Identification and functional prediction of miRNAs that regulate ROS levels in dielectric barrier discharge plasma-treated boar spermatozoa.

Dielectric barrier discharge (DBD) plasma regulates the levels of reactive oxygen species (ROS), which are critical for sperm quality. MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which regulate post-transcriptional gene expression in animals. At present, it is unknown whether DBD plasma can regulate sperm ROS levels through miRNAs. To further understand the regulatory mechanism of DBD plasma on sperm ROS levels, miRNAs in fresh boar spermatozoa were detected using Illumina deep sequencing technology. We found that 25 known miRNAs and 50 novel miRNAs were significantly upregulated, and 14 known miRNAs and 74 novel miRNAs were significantly downregulated in DBD plasma-treated spermatozoa. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that target genes of differentially expressed miRNAs were involved in many activities and pathways associated with antioxidants. We verified that DBD plasma significantly increased boar sperm quality and reduced ROS levels. These results suggest that DBD plasma can improve sperm quality by regulating ROS levels via miRNAs. Our findings provide a potential strategy to improve sperm quality through miRNA-targeted regulation of ROS, which helps to increase male reproduction and protect cryopreserved semen in clinical practice.

Revealing the effects and mechanism of wine processing on Corni Fructus using chemical characterization integrated with multi-dimensional analyses.

Corni fructus (CF) is always subjected to wine processing before prescription in clinic, for an enhancing effect of nourishing liver and kidney. While, the underlying mechanism for this processing on CF remains obscure. In this study, a sensitive ultra-high-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method combined multi-dimensional analyses was established to monitor chemical characterizations of raw and wine-processed CF (WCF) and hence reveal the effects and underlying mechanism of wine processing on CF. As indicated, a total of 216 compounds were tentatively identified, including 98 structurally complex and variable home/hetero-polymers, that were composed of iridoid glucosides, gallic acids, caffeic acid and/or 5-HMF. Interestingly, 53 of these compounds probably characterized potential novel, including 35 iridoid glucosides or their dimers, 9 iridoid glucoside-gallic acid dimers, 7 gallic acids derivatives and 2 gallic acid-caffeic acid dimers, which provides ideas for natural product researchers. Meanwhile, the multi-dimensional analyses including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and linear regression analysis were used to explore the differences between CF and WCF. The results showed that 23 compounds as chemical markers greatly contributing to the distinction were screened out, and 3 of which (7α/ß-O-ethyl-morroniside, gallic acid and 5-HMF) in WCF indicated an increasing trend in intensities in relative to those in CF. Additionally, linear regression analysis showed that in WCF 53 compounds exhibited an increasing in intensities, while 132 ones did a decreasing trend, compared with those in CF. As our investigation demonstrated, acetal reaction of morroniside, ester hydrolysis in different organic acid derivatives as well as glycoside bond cleavage during wine processing probably resulted in the distinctions. The findings of this study provide a further understanding of the effect and mechanism of wine processing on CF.

SARS-CoV-2 seroprevalence and associated factors among people living with HIV in Sierra Leone.

