miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke.

Promotion of new blood vessel formation is a new strategy for treating ischemic stroke. Non-coding miRNAs have been recently considered potential therapeutic targets for ischemic stroke. miR-181b has been shown to promote angiogenesis in hypoxia and traumatic brain injury model, while its effect on ischemic stroke remains elusive. In this study, we found that overexpression of miR-181b in brain microvascular endothelial cells subjected to oxygen-glucose deprivation in vitro restored cell proliferation and enhanced angiogenesis. In rat models of focal cerebral ischemia, overexpression of miR-181b reduced infarction volume, promoted angiogenesis in ischemic penumbra, and improved neurological function. We further investigated the molecular mechanism by which miR-181b participates in angiogenesis after ischemic stroke and found that miR-181b directly bound to the 3'-UTR of phosphatase and tensin homolog (PTEN) mRNA to induce PTEN downregulation, leading to activation of the protein kinase B (Akt) pathway, upregulated expression of vascular endothelial growth factors, down-regulated expression of endostatin, and promoted angiogenesis. Taken together, these results indicate that exogenous miR-181b exhibits neuroprotective effects on ischemic stroke through activating the PTEN/Akt signal pathway and promoting angiogenesis.

Cross-species infection potential of avian influenza H13 viruses isolated from wild aquatic birds to poultry and mammals.

Wild aquatic birds are the primary hosts of H13 avian influenza viruses (AIVs). Herein, we performed a genetic analysis of two H13 AIVs isolated from wild birds in China and evaluated their infection potential in poultry to further explore the potential for transmission from wild aquatic birds to poultry. Our results showed that the two strains belong to different groups, one strain (A/mallard/Dalian/DZ-137/2013; abbreviated as DZ137) belongs to Group I, whereas the other strain (A/Eurasian Curlew/Liaoning/ZH-385/2014; abbreviated as ZH385) belongs to Group III. In vitro experiments showed that both DZ137 and ZH385 can replicate efficiently in chicken embryo fibroblast cells. We found that these H13 AIVs can also efficiently replicate in mammalian cell lines, including human embryonic kidney cells and Madin-Darby canine kidney cells. In vivo experiments showed that DZ137 and ZH385 can infect 1-day-old specific pathogen-free (SPF) chickens, and that ZH385 has a higher replication ability in chickens than DZ137. Notably, only ZH385 can replicate efficiently in 10-day-old SPF chickens. However, neither DZ137 nor ZH385 can replicate well in turkeys and quails. Both DZ137 and ZH385 can replicate in 3-week-old mice. Serological surveillance of poultry showed a 4.6%-10.4% (15/328-34/328) antibody-positive rate against H13 AIVs in farm chickens. Our findings indicate that H13 AIVs have the replication ability in chickens and mice and may have a risk of crossing the host barrier from wild aquatic birds to poultry or mammals in the future.

A differentiation roadmap of murine placentation at single-cell resolution.

The placenta is one of the most important yet least understood organs. Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5-E14.5) at one-day intervals. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. An updated differentiation roadmap of mouse trophoblast lineages is presented following systematic transcriptome analyses. Based on transcriptomic regulatory network inference, we specify transcription factors responsible for the regulation of dynamic developmental processes during lineage diversification. We map lineage differentiation trajectories and find that sinusoid trophoblast giant cells arise from the subpopulation of ectoplacental cone cells. We provide a comprehensive single-cell data resource to shed light on future mechanistic studies of the gene regulatory networks governing hemochorial placentation.

Silk fibroin and sericin differentially potentiate the paracrine and regenerative functions of stem cells through multiomics analysis.

Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, we employed multiomics to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirmed that SF and SS initiated widespread but distinct cellular responses and potentiated the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improved skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibited better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy. This article is protected by copyright. All rights reserved.

The impact of long-term exposure to tacrolimus on chronic kidney disease after lung transplantation: A retrospective analysis from a single transplantation center.

