Fluorinated plant activators induced dual-pathway signal transduction and long-lasting ROS burst in chloroplast.

Synthetic plant activators represent a promising novel class of green pesticides that can triggering endogenous plant immunity against pathogen invasion. In our previous study, we developed a series of fluorinated compounds capable of eliciting disease resistance in plants; however, the underlying regulatory mechanisms remained unclear. In this study, we systematically investigated the mechanism of plant immune activation using four synthetic plant activators in Arabidopsis thaliana (A. thaliana), including two fluorine-substituted and two non­fluorine-substituted molecules. Our findings revealed that the fluorinated compounds exhibited superior disease resistance activity compared to the non-fluorinated molecules. Gene expression analysis in systemic acquired resistance (SAR)- and induced systemic resistance (ISR)-related pathways demonstrated that fluorine substitution effectively regulated both SAR- and ISR-pathway activation, highlighting the distinct roles of fluorine in modulating the plant immune system. Notably, the prolonged ROS burst was observed in chloroplasts following treatment with all four plant activators, contrasting with the transient ROS burst induced by natural elicitors. These results provide insights into the unique mechanisms underlying synthetic plant activator-induced plant immunity. Furthermore, comprehensive proteomic analysis revealed a robust immune response mediated by fluorine-substituted plant activators. These findings offer novel insights into the role of fluorine substitution in SAR- and ISR-associated immune signaling pathways and their distinct impact on ROS production within chloroplasts.

Differential utilization of vitamin B12-dependent and independent pathways for propionate metabolism across human cells.

Propionic acid links the oxidation of branched-chain amino acids and odd-chain fatty acids to the TCA cycle. Gut microbes ferment complex fiber remnants, generating high concentrations of short chain fatty acids, acetate, propionate and butyrate, which are shared with the host as fuel sources. Analysis of vitamin B12-dependent propionate utilization in skin biopsy samples has been used to characterize and diagnose underlying inborn errors of cobalamin (or B12) metabolism. In these cells, the B12-dependent enzyme, methylmalonyl-CoA mutase (MMUT), plays a central role in funneling propionate to the TCA cycle intermediate, succinate. Our understanding of the fate of propionate in other cell types, specifically, the involvement of the ß-oxidation-like and methylcitrate pathways, is limited. In this study, we have used [14C]-propionate tracing in combination with genetic ablation or inhibition of MMUT, to reveal the differential utilization of the B12-dependent and independent pathways for propionate metabolism in fibroblast versus colon cell lines. We demonstrate that itaconate can be used as a tool to investigate MMUT-dependent propionate metabolism in cultured cell lines. While MMUT gates the entry of propionate carbons into the TCA cycle in fibroblasts, colon-derived cell lines exhibit a quantitatively significant or exclusive reliance on the ß-oxidation-like pathway. Lipidomics and metabolomics analyses reveal that propionate elicits pleiotropic changes, including an increase in odd-chain glycerophospholipids, and perturbations in the purine nucleotide cycle and arginine/nitric oxide metabolism. The metabolic rationale and the regulatory mechanisms underlying the differential reliance on propionate utilization pathways at a cellular, and possibly tissue level, warrant further elucidation.

Bidirectional Mendelian randomization to explore the causal relationships between the gut microbiota and male reproductive diseases.

Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.

[Spatiotemporal Distribution Characteristics of Ground-level-ozone and Its Relationship with Meteorological Conditions in a Representative City in the Bohai Rim from 2017 to 2022].