BACKGROUND: Human immunodeficiency virus (HIV) infection is an important risk factor for Coronavirus Disease 2019 (COVID-19), but data on the prevalence of COVID-19 among people living with HIV (PLWH) is limited in low-income countries. Our aim was to assess the seroprevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies and associated factors among PLWH in Sierra Leone. METHODS: We conducted a cross-sectional survey of PLWH aged 18 years or older in Sierra Leone between August 2022 and January 2023. Participants were tested for SARS-CoV-2 antibodies using a rapid SARS-CoV-2 antibody (immunoglobulin M/immunoglobulin G [IgG]) kits. Stepwise logistic regression was used to explore factors associated with SARS-CoV-2 antibody seroprevalence with a significance level of p < .05. RESULTS: In our study, 33.4% (1031/3085) participants had received a COVID-19 vaccine, and 75.7% were SARS-CoV-2 IgG positive. Higher IgG seroprevalence was observed in females (77.2% vs. 71.4%, p = .001), adults over 60 years (88.2%), those with suppressed HIV RNA (80.7% vs. 51.7%, p < .001), antiretroviral therapy (ART)-experienced individuals (77.9% vs. 44.6%, p < .001), and vaccinated participants (80.7% vs. 73.2%, p < .001). Patients 60 years or older had the highest odds of IgG seroprevalence (adjusted odds ratio [aOR] = 2.73, 95% CI = 1.68-4.65). Female sex (aOR = 1.28, 95%CI = 1.05-1.56), COVID-19 vaccination (aOR = 1.54, 95% CI = 1.27-1.86), and ART (aOR = 2.20, 95% CI = 1.56-3.11) increased the odds, whereas HIV RNA ≥ 1000 copies/mL (aOR = 0.32, 95% CI = 0.26-0.40) reduced the odds of IgG seroprevalence. CONCLUSIONS: We observed a high seroprevalence of SARS-CoV-2 antibody among PLWH in Sierra Leone. We recommend the introduction of targeted vaccination for PLWH with a high risk of severe COVID-19, especially those with an unsuppressed HIV viral load.

Prevalence of congenital cryptorchidism in China: A nationwide population-based surveillance study, 2007-2021.

BACKGROUND: Despite cryptorchidism being a common genital abnormality in male newborns with significant prevalence variations globally, there is a notable scarcity of epidemiological data on this condition in China. OBJECTIVE: This study aimed to delineate the prevalence pattern of cryptorchidism in Chinese population over the past 15 years using nationwide surveillance data. MATERIALS AND METHODS: Data from the China National Population-based Birth Defects Surveillance System (2007-2021) were analyzed to calculate the prevalence rates of cryptorchidism, stratified by birth year, maternal age, maternal residence, and geographic region. Adjusted prevalence rate ratios were computed using Poisson regression, while trends in prevalence and average annual percent change (AAPC) were assessed using the joinpoint regression model. RESULTS: During the study period, a total of 1,833 cases of cryptorchidism were identified among 2,565,964 full-term male births, resulting in prevalence rates of 7.14, 5.60, and 1.54 per 10,000 births for overall, isolated, and associated cryptorchidism, respectively. The overall prevalence increased from 3.86 to 11.20 per 10,000 births, with an AAPC of 7.9% (95% confidence interval: 5.5-11.0). Significant variations were observed across maternal age (< 20 years, 7.62/10,000; 20-24 years, 6.14/10,000; 25-29 years, 6.96/10,000; 30-34 years, 7.48/10,000; ≥35 years, 9.22/10,000), maternal residence (urban vs. rural, 10.99/10,000 vs. 2.86/10,000), and geographic region (eastern, 12.38/10,000; central, 2.36/10,000; western, 2.63/10,000). Approximately one-third of cryptorchidism cases were bilaterally, while two-thirds were unilateral. Commonly observed associated abnormalities included congenital hydrocele testis, as well as anomalies in the genital organs, circulatory system, and musculoskeletal system. CONCLUSION: Despite lower rates compared to other countries, the increasing trend in prevalence of cryptorchidism necessitates further investigation and intervention.

[Chest computed tomography manifestations in neonates with chronic granulomatous disease]. / æ–°ç”Ÿå„¿æ ¢æ€§è‚‰èŠ½è‚¿ç— èƒ¸éƒ¨è®¡ç®—æœºæ–­å±‚æ‰«æçš„ç‰¹å¾åˆ†æž.

OBJECTIVES: To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. METHODS: A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. RESULTS: Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). CONCLUSIONS: The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.

Antibiotic prophylaxis for surgical wound infections in clean and clean-contaminated surgery: an updated systematic review and meta-analysis.

