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Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation. Parasitism is a widespread evolutionary strategy. A study that spans functional and evolutionary genomics identifies the molecular basis and history underlying two genes that have mediated divergent parasitic strategies (specialist vs generalist) between two sister species of parasitoid wasp.

Objectives The triglyceride-glucose index (TyG) is an emerging marker of metabolic health, yet its association with mortality across different glucose metabolism statuses remains unclear. This study aimed to investigate the relationship between the TyG and the risk of all-cause and cardiovascular mortality among individuals with normoglycemia, dysglycemia, and diabetes mellitus. Methods Participants from nine cycles of the National Health and Nutrition Examination Survey (NHANES) were included and categorized into three groups: normoglycemia, dysglycemia, and diabetes. Cox regression and restricted cubic spline (RCS) analyses were performed to evaluate the linear and nonlinear associations between TyG and mortality. To assess the predictive power of TyG and the atherogenic index of plasma (AIP) for mortality, time-dependent receiver operating characteristic (ROC) curves were constructed. Subgroup analyses were conducted based on age, sex, and blood pressure status. Results During a median follow-up of 9.2 years, a total of 2199 all-cause deaths and 606 cardiovascular deaths were documented. In the normoglycemic group, a single standard unit increase in TyG was associated with a 35% higher risk of all-cause mortality and a 38% higher risk of cardiovascular mortality (HR: 1.35, 95% CI 1.17–1.56; HR: 1.38, 95% CI 1.04–1.84, respectively). Among participants with diabetes, RCS analysis revealed a U-shaped association between TyG and all-cause/cardiovascular mortality, with an inflection point at 9.1. No significant associations were observed in the dysglycemia group. TyG demonstrated superior predictive performance compared to the AIP for 3-year mortality in both normoglycemic and diabetic individuals. Subgroup analyses identified significant interaction effects of age and sex on the association between TyG and mortality. Conclusion TyG was associated with an increased risk of all-cause and cardiovascular death in the normoglycemic subgroup, but not in the dysglycemic subgroup. In the diabetes subgroup, the association between the TyG and mortality was nonlinear. The predictive value of TyG across different glucose metabolism statuses provides new evidence for medical practice. Graphical abstract A total of 23,103 participants with normoglycemia (n=10,078), dysglycemia (n=8748), and diabetes (n=4277) were included. The median follow-up time was 9.2 years. Weighted COX regression results (upper), restricted cubic spline results (lower left), and time-dependent (cut-off value of 36 months) receiver operating characteristic curve results (lower right).TyG, triglyceride glucose index; AIP, atherogenic index of plasma; RCS, restricted cubic spline; ROC, receiver operating characteristic. *The results of the Cox regression used TyG as a continuous variable.

Background In this study, we aimed to perform a comprehensive analysis on the metagenomic next-generation sequencing for the etiological diagnosis of septic patients, and further to establish optimal read values for detecting common pathogens. Methods In this single-center retrospective study, septic patients who underwent pathogen detection by both microbial culture and metagenomic next-generation sequencing in the intensive care unit of the Second People’s Hospital of Shenzhen from June 24, 2015, to October 20, 2019, were included. Results A total of 193 patients with 305 detected specimens were included in the final analysis. The results of metagenomic next-generation sequencing showed significantly higher positive rates in samples from disparate loci, including blood, bronchoalveolar lavage fluid, and cerebrospinal fluid, as well as in the determination of various pathogens. The optimal diagnostic reads were 2893, 1825.5, and 892.5 for Acinetobacter baumannii, Pseudomonas aeruginosa , and Klebsiella pneumoniae , respectively. Conclusions The metagenomic next-generation sequencing is capable of identifying multiple pathogens in specimens from septic patients, and shows significantly higher positive rates than culture-based diagnostics. The optimal diagnostic reads for frequently detected microbes might be useful for the clinical application of metagenomic next-generation sequencing in terms of timely and accurately determining etiological pathogens for suspected and confirmed cases of sepsis due to well-performed data interpretation.

Background In 2017, WHO published a list of bacteria for which new antibiotics are urgently needed. The main bacteria are common causes of nosocomial meningitis. The key focuses are carbapenem resistance, vancomycin resistance, methicillin resistance, and extended-spectrum beta-lactamase (ESBL) production. There are a limited number of appropriate drugs to treat nosocomial meningitis due to resistance and permeability of drugs, we aimed to discuss the urgency by analyzing the causes and related outcomes of antimicrobial resistance in the pathogens. Methods We collected 333 patients in whom 854 pathogens were isolated. Poor outcome was defined as a Glasgow Outcome Scale of 1–3. The adjusted analysis of risk factors for poor outcomes was performed using a generalized linear model. Results The main pathogens were Enterobacteriaceae ( n  = 186, 21.8%), A. baumannii ( n  = 66, 7.7%), S. aureus ( n  = 38, 4.4%), E. faecium ( n  = 27, 3.2%), and P. aeruginosa ( n  = 16, 1.9%). Vancomycin resistance was found in 0% (0/38) of S. aureus and 22.2% (6/27) of E. faecium . Carbapenem resistance was found in 35.5% (16/186) of Enterobacteriaceae , 80.3% (53/66) of A. baumannii and 37.5% (6/16) of P. aeruginosa . ESBL production occurred in 54.8% (102/186) of Enterobacteriaceae and methicillin resistance occurred in 39.5% (15/38) of S. aureus . Additionally, 136 (40.8%) cases had poor outcomes. Vancomycin or carbapenem resistance (relative risk 1.98, 95% confidence interval [1.72–4.12], p  < 0.001) and ESBL production or methicillin resistance (relative risk 1.60, 95% confidence interval [1.10–3.07], p  = 0.020) were risk factors for poor outcomes. Conclusion In nosocomial meningitis, drug-resistant A. baumannii and Enterobacteriaceae were predominant, requiring urgent development of new antimicrobials for treatment. Clinical trial Not applicable.