In recent years, ground-level-ozone（O3） pollution in urban areas in the Bohai Rim has attracted wide attention. Based on the analysis of the spatiotemporal distribution characteristics of O3 concentration in Dongying, a representative city in the Bohai Rim from 2017 to 2022, the effects of meteorological factors and sea-land breeze circulation on O3 concentration were evaluated. The results showed that： ① From 2017 to 2022, the annual assessment value of O3 concentration in Dongying showed a fluctuating upward trend, and the pollution days with O3 as the primary pollutant increased. O3 pollution mainly occurred in spring, summer, and autumn, with the most severe O3 pollution episodes typically occurring in May and June, and the duration of O3 pollution season tended to be longer. The monthly variation in the daily maximum 8-h average ozone （MDA8 O3） presented a bimodal distribution, with significant increases in the 5th and 25th percentiles, and the spatial distribution was "high in the north and south, low in the middle." In addition, the nocturnal O3 concentration in recent years in Dongying also showed a significant increase trend. ② Meteorological factors greatly influenced O3 concentration in Dongying. When the temperature was greater than 30℃, the relative humidity was less than 50%, and the wind direction was south-southwest or east-northeast, a high O3 value was more likely to occur. Meteorological factors contributed 30% of the MDA8 O3 variation in Dongying during the study period. In the case of moderate and severe O3 pollution, the contribution of meteorological factors to the change in MDA8 O3 could be as high as 40%. ③ To some extent, sea-land breeze contributed to the occurrence of MDA8 O3 exceeding the secondary standard limit value of the National Ambient Air Quality Standard. In the afternoon, the hourly concentration of O3 during the sea-land breeze days was approximately 20 µg·m-3 higher than that during the non-sea-land breeze days. On the days of moderate and severe O3 pollution, the O3 concentration during the sea-land breeze days from 10：00 to 16：00 was higher than that during non-sea-land breeze days, and the O3 concentration was also at a high level from 20：00 to 23：00 on sea-land breeze days. In the O3 pollution season, the sea-land breeze could significantly affect the O3 level in coastal cities, which could bring significant challenges for O3 pollution prevention and control in this region. In the future, cities in the Bohai Rim need to further strengthen regional joint prevention and control of O3 pollution and increase emission reduction efforts of nitrogen oxides and volatile organic compounds. This strategy could effectively lower pollutant concentrations within the land breeze air mass, consequently reducing the impact of the sea breeze air mass on air quality in cities in the Bohai Rim.

Understanding grain development in the Poaceae family by comparing conserved and distinctive pathways through omics studies in wheat and maize.

The Poaceae family, commonly known as the grass family, encompasses a diverse group of crops that play an essential role in providing food, fodder, biofuels, environmental conservation, and cultural value for both human and environmental well-being. Crops in Poaceae family are deeply intertwined with human societies, economies, and ecosystems, making it one of the most significant plant families in the world. As the major reservoirs of essential nutrients, seed grain of these crops has garnered substantial attention from researchers. Understanding the molecular and genetic processes that controls seed formation, development and maturation can provide insights for improving crop yield, nutritional quality, and stress tolerance. The diversity in photosynthetic pathways between C3 and C4 plants introduces intriguing variations in their physiological and biochemical processes, potentially affecting seed development. In this review, we explore recent studies performed with omics technologies, such as genomics, transcriptomics, proteomics and metabolomics that shed light on the mechanisms underlying seed development in wheat and maize, as representatives of C3 and C4 plants respectively, providing insights into their unique adaptations and strategies for reproductive success.

Spinal cord injury disrupts plasma extracellular vesicles cargoes leading to neuroinflammation in the brain and neurological dysfunction in aged male mice.

Aged individuals with spinal cord injury (SCI) are prevalent with increased mortality and worse outcomes. SCI can cause secondary brain neuroinflammation and neurodegeneration. However, the mechanisms contributing to SCI-induced brain dysfunction are poorly understood. Cell-to-cell signaling through extracellular vesicles (EVs) has emerged as a critical mediator of neuroinflammation, including at a distance through circulation. We have previously shown that SCI in young adult (YA) male mice leads to robust changes in plasma EV count and microRNAs (miRs) content. Here, our goal was to investigate the impact of old age on EVs and brain after SCI. At 24 h post-injury, there was no difference in particle count or size distribution between YA and aged mice. However, aged animals increased expression of EV marker CD63 with SCI. Using the Fireplex® miRs assay, Proteomics, and mass spectrometry-based Lipidomics, circulating EVs analysis identified distinct profiles of miRs, proteins, and lipid components in old and injury animals. In vitro, plasma EVs from aged SCI mice, at a lower concentration comparable to those of YA SCI mice, induced the secretion of pro-inflammatory cytokines and neuronal apoptosis. Systemic administration of plasma EVs from SCI animals was sufficient to impair general physical function and neurological function in intact animals, which is associated with pro-inflammatory changes in the brain. Furthermore, plasma EVs from young animals had rejuvenating effects on naïve aged mice. Collectively, these studies identify the critical changes in circulating EVs cargoes after SCI and in aged animals and support a potential EV-mediated mechanism for SCI-induced brain changes.

