Development and validation of the PLNA score to predict cytokine storm in acute-phase SFTS patients: A single-center cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.

Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections.

The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.

MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients. Methods: The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis. Results: The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P <0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P<0.01). Discussion: For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.

Antigenicity assessment of SARS-CoV-2 saltation variant BA.2.87.1.

The recent emergence of a SARS-CoV-2 saltation variant, BA.2.87.1, which features 65 spike mutations relative to BA.2, has attracted worldwide attention. In this study, we elucidate the antigenic characteristics and immune evasion capability of BA.2.87.1. Our findings reveal that BA.2.87.1 is more susceptible to XBB-induced humoral immunity compared to JN.1. Notably, BA.2.87.1 lacks critical escaping mutations in the receptor binding domain (RBD) thus allowing various classes of neutralizing antibodies (NAbs) that were escaped by XBB or BA.2.86 subvariants to neutralize BA.2.87.1, although the deletions in the N-terminal domain (NTD), specifically 15-23del and 136-146del, compensate for the resistance to humoral immunity. Interestingly, several neutralizing antibody drugs have been found to restore their efficacy against BA.2.87.1, including SA58, REGN-10933 and COV2-2196. Hence, our results suggest that BA.2.87.1 may not become widespread until it acquires multiple RBD mutations to achieve sufficient immune evasion comparable to that of JN.1.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

A network meta-analysis on the effects of different exercise types on COPD patients.

Objective: This study aimed to compare and rank the effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in chronic obstructive pulmonary disease (COPD) by network meta-analysis (NMA).Methods: PubMed, Cochrane, Embase, and Web of Science were searched to identify randomized controlled trials investigating the effects of exercise training on COPD. The search period began on the date of database establishment and ended in April 8, 2023. Two reviewers independently screened the retrieved articles, extracted relevant data, and assessed the risk of bias in the included studies. NMA was performed using Stata 15.1 and R 4.2.1.Results: This study included a total of 27 studies involving 1415 patients. The NMA findings indicated that HIIT was the most effective intervention for improving 6-Minute Walk Distance (6MWD) with a SUCRA (Surface Under the Cumulative Ranking) score of 87.68%. In addition, HIIT showed the highest efficacy in improving Forced Expiratory Volume in 1 second (FEV1) with a SUCRA score of 73.17%, FEV1/FVC% with a SUCRA score of 79.52%, and St. George's Respiratory Questionnaire (SGRQ) score with a SUCRA score of 73.88%. Conversely, ET was found to be the most effective for ameliorating Forced Vital Capacity (FVC) with a SUCRA score of 73.39%.Conclusion: The findings of this study suggest that HIIT may be more effective than endurance exercise, resistance exercise, and AE in improving the 6MWD, FEV1, FEV1/FVC ratio, and SGRQ scores in patients with COPD. Additionally, ET may be better than resistance exercise, AE, and HIIT in improving FVC in COPD patients. However, due to the limited number of studies conducted on HIIT, more high-quality randomized controlled trials (RCTs) are required to verify these conclusions.

Stretchable structural colors with polarization dependence using lithium niobate metasurfaces.

Independently tunable biaxial color pixels, composed of isolated nanosquare dimers, are demonstrated in this study. These pixels are capable of displaying a full range of colors under a linear-polarization dependent reflection mode. The metasurface is constructed by arranging LiNbO3 nanodimers on a PDMS substrate. By exciting a strong magnetic dipole (MD) resonance and effectively suppressing other multipolar resonances using surface lattice resonances, the researchers achieved a single reflection peak with a bandwidth of less than 9 nm and a reflective efficiency of up to 99%. Additionally, the stretchability of the PDMS substrate allows for active and continuous tuning of the metasurface by up to 40% strain, covering almost 150 nm of the visible light spectrum and enabling changes in reflection color. This metasurface holds potential applications in various fields, such as color displays, data storage, and anti-counterfeiting technologies.

Visible-Light-Promoted Selenylation/Cyclization of o-Alkynyl Benzylazides/o-Propargyl Arylazides: Synthesis of Seleno-Substituted Isoquinolines and Quinolines.

