Integrated serum proteomic and N-glycoproteomic characterization of dengue patients.

Dengue fever is a mosquito-borne viral disease caused by the dengue virus (DENV). It poses a public health threat globally and, while most people with dengue have mild symptoms or are asymptomatic, approximately 5% of affected individuals develop severe disease and need hospital care. However, knowledge of the molecular mechanisms underlying dengue infection and the interaction between the virus and its host remains limited. In the present study, we performed a quantitative proteomic and N-glycoproteomic analysis of serum from 19 patients with dengue and 11 healthy people. The results revealed distinct proteomic and N-glycoproteomic landscapes between the two groups. Notably, we report for the first time the changes in the serum N glycosylation pattern following dengue infection and provide abundant information on glycoproteins, glycosylation sites, and intact N-glycopeptides using recently developed site-specific glycoproteomic approaches. Furthermore, a series of key functional pathways in proteomic and N-glycoproteomic were identified. Collectively, our findings significantly improve understanding of host and DENV interactions and the general pathogenesis and pathology of DENV, laying a foundation for functional studies of glycosylation and glycan structures in dengue infection.

Multiple factors trigger the formation and resuscitation of the VBNC state in alcohol-producing Klebsiella pneumoniae.

Klebsiella pneumoniae can enter a viable but nonculturable (VBNC) state to survive in unfavorable environments. Our research found that high-, medium-, and low-alcohol-producing K. pneumoniae strains are associated with nonalcoholic fatty liver disease. However, the presence of the three Kpn strains has not been reported in the VBNC state or during resuscitation. In this study, the effects of different strains, salt concentrations, oxygen concentrations, temperatures, and nutrients in K. pneumoniae VBNC state were evaluated. The results showed that high-alcohol-producing K. pneumoniae induced a slower VBNC state than medium-alcohol-producing K. pneumoniae, and low-alcohol-producing K. pneumoniae. A high-salt concentration and micro-oxygen environment accelerated the loss of culturability. Simultaneously, both real-time quantitative PCR and droplet digital PCR were developed to compare the quantitative comparison of three Kpn strain VBNC states by counting single-copy gene numbers. At 22°C or 37°C, the number of culturable cells decreased significantly from about 108 to 105-106 CFU/mL. In addition, imipenem, ciprofloxacin, polymyxin, and phiW14 inhibited cell resuscitation but could not kill VBNC-state cells. These results revealed that the different environments evaluated play different roles in the VBNC induction process, and new effective strategies for eliminating VBNC-state cells need to be further studied. These findings provide a better understanding of VBNC-state occurrence, maintenance, detection, and absolute quantification, as well as metabolic studies of resuscitation resistance and ethanol production.IMPORTANCEBacteria may enter VBNC state under different harsh environments. Pathogenic VBNC bacteria cells in clinical and environmental samples pose a potential threat to public health because cells cannot be found by routine culture. The alcohol-producing Kpn VBNC state was not reported, and the influencing factors were unknown. The formation and recovery of VBNC state is a complete bacterial escape process. We evaluated the influence of multiple induction conditions on the formation of VBNC state and recovery from antibiotic and bacteriophage inhibition, and established a sensitive molecular method to enumerate the VBNC cells single-copy gene. The method can improve the sensitivity of pathogen detection in clinical, food, and environmental contamination monitoring, and outbreak warning. The study of the formation and recovery of VBNC-state cells under different stress environments will also promote the microbiological research on the development, adaptation, and resuscitation in VBNC-state ecology.

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been reported as a novel predictor for atherosclerosis and cardiovascular outcomes. This study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion (CTO) patients. METHODS: A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up period. Patients were divided into tertiles according to their baseline NLR levels at admission: low (n = 223), intermediate (n = 223), and high (n = 224). The incidence of major adverse cardiac events (MACEs) during the follow-up period, including all-cause death, nonfatal myocardial infarction (MI), or ischemia-driven revascularization, were compared among the three groups. RESULTS: Major adverse cardiac events were observed in 27 patients (12.1%) in the low tertile, 40 (17.9%) in the intermediate tertile, and 61 (27.2%) in the high NLR tertile (P < 0.001). Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE, ischemia-driven coronary revascularization, non-fatal MI, and mortality in patients within the high tertile than those in the low and intermediate groups (all P < 0.001). Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE (hazard ratio [HR] = 2.21; 95% confidence interval [CI]: 1.21-4.03; P = 0.009), ischemia-driven coronary revascularization (HR = 3.19; 95% CI: 1.56-6.52; P = 0.001), MI (HR = 2.61; 95% CI: 1.35-5.03; P = 0.043) and mortality (HR = 3.78; 95% CI: 1.65-8.77; P = 0.001). CONCLUSION: Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently predict cardiovascular risk in patients with CTO.