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite’s manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system. Evolutionary arms races can drive adaptations in hosts and parasites as well as among competing parasites. A combination of multi-omics and functional tests identifies a set of genes that allow a parasitic wasp to minimize intraspecific competition by inducing hosts to escape before more wasps can parasitize them.

Summary Healthcare-associated ventriculitis and meningitis (HCAVM) is a severe infection and is associated with high morbidity, mortality, and poor functional prognosis, and the associated microorganisms can be skin flora or nosocomial pathogens, most commonly Gram-negative bacteria. Enterococci -related HCAVM have rarely been discussed systemically, the related drug resistance and outcomes have been poorly researched. In this multicenter retrospective case series, we analyzed patients with Enterococci -related HCAVM from three tertiary hospitals. Our study assessed bacterial resistance patterns, antimicrobial treatment strategies, and clinical outcomes in this patient cohort. A total of 94 strains of Enterococci causing HCAVM were identified, including 58 strains of Enterococcus faecalis and 34 strains of Enterococcus faecium . Vancomycin resistance rate was 7.4%(7/94), which only occurred in E. faecium . The linezolid resistance rate was 1.1%(1/94). Ten tested antimicrobial agents showed higher resistance rates against E. faecium than against E. faecalis . Vancomycin was used in 88 patients as empirical treatment, which was changed to linezolid in 12 patients, including those with vancomycin-resistant E. faecium . Four (4.3%) patients experienced ineffective treatments, eight (8.5%) had poor outcomes, and the treatment course was 15.3 ± 10.9 days. In conclusion, our findings reveal the different resistance rates of Enterococcus faecalis and Enterococcus faecium to vancomycin and linezolid, reveal the clinical epidemiological characteristics of Enterococci -related HCAVM, and provide an important reference for the selection of antimicrobial agents.

The success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid, Trichopria drosophilae , which parasitizes a broad range of Drosophila hosts, including the globally invasive species D. suzukii . We found that T. drosophilae had developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell—teratocytes—that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.

Trichogramma dendrolimi is an essential egg parasitic wasp with a broad host range and has been widely used for controlling agricultural and forestry pests. Despite the availability of fragmented genomes of Trichogramma , a high-quality, chromosome-level genome reference is not yet available for this diverse genus. In this study, we assembled a high-quality chromosome-level genome of T. dendrolimi using PacBio CLR long sequencing and further scaffolded it with Hi-C technologies. The genome size was 216.24 Mb, featuring a N50 of 39.07 Mb, and 98.79% of scaffolds were anchored to five chromosomes. In addition, we annotated 12,902 protein-coding genes and 60.74 Mb repeat sequences for this genome assembly. In conclusion, our chromosome-level genome assembly provided important genomic resources that benefit the utilization of Trichogramma parasitoids in pest control.

Background. Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. Methods. Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged > 65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). Results. The overall prevalence of HI titers of ≥40 against A(H3N2) v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. Conclusions. A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread.

ABSTRACT Background Recent research highlights the immune system's role in AD pathogenesis and promising prospects of natural compounds in treatment. This study explores immunity‐related biomarkers and potential natural products using bioinformatics, machine learning, molecular docking, and kinetic simulation. Methods Differentially expressed genes (DEGs) in AD were analyzed using GSE5281 and GSE132903 datasets. Important AD module genes were identified using a weighted co‐expression algorithm (WGCNA), and immune‐related genes (IRGs) were obtained from the ImmPortPortal database. Intersecting these genes yielded important IRGs. Then, the least absolute shrinkage and selection operator (LASSO) and other methods screened common immune‐related AD markers. Biological pathways were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The accuracy of these markers was assessed by subject operator signature (ROC) curves and validated in the GSE122063 dataset. The datasets was then subjected to immunoinfiltration analysis. Multiple compound databases were used to analyze core Chinese medicines and components. Molecular docking and kinetic simulation verification were used for further verification. Results A total of 1360 differential genes and 5 biomarkers (PGF, GFAP, GPI, SST, NFKBIA) were identified, showing excellent diagnostic efficiency. GSEA revealed markers associated with Oxidative phosphorylation, Nicotine addiction, and Hippo signaling pathway. Immune infiltration analysis showed dysregulation in multiple immune cell types in AD brains, with significant interactions between markers and 5 immune cell types. A total of 27 possible herbs and 7 core compounds were eventually identified. The binding environment of GPI‐luteolin and GPI‐stigasterol was relatively stable and showed good affinity. Conclusions PGF, GFAP, SST, GPI, and NFKBIA were identified for early AD diagnosis, associated with immune cells and pathways in AD brains. 7 promising natural compounds, including luteolin and stigmasterol, were screened for targeting these biomarkers. We used a variety of methods to identify biomarkers and compounds of Alzheimer's disease, providing new insights into the clinical research transformation of Alzheimer's disease.