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

Selective Aza-Michael Addition to Dehydrated Amino Acids in Natural Antimicrobial Peptides.

We report the efficient and site selective modification of non-canonical dehydroamino acids in ribosomally synthesized and post-transationally modified peptides (RiPPs) by ß-amination. The singly modified thiopeptide Thiostrepton showed an up to 35-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity remained good, albeit lower than the unmodified peptide. Also the lanthipeptide nisin could be modified using this method.

Instability, changes, and internal structure of children's attitudes toward mathematics in primary school: A four-wave investigation.

The longitudinal person-oriented study aimed to explore profiles, stability, gender differences, and compositional relations of math attitudes by tracking Chinese third graders (Ntotal = 1013, Mage(T1) = 8.92 ± 0.46, Ngirls = 404) in four waves with 1-year intervals. Five profiles and unstable transitional probabilities were identified among the four waves. The relations between enjoyment to confidence and value shifted from reciprocity to enjoyment dominance, but value negatively predicted later enjoyment and confidence. Additionally, boys' advantages were significant in late elementary school (fifth, sixth grades) and girls benefited from initial positive attitudes. These findings suggest that Chinese students' math attitudes in middle childhood are unstable, shaped by internal and external environmental dynamics, and need to be further explored in cross-cultural research.

Transcriptomic analysis of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with testicular size in Hu sheep.

Testicular size is an excellent proxy for selecting high-fertility rams. The hypothalamus-pituitary-gonadal (HPG) axis plays an important role in regulating reproductive capacity in vertebrates, while key genes and regulatory pathways within the HPG axis associated with testicular size remain largely unknown in sheep. This study comprehensively compared the transcriptomic profiles in the hypothalamus, pituitary and testis of rams after sexual maturity between the large-testis group (LTG, testicular weight = 454.29 ± 54.24 g) and the small-testis group (STG, testicular weight = 77.29 ± 10.76 g). In total, 914, 795 and 10518 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary and testis between LTG and STG, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly involved in the biological processes of reproduction, biological regulation, and development process. Notably, the neuroactive ligand-receptor interaction and cAMP signaling pathways, commonly enriched by the DEGs in the hypothalamus and pituitary between two groups, were considered as two key signal pathways regulating testicular development through the HPGs axis. Weighted gene co-expression network analysis (WGCNA) identified two modules that were significantly associated with testicular size, and 97 key genes were selected with high module membership (MM) and gene significance (GS) in these two modules. Finally, a protein-protein interaction (PPI) network was constructed, and ten genes with the highest degree were represented as hub genes, including FOS, NPY, SST, F2, AGT, NTS, OXT, EDN1, VIP and TAC1. Taken together, these results provide new insights into the molecular mechanism underlying the HPG axis regulating testicular size of Hu sheep.

Phthalates contamination in sediments: A review of sources, influencing factors, benthic toxicity, and removal strategies.

Sediments provide habitat and food for benthos, and phthalates (PAEs) have been detected in numerous river and marine sediments as a widely used plastic additive. PAEs in sediments is not only toxic to benthos, but also poses a threat to pelagic fish and human health through the food chain, so it is essential to comprehensively assess the contamination of sediments with PAEs. This paper presents a critical evaluation of PAEs in sediments, which is embodied in the analysis of the sources of PAEs in sediments from multiple perspectives. Biological production is indispensable, while artificial synthesis is the most dominant, thus the focus was on analyzing the industrial and commercial sources of synthetic PAEs. In addition, since the content of PAEs in sediments varies, some factors affecting the content of PAEs in sediments are summarized, such as the properties of PAEs, the properties of plastics, and environmental factors (sediments properties and hydrodynamic conditions). As endocrine disruptors, PAEs can produce toxicity to its direct contacts. Therefore, the effects of PAEs on benthos immunity, endocrinology, reproduction, development, and metabolism were comprehensively analyzed. In addition, we found that reciprocal inhibition and activation of the systems lead to genotoxicity and apoptosis. Finally, the paper discusses the feasible measures to control PAEs in wastewater and leachate from the perspective of source control, and summarizes the in-situ treatment measures for PAEs contamination in sediments. This paper provides a comprehensive review of PAEs contamination in sediments, toxic effects and removal strategies, and provides an important reference for reducing the contamination and toxicity of PAEs to benthos.