Clinical features and viral load variations of Mpox: a retrospective study in Chongqing, China.

PURPOSE: Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. METHOD: We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. RESULTS: As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. CONCLUSION: In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Identification and Characterization of Three Novel Solemo-like Viruses in the White-Backed Planthopper, Sogatella furcifera.

Agricultural insects play a crucial role in transmitting plant viruses and host a considerable number of insect-specific viruses (ISVs). Among these insects, the white-backed planthoppers (WBPH; Sogatella furcifera, Hemiptera: Delphacidae) are noteworthy rice pests and are responsible for disseminating the southern rice black-streaked dwarf virus (SRBSDV), a significant rice virus. In this study, we analyzed WBPH transcriptome data from public sources and identified three novel viruses. These newly discovered viruses belong to the plant-associated viral family Solemoviridae and were tentatively named Sogatella furcifera solemo-like virus 1-3 (SFSolV1-3). Among them, SFSolV1 exhibited a prevalent existence in different laboratory populations, and its complete genome sequence was obtained using rapid amplification of cDNA ends (RACE) approaches. To investigate the antiviral RNA interference (RNAi) response in WBPH, we conducted an analysis of virus-derived small interfering RNAs (vsiRNAs). The vsiRNAs of SFSolV1 and -2 exhibited typical patterns associated with the host's siRNA-mediated antiviral immunity, with a preference for 21- and 22-nt vsiRNAs derived equally from both the sense and antisense genomic strands. Furthermore, we examined SFSolV1 infection and distribution in WBPH, revealing a significantly higher viral load of SFSolV1 in nymphs' hemolymph compared to other tissues. Additionally, in adult insects, SFSolV1 exhibited higher abundance in male adults than in female adults.

A pyruvate transporter in the apicoplast of apicomplexan parasites.

Pyruvate lies at a pivotal node of carbon metabolism in eukaryotes. It is involved in diverse metabolic pathways in multiple organelles, and its interorganelle shuttling is crucial for cell fitness. Many apicomplexan parasites harbor a unique organelle called the apicoplast that houses metabolic pathways like fatty acid and isoprenoid precursor biosyntheses, requiring pyruvate as a substrate. However, how pyruvate is supplied in the apicoplast remains enigmatic. Here, deploying the zoonotic parasite Toxoplasma gondii as a model apicomplexan, we identified two proteins residing in the apicoplast membranes that together constitute a functional apicoplast pyruvate carrier (APC) to mediate the import of cytosolic pyruvate. Depletion of APC results in reduced activities of metabolic pathways in the apicoplast and impaired integrity of this organelle, leading to parasite growth arrest. APC is a pyruvate transporter in diverse apicomplexan parasites, suggesting a common strategy for pyruvate acquisition by the apicoplast in these clinically relevant intracellular pathogens.

Unveiling shared biomarkers and therapeutic targets between systemic lupus erythematosus and heart failure through bioinformatics analysis.