Cofitness network connectivity determines a fuzzy essential zone in open bacterial pangenome.

Most in silico evolutionary studies commonly assumed that core genes are essential for cellular function, while accessory genes are dispensable, particularly in nutrient-rich environments. However, this assumption is seldom tested genetically within the pangenome context. In this study, we conducted a robust pangenomic Tn-seq analysis of fitness genes in a nutrient-rich medium for Sinorhizobium strains with a canonical open pangenome. To evaluate the robustness of fitness category assignment, Tn-seq data for three independent mutant libraries per strain were analyzed by three methods, which indicates that the Hidden Markov Model (HMM)-based method is most robust to variations between mutant libraries and not sensitive to data size, outperforming the Bayesian and Monte Carlo simulation-based methods. Consequently, the HMM method was used to classify the fitness category. Fitness genes, categorized as essential (ES), advantage (GA), and disadvantage (GD) genes for growth, are enriched in core genes, while nonessential genes (NE) are over-represented in accessory genes. Accessory ES/GA genes showed a lower fitness effect than core ES/GA genes. Connectivity degrees in the cofitness network decrease in the order of ES, GD, and GA/NE. In addition to accessory genes, 1599 out of 3284 core genes display differential essentiality across test strains. Within the pangenome core, both shared quasi-essential (ES and GA) and strain-dependent fitness genes are enriched in similar functional categories. Our analysis demonstrates a considerable fuzzy essential zone determined by cofitness connectivity degrees in Sinorhizobium pangenome and highlights the power of the cofitness network in understanding the genetic basis of ever-increasing prokaryotic pangenome data.

Development and evaluation of a liquid chromatography-tandem mass spectrometry method for simultaneous measurement of toxic aldehydes from brain tissue.

Reactive aldehydes are a class of electrophilic low molecular weight compounds that play an essential role in physiological function and lipid peroxidation. These molecules are implicated in many diseases, especially cardiovascular and neurodegenerative diseases, and are potential endogenous markers of lipid peroxidation. However, there are limited options to accurately quantify multiple reactive aldehydes in brain tissue. This study developed and validated a 3-nitrophenylhydrazine derivatization-based LC-MS/MS method to quantify four reactive aldehydes: malondialdehyde, acrolein, 4-hydroxy-2-hexenal and 4-hydroxy-2-nonenal. Method development involved comparing the sensitivity of detection between widely used derivatization reagents: 2,4-dinitrophenylhydrazine and 3-nitrophenylhydrazine. Our data showed that 3-nitrophenylhydrazine resulted in greater sensitivity. Additional method development included evaluation of hydrolysis sample pretreatment, selection of protein precipitation reagent, and optimization of derivatization conditions. The optimized conditions included no hydrolysis and use of 20 % trichloroacetic acid as the protein precipitation reagent. The optimized derivatization condition was 25 mM 3-nitrophenylhydrazine reacted at 20 °C for 30 min. The chromatographic conditions were optimized to reduce matrix effects, ion suppression, and efficient analysis time (<7-minute analytical run). The four aldehyde species were accurately quantified in brain tissue using stable-labeled internal standards. Application of this assay to a traumatic brain injury mouse model revealed significant accumulation of acrolein, 4-hydroxy-2-hexenal, and 4-hydroxy-2-nonenal at 28 days post injury. Overall, a validated method was developed to rapidly quantify the most prominent reactive aldehydes associated with lipid peroxidation during injury progression following acute brain trauma.