BACKGROUND: The efficacy and necessity of prophylactic antibiotics in clean and clean-contaminated surgery remains controversial. METHODS: The studies were screened and extracted using databases including PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials.gov according to predefined eligibility criteria. Randomized controlled trials (RCTs) comparing the effect of preoperative and postoperative prophylactic antibiotic use on the incidence of surgical site infections (SSIs) in patients undergoing any clean or clean-contaminated surgery. RESULTS: A total of 16,189 participants in 48 RCTs were included in the primary meta-analysis following the eligibility criteria. The pooled odds ratio (OR) for SSI with antibiotic prophylaxis versus placebo was 0.60 (95% CI: 0.53-0.68). The pooled OR among gastrointestinal, oncology, orthopedics, neurosurgery, oral, and urology surgery was 3.06 (95% CI: 1.05-8.91), 1.16 (95% CI: 0.89-1.50), 2.04 (95% CI: 1.09-3.81), 3.05 (95% CI: 1.25-7.47), 3.55 (95% CI: 1.78-7.06), and 2.26 (95% CI: 1.12-4.55), respectively. Furthermore, the summary mean difference (MD) for patients' length of hospitalization was -0.91 (95% CI: -1.61, -0.16). The results of sensitivity analyses for all combined effect sizes showed good stability. CONCLUSION: Antibiotics are both effective, safe, and necessary in preventing surgical wound infections in clean and clean-contaminated procedures, attributed to their reduction in the incidence of surgical site infections as well as the length of patient hospitalization.

Diarylheptanoid glycosides from Dioscorea nipponica rhizomes.

A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A-F (1-6), together with six known diarylheptanoids (7-12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 µM.

Global emergence of double and multi-carbapenemase producing organisms: epidemiology, clinical significance, and evolutionary benefits on antimicrobial resistance and virulence.

Redundant carbapenemase-producing (RCP) bacteria, which carry double or multiple carbapenemases, represent a new and concerning phenomenon. The objective of this study is to conduct a comprehensive analysis of the epidemiology and genetic mechanisms of RCP strains to support targeted surveillance and control measures. A retrospective analysis was conducted using surveillance data from 277 articles. Statistical analysis was performed to determine and evaluate species prevalence, proportions of carbapenemases, antibiotic susceptibility profiles, sample information, and patient outcomes. Complete plasmid sequencing data were utilized to investigate potential antimicrobial resistance or virulence advantages that strains may gain from acquiring redundant carbapenemases. RCP bacteria are widely distributed globally, and their prevalence is increasing over time. Several countries, including China, India, Iran, Turkey, and South Korea, have reported more than 100 RCP strains. The most commonly reported RCP species are Klebsiella pneumoniae and Acinetobacter baumannii, which exhibit varying proportions of carbapenemase combinations. Certain species-carbapenemase combinations, such as K. pneumoniae carrying New Delhi metallo-ß-lactamase (NDM) + oxacillinase (OXA) (56.76%) and K. pneumoniae carbapenemase (KPC) + Verona integron-encoded metallo-ß-lactamase (VIM) (50.00%) carbapenemases, are associated with high mortality rates. In patients with RCP strains isolated from the bloodstream and respiratory system, the mortality rates are 58.70% and 69.23%, respectively. Analysis of plasmids from RCP strains suggests that they may acquire additional antibiotic resistance phenotypes and virulence factors. Carbapenem-resistant bacteria carrying redundant carbapenemases pose a significant global health threat. This study provides valuable insights into the epidemiology and genetic mechanisms of these bacteria, supporting the development of effective control and prevention strategies to mitigate their transmission.IMPORTANCEThis study examined the global distribution patterns of 1,780 bacteria with double or multiple carbapenemases from 277 articles and assessed their clinical impact. The presence of multiple carbapenemases increases the chances of co-resistance to other classes of antibiotics and more virulence factors, further complicating the clinical management of infections.

Research on the Migration and Adsorption Mechanism Applied to Microplastics in Porous Media: A Review.