Background: Systemic lupus erythematosus (SLE) is frequently accompanied by various complications, with cardiovascular diseases being particularly concerning due to their high mortality rate. Although there is clinical evidence suggesting a potential correlation between SLE and heart failure (HF), the underlying shared mechanism is not fully understood. Therefore, it is imperative to explore the potential mechanisms and shared therapeutic targets between SLE and HF. Methods: The SLE and HF datasets were downloaded from the NCBI Gene Expression Omnibus database. Differentially expressed genes (DEGs) in both SLE and HF were performed using "limma" R package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) analyses were conducted to analyze the enriched functions and pathways of DEGs in both SLE and HF datasets. Protein-Protein Interaction network (PPI) and the molecular complex detection (MCODE) plugins in the Cytoscape software were performed to identify the shared hub genes between SLE and HF datasets. R package "limma" was utilized to validate the expression of hub genes based on SLE (GSE122459) and HF (GSE196656) datasets. CIBERSORT algorithm was utilized to analyze the immune cell infiltration of SLE and HF samples based on SLE (GSE112087) and HF (GSE116250) datasets. A weighted gene co-expression network analysis (WGCNA) network was established to further validate the hub genes based on HF dataset (GSE116250). Molecular biology techniques were conducted to validate the hub genes. Results: 999 shared DGEs were identified between SLE and HF datasets, which were mainly enriched in pathways related to Th17 cell differentiation. 5 shared hub genes among the common DGEs between SLE and HF datasets were screened and validated, including HSP90AB1, NEDD8, RPLP0, UBB, and UBC. Additionally, 5 hub genes were identified in the central part of the MEbrown module, showing the strongest correlation with dilated cardiomyopathy. HSP90AB1 and UBC were upregulated in failing hearts compared to non-failing hearts, while UBB, NEDD8, and RPLP0 did not show significant changes. Conclusion: HSP90AB1 and UBC are closely related to the co-pathogenesis of SLE and HF mediated by immune cell infiltration. They serve as promising molecular markers and potential therapeutic targets for the treatment of SLE combined with HF.

Inhibition of the ATP synthase increases sensitivity of Escherichia coli carrying mcr-1 to polymyxin B.

Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli. Here we investigated several ATP synthase inhibitors, N,N'-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1-positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na2ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.

The placental blood perfusion and LINC00473-mediated promotion of trophoblast apoptosis in fetal growth restriction.

This study aimed to investigate placental microblood flow perfusion in fetal growth restriction (FGR) both pre- and post-delivery, and explore the influence of LINC00473 and its downstream targets on FGR progression in trophoblast cells. Placental vascular distribution, placental vascular index (VIMV), CD34 expression, and histological changes were compared between control and FGR groups. FGR-related differentially expressed genes (DEGs) were analyzed and validated by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in placentae. In vitro experiments examined the regulatory relationships among LINC00473, miR-5189-5p, and StAR, followed by investigations into their impacts on cell proliferation and apoptosis. FGR placentae exhibited irregular shapes, uneven parenchymal echo, stromal dysplasia, ischemic infarction, and variable degrees of thickening in some cases. FGR samples showed less prominent mother vessel lakes, significantly lower VIMV, and decreased CD34 expression. Hematoxylin & eosin (H&E) staining revealed placental fibrosis, fibrin adhesion, infarction, and interstitial dysplasia in FGR. LINC00473, miR-5189-5p, and StAR were identified as DEG, with qPCR demonstrating a significant increase in LINC00473 and a decrease in miR-5189-5p in FGR, while both qPCR and IHC indicated a significant increase in StAR expression. LINC00473 served as an endogenous sponge against miR-5189-5p in human HTR-8/SV neo cells, and StAR expression was regulated by both LINC00473 and miR-5189-5p. Dysregulation of these genes affected cell proliferation and apoptosis. Pathological changes in the placenta are significant contributors to FGR, with placental microblood flow potentially serving as an indicator for monitoring its progression. LINC00473 and its downstream targets may modulate trophoblasts proliferation and apoptosis, thus influencing the onset of FGR, suggesting novel avenues for diagnosis and treatment.

Prediabetes and diabetes were attributed to the prevalence and severity of sarcopenia in middle-aged and elderly adults.