Metabolomic and chemometric analyses of St. John's wort and related Asian Hypericum species linked to bioactivity.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants in the genus Hypericum (Hypericaceae), include more than 500 species worldwide, and many are valued for their medicinal properties, and are used as traditional herbal medicines. However, only H. perforatum is officially recognized as herbal drug in several pharmacopoeias, and used as an antidepressant clinically. Hypericum perforatum had been used as an herbal medicine since the Han Dynasty (206 B.C. -220 A.D.) in China. It taxonomically belongs to the section Hypericum in the genus Hypericum. There are about 42 species in the section Hypericum, with six species occurring in China. All six are recorded as traditional herbal medicines for treating aliments, including hepatitis, malaria, traumatic hemorrhage, irregular menstruation, wounds, and bruises. AIM OF THE STUDY: The study aimed to characterize the chemical profiles of five phylogenetically related Hypericum species, and compare their metabolites with three H. perforatum products. Informed by ethnobotanical use, the extracts prepared from the five species were further investigated into anticancer, anti-inflammatory and antiplasmodial activity. This study tested the hypothesis that systematic metabolomic and bioactivity characterization of species in section Hypericum will help to validate their phytotherapeutic use and reveal potential drug lead compounds. MATERIALS AND METHODS: Targeted and non-targeted metabolic analyses coupled with chemometrics were conducted on H. perforatum and four medicinal species, H. attenuatum, H. enshiense, H. erectum, and H. faberi, native to China from section Hypericum. UPLC-QTOF-MS/MS and UPLC-TQD-MS/MS were used for non-targeted and targeted metabolic analyses, respectively. Cytotoxicity bioassays on four cancer cell lines, anti-inflammation tests and anti-plasmodial activity on Plasmodium falciparum 3D7, selected based on traditional medicinal use, were evaluated on extracts from Hypericum species. Progenesis QI and EZinfo were used for chemometrics analysis to link the chemical profile and bioassay activity to aid in the identification of bioactive compounds. RESULTS: In total, 58 compounds were identified from the five species, including compounds with well-characterized bioactivity. Hypericum attenuatum, H. erectum, and H. perforatum, displayed the highest cytotoxicity, and contain the cytotoxic compounds petiolin A, prolificin A, and hypercohin G, respectively. Hypericum faberi and H. perforatum showed the highest anti-inflammatory activity, with pseudohypericin, quercetin and chlorogenic acid being observed at higher concentrations. Hypericum perforatum and H. erectum showed anti-plasmodial activity, with higher hyperforin and xanthones in these species that may account for the anti-plasmodial activity. CONCLUSIONS: This study characterized the chemical differences among five Hypericum species using metabolomics. These ethnomedically important species were tested for their biological activities in three distinct in vitro assays. The ethnobotanical data were useful for identifying bioactive Hypericum species. Hypericum attenuatum, H. erectum and H. faberi are promising phytotherapeutic species, although they are much less studied than H. perforatum, St. John's wort. Combining ethnobotanical surveys with chemometric analyses and bioactivity screening can greatly enhance the discovery of promising active constituents.

Activity Limitations and Depression Among Middle-Aged and Older Adults in China: The Moderating Impact of Assistance Adequacy.

This study aimed to examine the risk and protective factors associated with depression in middle-aged and older Chinese adults with activity limitations. Data were obtained from the 2018 Wave 4 Survey of the China Health and Retirement Longitudinal Study. In the logistic regression analysis, health and functioning, losing a child, and a perceived lack of future assistance with daily activities increased the odds of depression. Conversely, receiving adequate assistance with daily activities lessened the depressive impacts of activity limitations, as indicated by a significant interaction effect. Enhanced long-term support for individuals with disabilities is necessary to improve mental health.

Transcriptome-Based Identification of the SaR2R3-MYB Gene Family in Sophora alopecuroides and Function Analysis of SaR2R3-MYB15 in Salt Stress Tolerance.

As one of the most prominent gene families, R2R3-MYB transcription factors significantly regulate biochemical and physiological processes under salt stress. However, in Sophora alopecuroides, a perennial herb known for its exceptional saline alkali resistance, the comprehensive identification and characterization of SaR2R3-MYB genes and their potential functions in response to salt stress have yet to be determined. We investigated the expression profiles and biological functions of SaR2R3-MYB transcription factors in response to salt stress, utilizing a transcriptome-wide mining method. Our analysis identified 28 SaR2R3-MYB transcription factors, all sharing a highly conserved R2R3 domain, which were further divided into 28 subgroups through phylogenetic analysis. Some SaR2R3-MYB transcription factors showed induction under salt stress, with SaR2R3-MYB15 emerging as a potential regulator based on analysis of the protein-protein interaction network. Validation revealed the transcriptional activity and nuclear localization of SaR2R3-MYB15. Remarkably, overexpression of SaR2R3-MYB15 in transgenic plants could increase the activity of antioxidant enzymes and the accumulation of proline but decrease the content of malondialdehyde (MDA), compared with wild-type plants. Moreover, several salt stress-related genes showed higher expression levels in transgenic plants, implying their potential to enhance salt tolerance. Our findings shed light on the role of SaR2R3-MYB genes in salt tolerance in S. alopecuroides.