In recent years, microplastics (MPs) have emerged as a significant environmental pollutant, garnering substantial attention for their migration and transformation behaviors in natural environments. MPs frequently infiltrate natural porous media such as soil, sediment, and rock through various pathways, posing potential threats to ecological systems and human health. Consequently, the migration and adsorption mechanisms applied to MPs in porous media have been extensively studied. This paper aims to elucidate the migration mechanisms of MPs in porous media and their influencing factors through a systematic review. The review encompasses the characteristics of MPs, the physical properties of porous media, and hydrodynamic factors. Additionally, the paper further clarifies the adsorption mechanisms of MPs in porous media to provide theoretical support for understanding their environmental behavior and fate. Furthermore, the current mainstream detection techniques for MPs are reviewed, with an analysis of the advantages, disadvantages, and applications of each technique. Finally, the paper identifies the limitations and shortcomings of current research and envisions future research directions.

Functional connectivity alterations in the thalamus among patients with bronchial asthma.

Objective: Bronchial Asthma (BA) is a common chronic respiratory disease worldwide. Earlier research has demonstrated abnormal functional connectivity (FC) in multiple cognition-related cortices in asthma patients. The thalamus (Thal) serves as a relay center for transmitting sensory signals, yet the modifications in the thalamic FC among individuals with asthma remain uncertain. This research employed the resting-state functional connectivity (rsFC) approach to explore alterations in thalamic functional connectivity among individuals with BA. Patients and methods: After excluding participants who did not meet the criteria, this study finally included 31 patients with BA, with a gender distribution of 16 males and 15 females. Subsequently, we recruited 31 healthy control participants (HC) matched for age, gender, and educational background. All participants underwent the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale (HAMD) assessment. Following this, both groups underwent head magnetic resonance imaging scans, and resting-state functional magnetic resonance imaging (rs-fMRI) data was collected. Based on the AAL (Automated Anatomical Labeling) template, the bilateral thalamic regions were used as seed points (ROI) for subsequent rsFC research. Pearson correlation analysis was used to explore the relationship between thalamic functional connectivity and neuropsychological scales in both groups. After controlling for potential confounding factors such as age, gender, intelligence, and emotional level, a two-sample t-test was further used to explore differences in thalamic functional connectivity between the two groups of participants. Result: Compared to the HC group, the BA group demonstrated heightened functional connectivity (FC) between the left thalamus and the left cerebellar posterior lobe (CPL), left postcentral gyrus (PCG), and right superior frontal gyrus (SFG). Concurrently, there was a decrease in FC with both the Lentiform Nucleus (LN) and the left corpus callosum (CC). Performing FC analysis with the right thalamus as the Region of Interest (ROI) revealed an increase in FC between the right thalamus and the right SFG as well as the left CPL. Conversely, a decrease in FC was observed between the right thalamus and the right LN as well as the left CC. Conclusion: In our study, we have verified the presence of aberrant FC patterns in the thalamus of BA patients. When compared to HCs, BA patients exhibit aberrant alterations in FC between the thalamus and various brain areas connected to vision, hearing, emotional regulation, cognitive control, somatic sensations, and wakefulness. This provides further confirmation of the substantial role played by the thalamus in the advancement of BA.

Maternal PM2.5 exposure and hypospadias risk in Chinese offspring: Insights from a nationwide surveillance-based study.

Research on the association between maternal PM2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China's National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 µg/m3 increase in maternal PM2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023-1.188) and 1.089 (95% CI: 1.007-1.177) at the 1-km grid, and 1.122 (95% CI: 1.034-1.218) and 1.143 (95% CI: 1.048-1.246) within the 6-km buffer. Higher quartiles of PM2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM2.5 exposure among expectant mothers.

Joint effects of green space and air pollutant exposure on preterm birth: evidence from a nationwide study in China.

