1–0.9 μM, and the detection limit was 41.2 nM. The strategy was applied to measure L-Cys spiked in beer and urine samples, with recovery from 93.80 to 104.03% and 93.33% to 107.14% and RSD from 0.89 to 2.40% and 1.80% to 6.78%, respectively. This detection strategy demonstrates excellent selectivity and sensitivity, which makes it a practical and effective method for the detection of L-Cys in real samples. Full article

Neutralizing antibodies targeting the spike (S) protein of SARS-CoV-2, elicited either by natural infection or vaccination, are crucial for protection against the virus. Nonetheless, the emergence of viral escape mutants presents ongoing challenges by contributing to breakthrough infections. To define the evolution trajectory of SARS-CoV-2 within the immune population, we co-incubated replication-competent rVSV/SARS-CoV-2/GFP chimeric viruses with sera from COVID-19 convalescents. Our findings revealed that the E484D mutation contributes to increased viral resistant against both convalescent and vaccinated sera, while the L1265R/H1271Y double mutation enhanced viral infectivity in 293T-hACE2 and Vero cells. These findings suggest that under the selective pressure of polyclonal antibodies, SARS-CoV-2 has the potential to accumulate mutations that facilitate either immune evasion or greater infectivity, facilitating its adaption to neutralizing antibody responses. Although the mutations identified in this study currently exhibit low prevalence in the circulating SARS-CoV-2 populations, the continuous and meticulous surveillance of viral mutations remains crucial. Moreover, there is an urgent necessity to develop next-generation antibody therapeutics and vaccines that target diverse, less mutation-prone antigenic sites to ensure more comprehensive and durable immune protection against SARS-CoV-2. Full article

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise the effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, the mechanism of infection, the role of angiotensin-converting enzyme 2, the host defence responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants. Full article

The presence of plastic particles in oceans has been recognized as a major environmental concern. The decrease in particle size increases their ability to directly interact with biota, with particles in the nanometer size range (nanoplastics—NPs) displaying a higher ability to penetrate biological membranes, which increases with the decrease in particle size. This study aimed to evaluate the role of life stages in the effects of poly(methyl)methacrylate (PMMA) NPs on the polychaete Hediste diversicolor, a key species in the marine food web and nutrient cycle. Thus, behavioral (burrowing activity in clean and spiked sediment) and biochemical endpoints (neurotransmission, energy reserves, antioxidant defenses, and oxidative damage) were assessed in juvenile and adult organisms after 10 days of exposure to spiked sediment (between 0.5 and 128 mg PMMA NPs/Kg sediment). Overall, the results show that H. diversicolor is sensitive to the presence of PMMA NPs. In juveniles, exposed organisms took longer to burrow in sediment, with significant differences from the controls being observed at all tested concentrations when the test was performed with clean sediment, whereas in PMMA NP-spiked sediment, effects were only found at the concentrations 8, 32, and 128 mg PMMA NPs/Kg sediment. Adults displayed lower sensitivity, with differences to controls being found, for both sediment types, at 8, 32, and 128 mg PMMA NPs/Kg sediment. In terms of Acetylcholinesterase, used as a marker of effects on neurotransmission, juveniles and adults displayed opposite trends, with exposed juveniles displaying increased activity (suggesting apoptosis), whereas in adults, overall decreased activity was found. Energy-related parameters revealed a generally similar pattern (increase in exposed organisms) and higher sensitivity in juveniles (significant effects even at the lower concentrations). NPs also demonstrated the ability to increase antioxidant defenses (higher in juveniles), with oxidative damage only being found in terms of protein carbonylation (all tested NPs conditions) in juveniles. Overall, the data reveal the potential of PMMA NPs to affect behavior and induce toxic effects in H. diversicolor, with greater effects in juveniles. Full article

Since the outbreak of COVID-19, researchers have been working tirelessly to discover effective ways to combat coronavirus infection. The use of computational drug repurposing methods and molecular docking has been instrumental in identifying compounds that have the potential to disrupt the binding between the spike glycoprotein of SARS-CoV-2 and human ACE2 (hACE2). Moreover, the pseudovirus approach has emerged as a robust technique for investigating the mechanism of virus attachment to cellular receptors and for screening targeted small molecule drugs. Pseudoviruses are viral particles containing envelope proteins, which mediate the virus’s entry with the same efficiency as that of live viruses but lacking pathogenic genes. Therefore, they represent a safe alternative to screen potential drugs inhibiting viral entry, especially for highly pathogenic enveloped viruses. In this review, we have compiled a list of antiviral plant extracts and natural products that have been extensively studied against enveloped emerging and re-emerging viruses by pseudovirus technology. The review is organized into three parts: (1) construction of pseudoviruses based on different packaging systems and applications; (2) knowledge of emerging and re-emerging viruses; (3) natural products active against pseudovirus-mediated entry. One of the most crucial stages in the life cycle of a virus is its penetration into host cells. Therefore, the discovery of viral entry inhibitors represents a promising therapeutic option in fighting against emerging viruses. Full article

Patients with multiple myeloma (MM) are a heterogenous, immunocompromised group with increased risk for COVID-19 morbidity and mortality but impaired responses to primary mRNA SARS-CoV-2 vaccination. The effects of booster vaccinations and breakthrough infections (BTIs) on antibody (Ab) levels and cross-protection to variants of concern (VOCs) are, however, not sufficiently evaluated. Therefore, we analysed humoral and cellular vaccine responses in MM patients stratified according to disease stage/treatment into group (1) monoclonal gammopathy of undetermined significance, (2) after stem cell transplant (SCT) without immunotherapy (IT), (3) after SCT with IT, and (4) progressed MM, and in healthy subjects (prospective cohort study). In contrast to SARS-CoV-2 hu-1-specific Ab levels, Omicron-specific Abs and their cross-neutralisation capacity remained low even after three booster doses in a majority of MM patients. In particular, progressed MM patients receiving anti-CD38 mAb and those after SCT with IT were Ab low responders and showed delayed formation of spike-specific B memory cells. However, MM patients with hybrid immunity (i.e., vaccination and breakthrough infection) had improved cross-neutralisation capacity against VOCs, yet in the absence of severe COVID-19 disease. Our results indicate that MM patients require frequent variant-adapted booster vaccinations and/or changes to other vaccine formulations/platforms, which might have similar immunological effects as BTIs. Full article

An interleaved high voltage gain DC-DC converter with winding-cross-coupled inductors (WCCIs) and voltage multiplier cells is proposed for photovoltaic systems. The converter configuration is based on the interleaved boost converter integrating the diode-capacitor clamp circuits, the winding-cross-coupled inductors, and voltage multiplier cells to increase the voltage gain and reduce the semiconductor voltage stresses. The equal current sharing of two phases is achieved with the help of the winding-cross-coupled inductors. The converter achieves high voltage gain while operating at a proper duty ratio. The low-voltage-rated MOSFETs with low on-resistance are available to reduce the conduction losses due to the low switch voltage stress. The leakage energy of the coupled inductors is recycled such that the voltage spikes on the power switches are avoided. The input current ripple is decreased due to the interleaved operation. The operating principle and steady-state analysis of the proposed converter are proposed in detail. The design guidelines of the proposed converter are given. In addition, the closed-loop controlled system of the proposed converter is designed to diminish the effect of the variations in input voltage and load on the output voltage. Finally, the experimental results of a 1000 W converter prototype with 36 V input and 400 V output are given to validate the theoretical analysis and the converter performance. Full article