BACKGROUND: Chronic kidney disease (CKD) is a progressive and irreversible complication in lung transplant patients who have received long-term treatment with tacrolimus. This study aimed to verify long-term tacrolimus exposure values in CKD progression. METHODS: We retrospectively analyzed the clinical data of adult lung transplant recipients performed at our center between 2012 and October 2015. Patients who completed the 5-year follow-up period were enrolled in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Eighty patients were analyzed. Compared with baseline (109 ±â€¯38.1 mL/min/1.73 m2), the average eGFR values of our patients gradually decreased during the fifth-year post transplantation (46.5%, 58.3 ±â€¯28.3 mL/min/1.73 m2), and the decline in eGFR values was particularly pronounced in the first year (31.2%, 74.6 ±â€¯28.91 mL/min/1.73 m2). Moreover, 10 (12.7%), 21 (26.9%), 24 (31.2%), 28 (41.2%), and 48 (60%) patients had eGFR <60 mL/min/1.73 m2 at 3, 6, 1, 3, and 5 years after lung transplantation (LT), respectively. A significant negative correlation was found between tacrolimus dose and eGFR 6 months after LT (P = 0.0414). We found no correlation between the serum tacrolimus concentration and CKD progression. CONCLUSION: eGFR constantly decreased and the incidence of CKD increased during the 5-year follow-up period after LT. The tacrolimus dose had a significant negative correlation with eGFR at 6 months after LT. Meanwhile, whole-blood tacrolimus trough concentrations were not correlated with eGFR decline. When possible, lower dosing within 1 year after LT can reduce potential nephrotoxic side effects.

Function of TRPC1 in modulating hepatocellular carcinoma progression.

The liver is the main organ of metabolism in the human body, and it is easy to suffer from hepatitis, cirrhosis, liver cancer, and other diseases, the most serious of which is liver cancer. Worldwide, liver cancer is the most common and deadly malignant tumor, the third leading cause of cancer death in the world. Based on TCGA and ICGC databases, our research discovered the important role of TRPC1 in liver cancer through bioinformatics. The results showed that TRPC1 was over-expressed in hepatocellular carcinoma, and the higher the expression level of TRPC1, the worse the OS and the lower the survival rate. TRPC1 was a risk factor affecting the overall survival probability of hepatocellular carcinoma patients. By analyzing the function of the TRP family in liver cancer, TRPC1 might promote the occurrence of liver cancer by up-regulating common signal pathways in tumors such as tumor proliferation signature, and down-regulating important metabolic reactions such as retinol metabolism. In addition, TRPC1 could promote the development of liver cancer by up-regulating the expression of ABI2, MAPRE1, YEATS2, MTA3, TMEM237, MTMR2, CCDC6, AC069544.2, and NCBP2 genes. These results illustrate that TRPC1 is very valuable in the study of liver cancer.

Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice.

Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we find that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.

Candida albicans enriched in orthodontic derived white spot lesions and shaped focal supragingival bacteriome.

White spot lesions (WSLs) are common enamel infectious diseases in fixed orthodontic treatment, which might attribute to the dysbiosis of oral microbiome. However, the correlation of Candida albicans with oral bacteriome in WSLs still remains unrevealed. This study investigated the carriage of C. albicans and how it shaped the bacterial community in disease or healthy supragingival plaque, to explore the potential role of interkingdom interaction in orthodontic WSLs. In this study, 31 patients with WSLs (WSLs) and 23 healthy patients (Health) undergoing fixed orthodontic treatment were enrolled. The supragingival microbiota in both groups were determined using 16S rRNA gene sequencing. Colonization and abundance of C. albicans in the plaque were determined via culture-dependent and -independent methods. Among WSLs patients, the correlation of C. albicans and bacteriome was analyzed under QIIME2-based bioinformatics and Spearman's correlation coefficient. The raw reads were deposited into the NCBI Sequence Read Archive (SRA) database (Accession Number: SRP404186). Significant differences in microbial diversity as well as composition were observed between WSLs and Health groups. Leptotrichia remarkably enriched in the WSLs group, while Neisseria and Cardiobacterium significantly enriched in the Health group. In addition, 45% of WSLs patients were C. albicans carriers but none in patients without WSLs. Among all WSLs patients, beta diversity and microbial composition were distinguished between C. albicans carriers and non-carriers. In C. albicans carriers, Corynebacterium matruchotii and Streptococcus mutans significantly enriched whereas Saccharibacteria_TM7_G-1 significantly depleted. The abundance of C. albicans was positively associated with bacteria such as Streptococcus mutans, while the negative correlation was detected between C. albicans and several bacteria such as Cardiobacterium hominis and Streptococcus sanguinis. Our study elucidated the distinguished supragingival plaque microbiome between orthodontic patients with and without WSLs. C. albicans frequently existed and enriched in orthodontic derived WSLs. The carriage of C. albicans shape plaque bacterial community in demineralized lesions and might play roles in WSLs pathogenesis.