An association between green space exposure and preterm birth has been reported. However, evidence on the joint effects of air pollutant and green space exposure on preterm birth from nationwide research is limited in China. Based on a nationwide cohort, this study aims to explore the effect of green space exposure on preterm birth and analyze the joint effects of green space and air pollutant. Logistic regression models were developed to analyze the effects of green space exposure, and interaction effects were evaluated by adding interaction terms between green space and air pollutants. From 2013 to 2019, this study included 2,294,188 records of newborn births, of which 82,921 were preterm births. The results show that for buffer zones with 250 m, 500 m, 1000 m, and 1500 m, every 0.1 unit increase in NDVI exposure was associated with a decrease in the risk of preterm birth by 5.5% (95% CI: 4.6-6.4%), 5.8% (95% CI: 4.9-6.6%), 6.1% (95% CI: 5.3-7.0%), and 5.6% (95% CI: 4.7-6.5%), respectively. Under high-level exposure to air pollutants, high-level NDVI exposure was more strongly negatively correlated with preterm birth than low-level NDVI exposure. High-level green space exposure might mitigate the adverse effect of air pollutants on preterm birth by promoting physical activity, reducing stress, and adsorbing pollutants. Further investigation is needed to explore how green space and air pollution interact and affect preterm birth, in order to improve risk management and provide a reference for newborn health.

Experimental study on the antifatigue effect of icariin.

Fatigue is a serious disturbance to human health, especially in people who have a severe disease such as cancer, or have been infected with COVID-19. Our research objective is to evaluate the anti-fatigue effect and mechanism of icariin through a mouse experimental model. Mice were treated with icariin for 30 days and anti-fatigue effects were evaluated by the weight-bearing swimming test, serum urea nitrogen test, lactic acid accumulation and clearance test in blood and the amount of liver glycogen. The protein expression levels of adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC1-α) in the skeletal muscle of mice in each group were measured by western blotting. Results showed that icariin prolonged the weight-bearing swimming time of animals, reduced the serum urea nitrogen level after exercise, decreased the blood lactic acid concentration after exercise and increased the liver glycogen content observably. Compared to that in the control group, icariin upregulated AMPK and PGC1-α expression in skeletal muscle. Icariin can improve fatigue resistance in mice and its mechanism may be through improving the AMPK/PGC-1α pathway in skeletal muscle to enhance energy synthesis, decreasing the accumulation of metabolites and slowing glycogen consumption and decomposition.

Analysis of Leaf and Soil Nutrients, Microorganisms and Metabolome in the Growth Period of Idesia polycarpa Maxim.

Idesia polycarpa Maxim is an emerging oil plant species. Understanding its microecological characteristics and internal mechanisms can serve as a basis for field management and the screening and application of growth-promoting bacteria during the growth phase of young trees. This study used three-year-old young I. polycarpa to analyze the tree's root morphology, soil, and leaf nutrient status variations from May to October. In addition, differences in the rhizosphere soil, leaf metabolites, and microorganisms were observed. The results showed that, from May to October, the total nitrogen (TN) in the soil significantly decreased, whereas the TN, total potassium (TK), and total phosphorus (TP) in the leaves differed (p < 0.05). The leaf-dominant bacteria changed from Pseudomonadota to Firmicutes phylum. In addition, the relative abundance of soil and leaf-dominant bacteria decreased. The study found that the soil and leaf differential metabolites were mainly sugars and phenolic acids. The soil bacterial community showed a significant correlation with soil pH, available potassium (AK), available phosphorus (AP), and TN (p < 0.05). Further, the soil fungal community was significantly correlated with pH and AK (p < 0.001). TP, pH, and TK were the main factors influencing the leaf bacterial community, while the leaf fungal community was significantly correlated with five factors, including pH, TC, and TN. The root morphology was also mainly affected by pH, Pedomicrobium sp., Talaromyces sp., Penicillium sp., and D-Mannitol 2.

Identification and Verification of Ferroptosis-Related Genes in Keratoconus Using Bioinformatics Analysis.

Objective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics. Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues. Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group. Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.

Strong aggregation-induced electrochemiluminescence of pyrene-coordination metal-organic frameworks coupled with zero-valent iron as novel accelerator for ultrasensitive immunoassay.