Geriatric nutritional risk index is correlated with islet function but not insulin resistance in elderly patients with type 2 diabetes: A retrospective study.

The geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that can predict poor prognosis in elderly subjects. The aim of this study was to evaluate the association between GNRI and both islet function and insulin sensitivity in patients with type 2 diabetes mellitus. This research carries significant implications for the integrated treatment and nutritional management of this patient population. A total of 173 patients with type 2 diabetes mellitus, aged 60 years or older, who were hospitalized in the Endocrinology Department at Hebei General Hospital from February 2018 to June 2021, were selected as the research subjects. These subjects were divided into 4 groups according to the quartile of their GNRI values: T1 (GNRI < 99.4, n = 43), T2 (99.4 ≤ GNRI < 103, n = 43), T3 (103 ≤ GNRI < 106.3, n = 43), and T4 (GNRI ≥ 106.3, n = 44). Glucose, insulin, and C-peptide concentrations were tested at 0, 30, 60, 120, and 180 minutes during a 75 g oral glucose tolerance test. The homeostasis model assessment for insulin resistance and the homeostasis model assessment for ß cell function index were calculated. As the GNRI value increased, the levels of total protein, albumin, hemoglobin, alanine transaminase, aspartate aminotransferase, and 25-hydroxyvitamin D increased significantly. The area under the curve for blood glucose decreased significantly across the 4 groups, while the AUCs for insulin and C-peptide showed an overall increasing trend. ß Cell function index increased significantly with the increase of GNRI; meanwhile, both the early-phase insulin secretion index and the late-phase insulin secretion index increased significantly. Although there was an increasing trend, homeostasis model assessment for insulin resistance did not change significantly among the 4 groups. This study indicates that elderly type 2 diabetes patients with higher nutritional risk have worse islet function, while insulin sensitivity is not associated with nutritional risk.

Novel role of lncRNAs regulatory network in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The incidence of PTC has increased annually worldwide. Thus, PTC diagnosis and treatment attract more attention. Noncoding RNAs (lncRNAs) play crucial roles in PTC progression and act as prognostic biomarkers. Moreover, microRNAs (miRNAs) and epithelial-mesenchymal transition (EMT)-associated proteins have potential biomarkers for diagnosing and treating PTC. However, the correlation of lncRNAs with miRNAs and EMT-associated proteins needs further clarification. The present review highlights the recent advances of lncRNAs in PTC. We significantly summarized the two molecular regulatory mechanisms in PTC progress, including lncRNAs-miRNAs-protein signaling axes and lncRNAs-EMT pathways. This review will help our understanding of the association between lncRNAs and PTC and may assist us in evaluating the prognosis for PTC patients. Taken together, targeting the lncRNAs regulatory network has promising applications in diagnosing and treating PTC.

A review on nocturnal surface ozone enhancement: Characterization, formation causes, and atmospheric chemical effects.

In recent years, the frequent occurrence of nocturnal background ozone enhancement (A gradually increasing trend in the long-term change of nocturnal ozone concentration, [NBOE]) and nocturnal ozone enhancement (the presence of a nocturnal ozone peak and high nocturnal ozone value, [NOE]) have attracted extensive attention in the academic community. NBOE and NOE impact atmospheric chemical processes, and higher nocturnal ozone concentrations adversely affect human health and biological growth. Therefore, we reviewed the research history of NBOE and NOE, provided an overview of research on NBOE, and summarized the spatiotemporal distribution characteristics of NOE. According to the available observations, the frequency of NOE in a long-time series (i.e., more than one year) from 2005 to 2020 generally ranges between 15 % and 50 %. Compared to other nations, China has a higher nocturnal ozone peak. In most NOE events, the magnitude of ozone increase (ΔO3/Δt) ranges from 5 to 20 ppb, and NOE events occur more frequently during midnight. In addition, we described the current international-level understanding of the causes of NOE and the impact of NOE on nighttime and next-day atmospheric chemical processes. Future research should not only enhance the quantitative analysis of the causal factors of NBOE and NOE, but also prioritize exploring how NBOE and NOE influence secondary pollutant production, human health, and biological growth. Finally, attention should be paid to the influence of NBOE and NOE on the formulation of synergistic control policies for PM2.5 and ozone.

