Dynamics of measles immunity from birth and following vaccination.

Measles remains a major threat to human health despite widespread vaccination. While we know that maternal antibodies can impair vaccine-induced immunity, the relative contributions of pre-existing immunity levels, maternal and infant characteristics on vaccine responses remain unclear, hampering evidence-based vaccination policy development. Here we combine serological data from 1,505 individuals (aged 0-12 years) in a mother-infant cohort and in a child cohort with empirical models to reconstruct antibody trajectories from birth. We show that while highly heterogeneous across a population, measles antibody evolution is strongly predictive from birth at the individual level, including following vaccination. Further, we find that caesarean section births were linked with 2.56 (95% confidence interval: 1.06-6.37) increased odds of primary vaccine failure, highlighting the long-term immunological consequences of birth route. Finally, we use our new understanding of antibody evolution to critically assess the population-level consequences of different vaccination schedules, the results of which will allow country-level evaluations of vaccine policy.

The IRE1α/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease.

Group 3 innate lymphoid cells (ILC3s) are key players in intestinal homeostasis. Endoplasmic reticulum (ER) stress is linked to inflammatory bowel disease (IBD). Herein, we used cell culture, mouse models, and human specimens to examine if ER stress in ILC3s impacts IBD pathophysiology. We show that mouse intestinal ILC3s exhibited a 24h-rhythmic expression pattern of the master ER stress response regulator, IRE1α/XBP1. Proinflammatory cytokine IL-23 selectively stimulated IRE1α/XBP1 in mouse ILC3s through mitochondrial reactive oxygen species (mtROS). IRE1α/XBP1 was activated in ILC3s of mice exposed to experimental colitis and in inflamed human IBD specimens. Mice with Ire1α deletion in ILC3s (Ire1αΔRorc) showed reduced expression of ER stress response and cytokine genes including Il22 in ILC3s and were highly vulnerable to infections and colitis. Administration of IL-22 counteracted their colitis susceptibility. In human ILC3s, IRE1 inhibitors suppressed cytokine production, which was upregulated by an IRE1 activator. Moreover, the frequencies of intestinal XBP1s+ ILC3s in Crohn's disease patients before administration of ustekinumab, an anti-IL-12/IL-23 antibody, positively correlated with response to treatment. We demonstrate that a non-canonical mtROS-IRE1α/XBP1 pathway augments cytokine production by ILC3s and identify XBP1s+ ILC3s as a potential biomarker for predicting response to anti-IL-23 therapies in IBD.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

An Indoor Fire Detection Method Based on Multi-Sensor Fusion and a Lightweight Convolutional Neural Network.

Indoor fires pose significant threats in terms of casualties and economic losses globally. Thus, it is vital to accurately detect indoor fires at an early stage. To improve the accuracy of indoor fire detection for the resource-constrained embedded platform, an indoor fire detection method based on multi-sensor fusion and a lightweight convolutional neural network (CNN) is proposed. Firstly, the Savitzky-Golay (SG) filter is used to clean the three types of heterogeneous sensor data, then the cleaned sensor data are transformed by means of the Gramian Angular Field (GAF) method into matrices, which are finally integrated into a three-dimensional matrix. This preprocessing stage will preserve temporal dependency and enlarge the characteristics of time-series data. Therefore, we could reduce the number of blocks, channels and layers in the network, leading to a lightweight CNN for indoor fire detection. Furthermore, we use the Fire Dynamic Simulator (FDS) to simulate data for the training stage, enhancing the robustness of the network. The fire detection performance of the proposed method is verified through an experiment. It was found that the proposed method achieved an impressive accuracy of 99.1%, while the number of CNN parameters and the amount of computation is still small, which is more suitable for the resource-constrained embedded platform of an indoor fire detection system.

Loss of Consciousness in a 34 Yo Male Related to Marijuana.

Nontraumatic exertional syncope can be an ominous event reflecting profound arterial hypotension, cerebral hypoperfusion, and transient loss-of consciousness that occurs most commonly in patients with underlying cardiovascular disease. In contradistinction, transient loss-of-consciousness in "healthy adults" is typically vasovagal syncope related to exaggerated orthostatic cardiovascular responses attributed to a hyper-reactive autonomic nervous system. In the present report, a 34 yo male presents to the hospital emergency department (ED) for a sudden loss of consciousness and fall ultimately related to cardiac syncope ascribed to chronic recreational marijuana use complicated by coronary vasospasm.