Polycyclic aromatic hydrocarbons (PAHs) are excellent alternative luminophores for electrochemiluminescence (ECL) immunoassays. However, they are inevitably limited by the aggregation-caused quenching effect. In this study, aimed at eliminating the aggregation quenching of PAHs, luminescent metal-organic frameworks (MOFs) with 1,3,6,8-tetra(4-carboxybenzene)pyrene (H4TBAPy) as the ligand were exploited as a novel nano-emitter for the construction of ECL immunoassays. The luminophore exhibits efficient aggregation-induced emission enhancement, good acid-base resistance property and unusual ECL reactivity. In addition, the simultaneous use of potassium persulfate and hydrogen peroxide as dual co-reactants resulted in a synergistic enhancement of the cathodic ECL efficiency. The use of magnetic iron-nickel alloys as the multifunctional sensing platform can further enhance the ECL activity, and its enriched zero-valent iron as a co-reactant accelerator effectively drives ECL analytical performance. Profiting from the excellent characteristics, signal-on ECL immunoassays have been constructed. With carcinoembryonic antigen as the model analysis target, a detection limit of 0.63 pg/mL was obtained within the linear range of 1 pg/mL to 50 ng/mL, accompanied by excellent analytical performance. This report opens a new window for the rational design of efficient ECL illuminators, and the proposed ECL immunoassays may find promising applications in the detection of disease markers.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

FeNi-MIL-88B-based electrochemiluminescence immunosensor for ultra-sensitive detection of CD44 protein via dual-quenching strategy.

BACKGROUND: Cluster of Differentiation 44 (CD44) is considered an important biomarker for various cancers, and achieving highly sensitive detection of CD44 is crucial, which plays a significant role in tumor invasion and metastasis, providing essential information for clinical tumor diagnosis. Commonly used methods for analysis include fluorescence spectroscopy (FL), photoelectrochemical analysis (PEC), electrochemical analysis (EC), and commercial ELISA kits. Although these methods offer high sensitivity, they can be relatively complex to perform experimentally. Electrochemiluminescence (ECL) has gained widespread research attention due to its high sensitivity, ease of operation, effective spatiotemporal control, and close to zero background signal. RESULTS: In this work, a sandwich-type ECL immunosensor for detecting CD44 was constructed using luminol as a luminophore. In this sensing platform, bimetallic MOFs (Pd@FeNi-MIL-88B) loaded with palladium nanoparticles (Pd NPs) were used as a novel enzyme mimic, exhibiting excellent catalytic performance towards the electroreduction of H2O2. The hybrids provided a strong support platform for luminol and antibodies, significantly enhancing the initial ECL signal of luminol. Subsequently, core-shell Au@MnO2 nanocomposites were synthesised by gold nanoparticles (Au NPs) encapsulated in manganese dioxide (MnO2) thin layers, as labels. In the luminol/H2O2 system, Au@MnO2 exhibited strong light absorption in the broad UV-vis spectrum, similar to the black body effect, and the scavenging effect of Mn2+ on O2•-, which achieved the dual-quenching of ECL signal. Under the optimal experimental conditions, the immunosensor demonstrated a detection range of 0.1 pg mL-1 - 100 ng mL-1, with a detection limit of 0.069 pg mL-1. SIGNIFICANCE: Based on Pd@FeNi-MIL-88B nanoenzymes and Au@MnO2 nanocomposites, a dual-quenching sandwich-type ECL immunosensor for the detection of CD44 was constructed. The proposed immunosensor exhibited excellent reproducibility, stability, selectivity, and sensitivity, and provided a valuable analytical strategy and technical platform for the accurate detection of disease biomarkers, and opened up potential application prospects for early clinical treatment.

Efficacy of the combination of BRII-196/BRII-198 in the treatment of COVID-19 vaccine breakthrough infections.

BACKGROUND: BRII-196 and BRII-198 are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. OBJECTIVE: To analyze the efficacy of BRII-196/BRII-198 in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. METHODS: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 109/L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 109/L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. RESULTS: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 109/L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with BRII-196/BRII-198. In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). CONCLUSIONS: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.