Artificial neural network for deciphering the structural transformation of condensed ZnO by extended x-ray absorption fine structure spectroscopy.

Pressure-induced structural phase transitions play a pivotal role in unlocking novel material functionalities and facilitating innovations in materials science. Nonetheless, unveiling the mechanisms of densification, which relies heavily on precise and comprehensive structural analysis, remains a challenge. Herein, we investigated the archetypalB4 →B1 phase transition pathway in ZnO by combining x-ray absorption fine structure (XAFS) spectroscopy with machine learning. Specifically, we developed an artificial neural network (NN) to decipher the extended-XAFS spectra by reconstructing the partial radial distribution functions of Zn-O/Zn pairs. This provided us with access to the evolution of the structural statistics for all the coordination shells in condensed ZnO, enabling us to accurately track the changes in the internal structural parameteruand the anharmonic effect. We observed a clear decrease inuand an increased anharmonicity near the onset of theB4 →B1 phase transition, indicating a preference for the iT phase as the intermediate state to initiate the phase transition that can arise from the softening of shear phonon modes. This study suggests that NN-based approach can facilitate a more comprehensive and efficient interpretation of XAFS under complexin-situconditions, which paves the way for highly automated data processing pipelines for high-throughput and real-time characterizations in next-generation synchrotron photon sources.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Dynamic monitoring of neutrophil/lymphocyte ratio, APACHE II score, and SOFA score predict prognosis and drug resistance in patients with Acinetobacter baumannii-calcoaceticus complex bloodstream infection: a single-center retrospective study.

Objective: This study aimed to evaluate the clinical value of dynamic monitoring of neutrophil/lymphocyte ratio (NLR), APACHE II (Acute Physiology and Chronic Health Evaluation II) score, and Sequential Organ Failure Assessment (SOFA) score in predicting 28-day prognosis and drug resistance in patients with bloodstream infection with Acinetobacter baumannii-calcoaceticus complex (Abc complex). Patients and methods: In this research, individuals admitted to Tianjin Medical University General Hospital from January 2017 to March 2023 with bloodstream infections and a minimum of one Abc complex positive blood culture were chosen. The risk factors for the 28-day prognosis and drug resistance were analyzed using logistic regression. The NLR, APACHE II score, and SOFA score were evaluated for predicting 28-day prognosis and drug resistance using an ROC curve analysis. The data were analyzed using R Studio to find correlations and conduct survival analysis with the Kaplan-Meier method. Results: The final statistical analysis included a total of 129 patients with bloodstream infections caused by Abc complex. Independent risk factors predicting mortality within 28 days were identified as follows: the SOFA score and APACHE II scores at 24 h, and APACHE II scores at 72 h after the onset of blood infection (p < 0.05). NLR, SOFA score, and APACHE II score did not predict drug resistance. Patients with Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) had shorter survival times than those with carbapenem-sensitive strains (40.77 days vs. 47.65 days, respectively, p = 0.0032). Conclusion: The prognosis of Abc complex bloodstream infection is affected by both SOFA and APACHE II scores. Both scoring systems have similar prognostic values at different time points after infection, but for computational convenience, it is recommended to use the SOFA score. NLR exhibits limited effectiveness in predicting mortality within 28 days. Carbapenem-resistant individuals with Abc complex experience significantly reduced survival time. None of the three factors-SOFA score, APACHE II score, and NLR-can early predict the occurrence of CRAB infections effectively.

Immunogenicity of an adenovirus-vectored bivalent vaccine against wild type SARS-CoV-2 and Omicron variants in a murine model.