Cost and health-related quality of life for children hospitalized with respiratory syncytial virus in Central China.

BACKGROUND: The economic burden of respiratory syncytial virus (RSV) infection and its impact on health-related quality of life (HRQoL) are not well-understood in China. This study assessed total cost and HRQoL for children hospitalized with RSV in Central China. METHODS: Based on a prospective case series study in Henan Province in 2020-2021, inpatients aged 0-59 months with RSV-related acute respiratory infections (ARIs) were included into analysis. Total cost included direct medical cost (sum of medical cost before and during hospitalization), direct non-medical cost, and indirect cost. Direct medical cost during hospitalization data were extracted from the hospital information system. Other costs and HRQoL status were obtained from a telephone survey conducted in the caregivers of the enrolled patients. RESULTS: Among 261 RSV-infected inpatients, caregivers of 170 non-severe cases (65.1%, 170/261) were successfully interviewed. Direct medical cost per episode was 1055.3 US dollars (US$) (95% CI: 998.2-1112.5 US$). Direct non-medical cost and indirect cost per episode were 83.6 US$ (95% CI: 77.5-89.7 US$) and 162.4 US$ (95% CI: 127.9-197.0 US$), respectively. Quality adjusted life years (QALY) loss for non-severe RSV hospitalization was 8.9 × 10-3 (95% CI: 7.9 × 10-3 -9.9 × 10-3 ). The majority of inpatients were <1 year of age comprising significantly higher cost and more QALY loss than older children. CONCLUSIONS: RSV-associated hospitalization poses high economic and health burden in Central China particularly for children <1 year old. Our findings are crucial for determining the priority of interventions and allocation of health resources.

GAS5 silencing attenuates hypoxia-induced cardiomyocytes injury by targeting miR-21/PTEN.

INTRODUCTION: Myocardial hypoxia is an important factor causing myocardial infarction (MI). Interestingly, many unknown factors in the molecular mechanism of MI remain unclear. Our study explored the role of lncRNA growth arrest-specific 5 (GAS5) in cell injury under hypoxia. METHODS: AS5 expression was assessed in MI and human cardiomyocytes under hypoxia through RT-qPCR assay. Methyl thiazolyl tetrazolium assay, flow cytometry assay, and transwell assay was carried out for cell viability, cell apoptosis, cell migration, and invasion, respectively. The regulatory target of GAS5 was explored through a dual-luciferase reporter assay. RESULTS: Our findings indicated that the upregulation of GAS5 was related to hypoxia. Downregulation of GAS5 expression could decrease hypoxia-induced cell apoptosis and increase cell migration and invasion. Moreover, GAS 5 targeted miR-21, which regulated the phosphatase and tension homology deleted on chromosome ten gene (PTEN) expression. Furthermore, the knockdown of miR-21 eliminated the effect of GAS5 silencing on cell injury. CONCLUSION: These results indicated that lncRNA GAS5 silencing decreased cardiomyocyte injury by hypoxia-induced through regulating miR-21/PTEN.

Long-term measles antibody profiles following different vaccine schedules in China, a longitudinal study.

Characterizing the long-term kinetics of maternally derived and vaccine-induced measles immunity is critical for informing measles immunization strategies moving forward. Based on two prospective cohorts of children in China, we estimate that maternally derived immunity against measles persists for 2.4 months. Following two-dose series of measles-containing vaccine (MCV) at 8 and 18 months of age, the immune protection against measles is not lifelong, and antibody concentrations are extrapolated to fall below the protective threshold of 200 mIU/ml at 14.3 years. A catch-up MCV dose in addition to the routine doses between 8 months and 5 years reduce the cumulative incidence of seroreversion by 79.3-88.7% by the age of 6 years. Our findings also support a good immune response after the first MCV vaccination at 8 months. These findings, coupled with the effectiveness of a catch-up dose in addition to the routine doses, could be instrumental to relevant stakeholders when planning routine immunization schedules and supplemental immunization activities.