BACKGROUND: Sarcopenia and diabetes are both prevalent health problems worldwide. However, little is known about the relationship between prediabetes and the prevalence and severity of sarcopenia. Therefore, the current study aimed to explore the association between glucose status and the components of sarcopenia, including low muscle mass (LMM), low muscle strength (LMS) and low gait speed (LGS) in US adults. METHODS: Data from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES) were analyzed. A total of 4002 participants aged ≥ 50 years with available information on glucose status (NGR: 1939 cases; prediabetes: 1172 cases; diabetes: 891 cases) and sarcopenia were included in this study. Sarcopenia was defined according to the Foundation for National Institute of Health criteria. Muscle mass, muscle strength and gait speed were used to evaluate sarcopenia and its severity. Weighed multivariable logistic regression were used to explore the association between glucose status and the components of sarcopenia. The hypothetical population attributable fraction (PAF) for the glucose status was also calculated. RESULTS: The mean age of the cohort was 63.01 ± 9.89 years, with 49.4% being male. Multiple logistic regression analysis suggested that diabetes was an independent risk factor for sarcopenia (OR = 5.470, 95% CI 1.551-19.296) and showed a marginal association with severe sarcopenia (OR = 10.693, 95% CI 0.955-119.73) compared to NGR in men, but not in women. Additionally, prediabetes was independently associated with severe sarcopenia (OR = 3.647, 95% CI 1.532-8.697), LMS (OR = 1.472, 95% CI 1.018-2.127) and LGS (OR = 1.673, 95% CI 1.054-2.655) in the entire cohort. When stratifying by gender, we further observed that prediabetes was significantly associated with LMS in men (OR = 1.897, 95% CI 1.019-3.543) and related to LMM (OR = 3.174, 95% CI 1.287-7.829) and LGS (OR = 2.075, 95% CI 1.155-3.727) in women. HbA1c was positively associated with the prevalence of sarcopenia in men (OR = 1.993, 95% CI 1.511-2.629). PAF showed that diabetes accounted for 16.3% of observed sarcopenia cases. Maintaining NGR in the entire population could have prevented 38.5% of sarcopenia cases and 50.9% of severe sarcopenia cases. CONCLUSIONS: Prediabetes and diabetes were independently associated with the prevalence and severity of sarcopenia in US population. Slowing down the progression of hyperglycemia could have prevented a significant proportion of sarcopenia cases.

Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). Methods: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. Results: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Conclusion: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

An axonemal intron splicing program sustains Plasmodium male development.

Differentiation of male gametocytes into flagellated fertile male gametes relies on the assembly of axoneme, a major component of male development for mosquito transmission of the malaria parasite. RNA-binding protein (RBP)-mediated post-transcriptional regulation of mRNA plays important roles in eukaryotic sexual development, including the development of female Plasmodium. However, the role of RBP in defining the Plasmodium male transcriptome and its function in male gametogenesis remains incompletely understood. Here, we performed genome-wide screening for gender-specific RBPs and identified an undescribed male-specific RBP gene Rbpm1 in the Plasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with the spliceosome E complex and regulates the splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal protein expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. The splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcriptional regulation essential for Plasmodium male development.

Insufficient KIF15 during porcine oocyte ageing induces HDAC6-based microtubule instability.

During aging, oocytes display cytoskeleton dynamics defects and aneuploidy, leading to embryonic aneuploidy, which in turn causes miscarriages, implantation failures, and birth defects. KIF15 (also known as Hklp2), a member of the kinesin-12 superfamily, is a cytoplasmic motor protein reported to be involved in Golgi and vesicle-related transport during mitosis in somatic cells. However, the regulatory mechanisms of KIF15 during meiosis in porcine oocytes and the connection with postovulatory aging remain unclear. In present study, we found that KIF15 is expressed during porcine oocyte maturation, and its localization is dependent on microtubule dynamics. Furthermore, the level of KIF15 expression decreased in postovulatory aged oocytes. The decrease in KIF15 blocked polar body extrusion, thereby hindering oocyte maturation. We demonstrated that KIF15 defects contributed to abnormal spindle morphologies and chromosome misalignment, possibly due to microtubule instability, as evidenced by microtubule depolymerization after cold treatment. Additionally, our data indicated that KIF15 modulates HDAC6 to affect tubulin acetylation in oocytes. Taken together, these results suggest that KIF15 regulates HDAC6-related microtubule stability for spindle organization in porcine oocytes during meiosis, which may contribute to the decline in maturation competence in aged porcine oocytes.

Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Improving associative memory in younger and older adults with unitization: evidence from meta-analysis and behavioral studies.