BACKGROUND: The emergence and rapid spread of new mutant strains of SARS-CoV-2 necessitate the development of a new generation vaccine capable of neutralizing a broad range of variants. When the SARS-CoV-2 Omicron variant emerged, individuals in China had already received an inactivated (INA) or a type 5 adenovirus-vectored (Ad5) SARS-CoV-2 vaccine targeting the wild-type virus. We have recently developed a bivalent recombinant type 5 vaccine targeting both the wild-type strain and the Omicron variant (Ad5-nCoV/O). The objectives of this study were to assess the immunogenicity of the bivalent vaccine as a booster against both the wild type and the Omicron variant. METHODS: In the single immunization model, mice received one intramuscular immunization with monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. In the prime-boost model, mice were primed intramuscularly with an INA or Ad5-vectored vaccine targeting wild-type SARS-CoV-2, and then boosted intramuscularly or intranasally with heterologous or homologous INA or monovalent or bivalent Ad5-vectored vaccines targeting both wild-type SARS-CoV-2 and Omicron variants. The vaccine-induced antibody responses and cellular immune responses were measured using ELISA, pseudovirus-based neutralization assays, the intracellular cytokine staining (ICS) and ELISpot. RESULTS: Single-dose prime vaccination with the monovalent and bivalent vaccines elicited robust antibody responses and CD4 + and CD8 + cellular responses against the spike protein of WT and Omicron SARS-CoV-2. Both intramuscular and intranasal boost vaccination with the bivalent Ad5-nCoV/O following a prime with INA or Ad5-vectored vaccines induced strong serum neutralization antibody responses to both wild type and Omicron variants. A heterologous prime-boost vaccination elicited greater neutralization antibody responses than a homologous prime-boost vaccination when mice were boosted with Ad5-vectored vaccines following a prime with INA. Intranasal boost also resulted in significant mucosal IgA responses. CONCLUSION: The bivalent vaccine Ad5-nCoV/O exhibited robust immunogenicity, inducing broad-spectrum cross-neutralizing antibodies and cellular immune responses against both wild type and Omicron variants of SARS-CoV-2. The results demonstrated the potential of the bivalent vaccine in addressing the challenges posed by emerging SARS-CoV-2 Omicron variants.

The effect of heterogeneous severe drought on all-cause and cardiovascular mortality in the Northern Rockies and Plains of the United States.

Drought is a distinct and complicated climate hazard that regularly leads to severe economic impacts. Changes in the frequency and occurrence of drought due to anthropogenic climate change can lead to new and unanticipated outcomes. To better prepare for health outcomes, more research is needed to develop methodologies to understand potential consequences. This study suggests a new methodology for assessing the impact of monthly severe drought exposure on mortality in the Northern Rockies and Plains of the United States from 2000 to 2018. A two-stage model with the power prior approach was applied to integrate heterogeneous severe drought pattern and estimate overall risk ratios of all-cause and cardiovascular mortality related to multiple drought indices (the US Drought Monitor, 6- and 12-month Standardized Precipitation-Evapotranspiration Index, 6- and 12 month Evaporative Demand Drought Index). Under severe drought, the risk ratios of all-cause mortality are 1.050 (95 % Cr: 1.031 to 1.071, USDM), 1.041 (95 % Cr: 1.022 to 1.060, 6-SPEI), 1.009 (95 % Cr: 0.989 to 1.031, 12SPEI), 1.045 (95 % Cr: 1.022 to 1.067, 6-EDDI), and 1.035 (95 % Cr: 1.009 to 1.062, 12-EDDI); cardiovascular mortality are 1.057 (95 % Cr: 1.023 to 1.091, USDM), 1.028 (95 % Cr: 0.998 to 1.059, 6-SPEI), 1.005 (95 % Cr: 0.973 to 1.040, 12-SPEI), 1.042 (95 % Cr: 1.005 to 1.080, 6-EDDI), and 1.004 (95 % Cr: 0.959 to 1.049, 12-EDDI). Our results showed that (i) a model with properly accounted for heterogeneous exposure pattern had greater risk ratios if statistically significant; (ii) a mid-term (6-month) severe drought had higher risk ratios compared to longer-term (12-month) drought; and (iii) different severe droughts affect populations in a different way. These results expand the existing knowledge of drought relationship to increasing mortality in the United States. The findings from this study highlight the need for communities and policymakers to establish effective drought-prevention initiatives in this region.