Epidemiological and clinical characteristics of respiratory syncytial virus and influenza infections in hospitalized children before and during the COVID-19 pandemic in Central China.

Background: Globally, the epidemiology of non-SARS-CoV-2 respiratory viruses like respiratory syncytial virus (RSV) and influenza virus was remarkably influenced by the implementation of non-pharmacological interventions (NPIs) during the COVID-19 pandemic. Our study explored the epidemiological and clinical characteristics of pediatric patients hospitalized with RSV or influenza infection before and during the pandemic after relaxation of NPIs in central China. Methods: This hospital-based prospective case-series study screened pediatric inpatients (age ≤ 14 years) enrolled with acute respiratory infections (ARI) for RSV or influenza infection from 2018 to 2021. The changes in positivity rates of viral detection, epidemiological, and clinical characteristics were analyzed and compared. Results: Median ages of all eligible ARI patients from 2018-2019 were younger than those from 2020-2021, so were ages of cases infected with RSV or influenza (RSV: 4.2 months vs. 7.2 months; influenza: 27.3 months vs. 37.0 months). Where the positivity rate for influenza was considerably decreased in 2020-2021 (1.4%, 27/1964) as compared with 2018-2019 (2.9%, 94/3275, P < 0.05), it was increased for RSV (11.4% [372/3275] vs. 13.3% [262/1964], P < 0.05) in the same period. The number of severe cases for both RSV and influenza infection were also decreased in 2020-2021 compared with 2018-2019. Conclusions: The implemented NPIs have had varied impacts on common respiratory viruses. A more effective prevention strategy for RSV infections in childhood is needed.

Fabrication of Densified Rice Husk by Sequential Hot-Compressed Water Treatment, Blending with Poly(vinyl alcohol), and Hot Pressing.

Processing agricultural wastes into densified materials to partially substitute wooden product production is significant for reducing the consumption of forest resources. This work proposes the fabrication of high-strength rice husk (RH)-based composite materials with poly(vinyl alcohol) (PVA) via densification by hot pressing. RH was pretreated in hot-compressed water (HCW) prior to pulverization and blending with PVA or PVA/glycerol (GL). The incorporation of PVA greatly improved the strength, toughness, and waterproofness of the composite plate, which was discussed with the help of a variety of composite characterizations. The tensile strength, flexural strength, and toughness of a composite of HCW-treated RH, PVA, and GL with a mass ratio of 80:20:2 were 42, 81 MPa, and 5.9 MJ/m3, respectively. The HCW treatment and blending with PVA and GL improved those properties of the hot-pressed original RH plate by factors of 2.5, 2.3, and 6.7, respectively, and reduced the water uptake and swelling ratio in water by 57 and 53%, respectively, despite the hydrophilic nature of PVA and GL. Altogether, this work outlines a valuable and sustainable approach to the efficient utilization of agricultural wastes.

Hierarchical hollow-tubular porous carbon microtubes prepared via a mild method for supercapacitor electrode materials with high volumetric capacitance.

In this paper, hollow-tubular porous carbons were synthesized from abundant biomass Cycas fluff (CF) through simple carbonization followed by an NaHCO3 mild activation process. After activation, the tubular structure of the CF was retained, and a hierarchical structure of micropores, mesopores and macropores was formed. When the optimal mass ratio of NaHCO3/CF is 2, the obtained porous carbon CF-HPC-2 sample has a large specific surface area (SSA) of 516.70 m2 g-1 in Brunauer-Emmett-Teller (BET) tests and a total pore volume of 0.33 cm3 g-1. The C, O, N and S contents of CF-HPC-2 were tested as 91.77 at%, 4.09 at%, 3.54 at%, and 0.6 at%, respectively, by elemental analysis. Remarkably, CF-HPC-2 exhibits a high volume capacitance (349.1 F cm-3 at 1 A g-1) as well as a higher rate capability than other biomass carbon materials (289.1 F cm-3 at 10 A g-1). Additionally, the energy density of the CF-HPC-2 based symmetric supercapacitor in 2 M Na2SO4 electrolyte at 20 kW kg-1 is 27.72 W h kg-1. The particular hollow tubular morphology and activated porous structure determine the excellent electrochemical performance of the material. Hence, this synthetic method provides a new way of storing energy for porous carbon as high volumetric capacitance supercapacitor materials.