Foretinib Is Effective in Acute Myeloid Leukemia by Inhibiting FLT3 and Overcoming Secondary Mutations That Drive Resistance to Quizartinib and Gilteritinib.

FLT3 internal tandem duplication (FLT3-ITD) mutations are one of the most prevalent somatic alterations associated with poor prognosis in patients with acute myeloid leukemia (AML). The clinically approved FLT3 kinase inhibitors gilteritinib and quizartinib improve the survival of patients with AML with FLT3-ITD mutations, but their long-term efficacy is limited by acquisition of secondary drug-resistant mutations. In this study, we conducted virtual screening of a library of 60,411 small molecules and identified foretinib as a potent FLT3 inhibitor. An integrated analysis of the BeatAML database showed that foretinib had a lower IC50 value than other existing FLT3 inhibitors in patients with FLT3-ITD AML. Foretinib directly bound to FLT3 and effectively inhibited FLT3 signaling. Foretinib potently inhibited proliferation and promoted apoptosis in human AML cell lines and primary AML cells with FLT3-ITD mutations. Foretinib also significantly extended the survival of mice bearing cell-derived and patient-derived FLT3-ITD xenografts, exhibiting stronger efficacy than clinically approved FLT3 inhibitors in treating FLT3-ITD AML. Moreover, foretinib showed potent activity against secondary mutations of FLT3-ITD that confer resistance to quizartinib and gilteritinib. These findings support the potential of foretinib for treating patients with AML with FLT3-ITD mutations, especially for those carrying secondary mutations after treatment failure with other FLT3 inhibitors. SIGNIFICANCE: Foretinib exhibits superior efficacy to approved drugs in AML with FLT3-ITD mutations and retains activity in AML with secondary FLT3 mutations that mediate resistance to clinical FLT3 inhibitors.

Direct determination of high-concentration As(III) by UV high-reference differential absorption spectroscopy for cleaner As(III) removal promotion via sulfurization.

The current methods for determining high-concentration As(III) in the high-acid matrix from the copper smelting industry are complex, time-consuming, and costly. This limits effective modulation of sulfurizing agent dosage for As(III) removal via sulfurization, aggravating hazardous waste generation. Herein, a simple, rapid, and nondestructive UV high-reference differential absorption spectroscopy was developed to directly determine high-concentration As(III) in simulated high-acid wastewater. Time-dependent density functional theory calculations indicated that the spectral curve redshift with As(III) concentration increasing was related to the decrease of electron transition energies and energy gaps. When using high-reference solutions, the least redshift in the maximum absorption wavelength and the highest upper limit of linear fitting concentration could be obtained. Therefore, the piecewise quantitative linear model of differential absorbance and concentration was established under high-reference. The quantitative range of the model within 0.06-20.00 g/L As(III) with a mean relative error of < 5.0 % and standard recovery rates within 98.0 %-104.0 % indicated high accuracy. Additionally, the relative standard deviations of < 1.5 % (n = 5) revealed good precision. All results indicated the high feasibility of the developed method in alleviating linear deviation caused by redshift and absorption saturation. Furthermore, it has potential significance in saving sulfurizing agent dosage and reducing hazardous waste generation from the source, thereby facilitating a cleaner process for removing As(III) via sulfurization.

Math attitudes and math anxiety predict students' perception of teacher support in primary school, but not vice versa.