Introduction: The finding that familiarity can support associative memory by unitizing the to -be-learned items into a novel representation has been widely accepted, but its effects on overall performance of associative memory and recollection are still controversial. Methods: The current study aims to elucidate these discrepancies by identifying potential moderating factors through a combined approach of meta-analysis and behavioral experiment. Results: Results consistently showed that changes in the level of unitization and age groups were two important moderators. Specifically, unitization enhanced younger and older adults' associative memory and its supporting processes (i.e., familiarity and recollection) when the level of unitization between studied and rearranged pairs was changed. However, when this level remained constant, unitization exhibited no impact on associative memory and familiarity in younger adults, but showed an enhanced effect in older adults. Furthermore, results revealed a marked group difference between younger and older adults in associative memory when the unitization level of noncompound words remained unaltered. Upon breaking this condition, the group difference was reduced by enhancing familiarity or recollection. Discussion: These findings not only clarify some of the inconsistencies in the literature concerning the impact of unitization on associative memory, but also suggest that unitization is a beneficial strategy for reducing group difference in associative memory, with its effectiveness varying according to the level of unitization changes.

Histone methyltransferase MLL4 protects against pressure overload-induced heart failure via a THBS4-mediated protection in ER stress.

Pressure overload-induced pathological cardiac hypertrophy eventually leads to heart failure (HF). Unfortunately, lack of effective targeted therapies for HF remains a challenge in clinical management. Mixed-lineage leukemia 4 (MLL4) is a member of the SET family of histone methyltransferase enzymes, which possesses histone H3 lysine 4 (H3K4)-specific methyltransferase activity. However, whether and how MLL4 regulates cardiac function is not reported in adult HF. Here we report that MLL4 is required for endoplasmic reticulum (ER) stress homeostasis of cardiomyocytes and protective against pressure overload-induced cardiac hypertrophy and HF. We observed that MLL4 is increased in the heart tissue of HF mouse model and HF patients. The cardiomyocyte-specific deletion of Mll4 (Mll4-cKO) in mice leads to aggravated ER stress and cardiac dysfunction following pressure overloading. MLL4 knockdown neonatal rat cardiomyocytes (NRCMs) also display accelerated decompensated ER stress and hypertrophy induced by phenylephrine (PE). The combined analysis of Cleavage Under Targets and Tagmentation sequencing (CUT&Tag-seq) and RNA sequencing (RNA-seq) data reveals that, silencing of Mll4 alters the chromatin landscape for H3K4me1 modification and gene expression patterns in NRCMs. Interestingly, the deficiency of MLL4 results in a marked reduction of H3K4me1 and H3K27ac occupations on Thrombospondin-4 (Thbs4) gene loci, as well as Thbs4 gene expression. Mechanistically, MLL4 acts as a transcriptional activator of Thbs4 through mono-methylation of H3K4 and further regulates THBS4-dependent ER stress response, ultimately plays a role in HF. Our study indicates that pharmacologically targeting MLL4 and ER stress might be a valid therapeutic approach to protect against cardiac hypertrophy and HF.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

The dynamic molecular characteristics of neutrophils are associated with disease progression in dengue patients.

Dengue, the most prevalent mosquito-borne disease worldwide, poses a significant health burden. This study integrates clinical data and transcriptomic datasets from different phases of dengue to investigate distinctive and shared cellular and molecular features. Clinical data from 29 dengue patients were collected and analyzed alongside a public transcriptomic data set (GSE28405) to perform differential gene expression analysis, functional enrichment, immune landscape assessment, and development of machine learning model. Neutropenia was observed in 54.79% of dengue patients, particularly during the defervescence phase (65.79%) in clinical cohorts. Bioinformatics analyses corroborated a significant reduction in neutrophil immune infiltration in dengue patients. Receiver operating characteristic curve analysis demonstrated that dynamic changes in neutrophil infiltration levels could predict disease progression, especially during the defervescence phase, with the area under the curve of 0.96. Three neutrophil-associated biomarkers-DHRS12, Transforming growth factor alpha, and ZDHHC19-were identified as promising for diagnosing and predicting dengue progression. In addition, the activation of neutrophil extracellular traps was significantly enhanced and linked to FcγR-mediated signaling pathways and Toll-like receptor signaling pathways. Neutrophil activation and depletion play a critical role in dengue's immune response. The identified biomarkers and their associated pathways offer potential for improved diagnosis and understanding of dengue pathogenesis and progression.