Inhibition of NOS1 promotes the interferon response of melanoma cells.

BACKGROUND: NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown. METHODS: The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer. RESULTS: NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN[Formula: see text] by upregulation expression of IFN[Formula: see text] simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients. CONCLUSION: These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.

Epstein-Barr Virus Induces Lymphangiogenesis and Lympth Node Metastasis via Upregulation of VEGF-C in Nasopharyngeal Carcinoma.

Lymphatic metastasis is a common clinical symptom in nasopharyngeal carcinoma (NPC), the most common Epstein-Barr virus (EBV)-associated head and neck malignancy. However, the effect of EBV on NPC lymph node (LN) metastasis is still unclear. In this study, we demonstrated that EBV infection is strongly associated with advanced clinical N stage and lymphangiogenesis of NPC. We found that NPC cells infected with EBV promote LN metastasis by inducing cancer-associated lymphangiogenesis, whereas these changes were abolished upon clearance of EBV genomes. Mechanistically, EBV-induced VEGF-C contributed to lymphangiogenesis and LN metastasis, and PHLPP1, a target of miR-BART15, partially contributed to AKT/HIF1a hyperactivity and subsequent VEGF-C transcriptional activation. In addition, administration of anti-VEGF-C antibody or HIF1α inhibitors attenuated the lymphangiogenesis and LN metastasis induced by EBV. Finally, we verified the clinical significance of this prometastatic EBV/VEGF-C axis by determining the expression of PHLPP1, AKT, HIF1a, and VEGF-C in NPC specimens with and without EBV. These results uncover a reasonable mechanism for the EBV-modulated LN metastasis microenvironment in NPC, indicating that EBV is a potential therapeutic target for NPC with lymphatic metastasis. IMPLICATIONS: This research demonstrates that EBV induces lymphangiogenesis in NPC by regulating PHLPP1/p-AKT/HIF1a/VEGF-C, providing a new therapeutic target for NPC with lymphatic metastasis.

The Value of Admission Serological Indicators for Predicting 28-Day Mortality in Intensive Care Patients With Acute Heart Failure: Construction and Validation of a Nomogram.

Background: Acute heart failure (AHF) is a severe clinical syndrome characterized as rapid onset or worsening of symptoms of chronic heart failure (CHF). Risk stratification for patients with AHF in the intensive care unit (ICU) may help clinicians to predict the 28-day mortality risk in this subpopulation and further raise the quality of care. Methods: We retrospectively reviewed and analyzed the demographic characteristics and serological indicators of patients with AHF in the Medical Information Mart for Intensive Care III (MIMIC III) (version 1.4) between June 2001 and October 2012 and our medical center between January 2019 and April 2021. The chi-squared test and the Fisher's exact test were used for comparison of qualitative variables among the AHF death group and non-death group. The clinical variables were selected by using the least absolute shrinkage and selection operator (LASSO) regression. A clinical nomogram for predicting the 28-day mortality was constructed based on the multivariate Cox proportional hazard regression analysis and further validated by the internal and external cohorts. Results: Age > 65 years [hazard ratio (HR) = 2.47], the high Sequential Organ Failure Assessment (SOFA) score (≥3 and ≤8, HR = 2.21; ≥9 and ≤20, HR = 3.29), lactic acid (Lac) (>2 mmol/l, HR = 1.40), bicarbonate ( HCO 3 - ) (>28 mmol/l, HR = 1.59), blood urea nitrogen (BUN) (>21 mg/dl, HR = 1.75), albumin (<3.5 g/dl, HR = 2.02), troponin T (TnT) (>0.04 ng/ml, HR = 4.02), and creatine kinase-MB (CK-MB) (>5 ng/ml, HR = 1.64) were the independent risk factors for predicting 28-day mortality of intensive care patients with AHF (p < 0.05). The novel nomogram was developed and validated with a promising C-index of 0.814 (95% CI: 0.754-0.882), 0.820 (95% CI: 0.721-0.897), and 0.828 (95% CI: 0.743-0.917), respectively. Conclusion: This study provides a new insight in early predicting the risk of 28-day mortality in intensive care patients with AHF. The age, the SOFA score, and serum TnT level are the leading three predictors in evaluating the short-term outcome of intensive care patients with AHF. Based on the nomogram, clinicians could better stratify patients with AHF at high risk and make adequate treatment plans.