BACKGROUND: Both teacher support and math attitudes have been identified as associated with math anxiety in primary school children. However, little is known about how they are interrelated longitudinally. AIMS: The study was designed to examine the associations among perceived teacher support, math attitudes, and math anxiety in Chinese primary school students. SAMPLE: The sample included 1802 students (56.16% boys) initially in the third and fourth grades in two public schools in China. METHODS: A three-year cross-lagged panel design was conducted to examine the associations among perceived teacher support, math attitudes, and math anxiety. Moreover, a multigroup analysis was used to examine whether the associations varied by gender. RESULTS: There were reciprocal associations over time between math attitudes and math anxiety. Meanwhile, both math attitudes and math anxiety significantly predicted perceived teacher support one year later, but not vice versa. Further, the association between T1 math anxiety and T3 perceived teacher support was mediated by T2 math attitudes; the association between T1 math attitudes and T3 perceived teacher support, on the other hand, was mediated by T2 math anxiety. Moreover, there were no significant gender differences in these associations. CONCLUSIONS: Math anxiety and math attitudes objectively affected each other, and both of them significantly predicted later perceived teacher support, but not vice versa. This study demonstrates that children are not merely passive recipients of environmental influences and offers theoretical guidance for intervention practices that aim to reduce the risk of math anxiety.

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1-5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT-such as the XBB variant-and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.

Tissue-specific toxic effects of nano-copper on zebrafish.

Understanding the behavior and potential toxicity of copper nanoparticles (nano-Cu) in the aquatic environment is a primary way to assess their environmental risks. In this study, RNA-seq was performed on three different tissues (gills, intestines, and muscles) of zebrafish exposed to nano-Cu, to explore the potential toxic mechanism of nano-Cu on zebrafish. The results indicated that the toxic mechanism of nano-Cu on zebrafish was tissue-specific. Nano-Cu enables the CB1 receptor of the presynaptic membrane of gill cells to affect short-term synaptic plasticity or long-term synaptic changes (ECB-LTD) through DSI and DSE, causing dysfunction of intercellular signal transmission. Imbalance of de novo synthesis of UMP in intestinal cells and its transformation to UDP, UTP, uridine, and uracil, resulted in many functions involved in the pyrimidine metabolic pathway being blocked. Meanwhile, the toxicity of nano-Cu caused abnormal expression of RAD51 gene in muscle cells, which affects the repair of damaged DNA through Fanconi anemia and homologous recombination pathway, thus causing cell cycle disorder. These results provide insights for us to better understand the differences in toxicity of nano-Cu on zebrafish tissues and are helpful for a comprehensive assessment of nano-Cu's effects on aquatic organisms.

A critical review on BDE-209: Source, distribution, influencing factors, toxicity, and degradation.

As the most widely used polybrominated diphenyl ether, BDE-209 is commonly used in polymer-based commercial and household products. Due to its unique physicochemical properties, BDE-209 is ubiquitous in a variety of environmental compartments and can be exposed to organisms in various ways and cause toxic effects. The present review outlines the current state of knowledge on the occurrence of BDE-209 in the environment, influencing factors, toxicity, and degradation. BDE-209 has been detected in various environmental matrices including air, soil, water, and sediment. Additionally, environmental factors such as organic matter, total suspended particulate, hydrodynamic, wind, and temperature affecting BDE-209 are specifically discussed. Toxicity studies suggest BDE-209 may cause systemic toxic effects on living organisms, reproductive toxicity, embryo-fetal toxicity, genetic toxicity, endocrine toxicity, neurotoxicity, immunotoxicity, and developmental toxicity, or even be carcinogenic. BDE-209 has toxic effects on organisms mainly through epigenetic regulation and induction of oxidative stress. Evidence regarding the degradation of BDE-209, including biodegradation, photodegradation, Fenton degradation, zero-valent iron degradation, chemical oxidative degradation, and microwave radiation degradation is summarized. This review may contribute to assessing the environmental risks of BDE-209 to help develop rational management plans.

Simultaneous occurrence of multiple myeloma and acute myeloid leukemia: Case report and literature review.

Multiple myeloma (MM) and acute myeloid leukemia (AML) are malignant clonal diseases of cells in different lineages. It remains very rare to have both diseases at first diagnosis. Only 24 cases of this situation were reported from 1971 to 2021, and poor prognosis in most cases. However, here we describe a case of de novo MM and AML occurring simultaneously in a 65-year-old woman. We have successfully used individualized treatment regimens to allow the patient to survive 1.5 years to date, which has exceeded 80 % of statistical cases.