Admission Blood Glucose Is Associated With the 30-Days Mortality in Septic Patients: A Retrospective Cohort Study.

Background: Sepsis, as one of the severe diseases, is frequently observed in critically ill patients, especially concurrent with diabetes. Whether admission blood glucose is associated with the prognosis, and outcome of septic patients is still debatable. Methods: We retrospectively reviewed and analyzed the demographic characteristics of septic patients in the Medical Information Mart for Intensive Care III (MIMIC III, version 1.4) between June 2001 and October 2012. The Chi-square and Fisher's exact tests were used for the comparison of qualitative variables among septic patients with different glucose levels and the 30-day mortality in septic patients with diabetes or not. Univariate and stepwise multivariate Cox regression analyses were used to determine the risk factors for 30-day mortality. Kaplan-Meier analysis was conducted to reveal the different 30-day survival probabilities in each subgroup. Results: A total of 2,948 septic patients (910 cases with diabetes, 2,038 cases without diabetes) were ultimately included in the study. The 30-day mortality was 32.4% (956/2,948 cases) in the overall population without any difference among diabetic and non-diabetic septic patients (p = 1.000). Admission blood glucose levels <70 mg/dl were only observed to be significantly associated with the 30-day mortality of septic patients without diabetes (hazard ratio (HR) = 2.48, p < 0.001). After adjusting for confounders, age >65 years (HR = 1.53, p = 0.001), the Sequential Organ Failure Assessment (SOFA) score >5 (HR = 2.26, p < 0.001), lactic acid >2 mmol/L (Lac, HR = 1.35, p = 0.024), and platelet abnormality (<100 k/ul: HR = 1.49; >300 k/ul: HR = 1.36, p < 0.001) were the independent risk factors for 30-day mortality in septic patients with diabetes. In non-diabetes population, age >65 years (HR = 1.53, p < 0.001), non-White or non-Black patients (HR = 1.30, p = 0.004), SOFA score >5 (HR = 1.56, p < 0.001), blood glucose <70 mg/dl (HR = 1.91, p = 0.003), anion gap (AG) >2 mmol/L (HR = 1.60, p < 0.001), Lac (HR = 1.61, p < 0.001), urea nitrogen >21 mg/dl (HR = 1.45, p = 0.001), alanine aminotransferase (ALT, HR = 1.31, p = 0.009), total bilirubin >1.2 mg/dl (HR = 1.20, p = 0.033), and low hemoglobin (HR = 1.34, p = 0.001) were the independent risk factors for 30-day mortality. Conclusions: Our results indicate admission blood glucose, especially in terms of <70 mg/dl, is the key signaling in predicting the worse 30-day survival probability of septic patients without diabetes, which could help clinicians to make a more suitable and precise treatment modality in dealing with septic patients.

Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease.

In the present study, mitral valve tissues from three mitral stenosis patients with RHD by valve replacement and two healthy donors were harvested and conducted DNA methylation signature on PRKCA by MeDIP-qPCR. The presence of hypomethylated CpG islands at promoter and 5' terminal of PRKCA was observed in RHD accompanied with highly expressed PRKCA and down-regulated antisense long non-coding RNA (lncRNA) PRKCA-AS1 compared to health control. Furthermore, the enrichments of DNMT1/3A/3B on PRKCA were detected by ChIP-qPCR assay in vivo and in human cardiomyocyte AC16 and RL-14 cells exposed to TNF-α in vitro, and both demonstrated that DNMT1 substantially contributed to DNA methylation. Additionally, PRKCA-AS1 was further determined to bind with promoter of PRKCA via 5' terminal and interact with DNMT1 via 3' terminal. Taken together, our results illuminated a novel regulatory mechanism of DNA methylation on regulating PRKCA transcription through lncRNA PRKCA-AS1, and shed light on the molecular pathogenesis of RHD occurrence.

The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells.

One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.