Spatial-temporal analysis of pulmonary tuberculosis among students in the Zhejiang Province of China from 2007-2020.

Background: Pulmonary tuberculosis (PTB) is a serious chronic communicable disease that causes a significant disease burden in China; however, few studies have described its spatial epidemiological features in students. Methods: Data of all notified PTB cases from 2007 to 2020 in the student population were collected in the Zhejiang Province, China using the available TB Management Information System. Analyses including time trend, spatial autocorrelation, and spatial-temporal analysis were performed to identify temporal trends, hotspots, and clustering, respectively. Results: A total of 17,500 PTB cases were identified among students in the Zhejiang Province during the study period, accounting for 3.75% of all notified PTB cases. The health-seeking delay rate was 45.32%. There was a decreasing trend in PTB notifications throughout the period; clustering of cases was seen in the western area of Zhejiang Province. Additionally, one most likely cluster along with three secondary clusters were identified by spatial-temporal analysis. Conclusion: Although was a downward trend in PTB notifications among students during the time period, an upward trend was seen in bacteriologically confirmed cases since 2017. The risk of PTB was higher among senior high school and above than of junior high school. The western area of Zhejiang Province was the highest PTB risk settings for students, and more comprehensive interventions should be strengthened such as admission screening and routine health monitoring to improve early identification of PTB.

Nitrate determines the bacterial habitat specialization and impacts microbial functions in a subsurface karst cave.

Karst caves are usually considered as natural laboratories to study pristine microbiomes in subsurface biosphere. However, effects of the increasingly detected nitrate in underground karst ecosystem due to the acid rain impact on microbiota and their functions in subsurface karst caves have remained largely unknown. In this study, samples of weathered rocks and sediments were collected from the Chang Cave, Hubei province and subjected to high-throughput sequencing of 16S rRNA genes. The results showed that nitrate significantly impacted bacterial compositions, interactions, and functions in different habitats. Bacterial communities clustered according to their habitats with distinguished indicator groups identified for each individual habitat. Nitrate shaped the overall bacterial communities across two habitats with a contribution of 27.2%, whereas the pH and TOC, respectively, structured bacterial communities in weathered rocks and sediments. Alpha and beta diversities of bacterial communities increased with nitrate concentration in both habitats, with nitrate directly affecting alpha diversity in sediments, but indirectly on weathered rocks by lowering pH. Nitrate impacted more on bacterial communities in weathered rocks at the genus level than in sediments because more genera significantly correlated with nitrate concentration in weathered rocks. Diverse keystone taxa involved in nitrogen cycling were identified in the co-occurrence networks such as nitrate reducers, ammonium-oxidizers, and N2-fixers. Tax4Fun2 analysis further confirmed the dominance of genes involved in nitrogen cycling. Genes of methane metabolism and carbon fixation were also dominant. The dominance of dissimilatory and assimilatory nitrate reduction in nitrogen cycling substantiated nitrate impact on bacterial functions. Our results for the first time revealed the impact of nitrate on subsurface karst ecosystem in terms of bacterial compositions, interactions, and functions, providing an important reference for further deciphering the disturbance of human activities on the subsurface biosphere.

Perspective of People With Type 2 Diabetes Toward Self-management: Qualitative Study Based on Web Crawler Data.

BACKGROUND: The diabetes disease burden in China is heavy, and medical standards such as diabetes guidelines are the core reference guidelines for diabetes management for health care providers and patients. However, patients' guideline compliance is too low, which correlates with the gap between guidelines and patients' self-management needs. Incorporating patient needs into the guideline development would reduce this gap. OBJECTIVE: We sought to capture the needs of patients with diabetes for self-management in everyday situations and to clarify the contradictions and misalignments between medical standards, such as guidelines, and patient needs. METHODS: This study collected crawler-based data from 4 online health communities. We selected 1605 text records collected from Chinese patients with diabetes between March 2020 and July 2020 for analysis. The text analysis applied grounded theory to separate issues that concerned patients into 3 themes, 7 subthemes, and 25 entries. RESULTS: Altogether, 69.03% (1108/1605) of texts were related to issues concerning disease treatment (theme B) and mainly inquired about medication use (B2 and B3; 686/1108, 61.91%), including medication choice, change in medication administration, side effects, and postmedication effects. In addition, 222 (N=1605, 13.8%) texts (theme A) concerned the explanation of disease etiology and knowledge of diabetes, and 275 (N=1605, 17.1%) texts (theme C) discussed lifestyle changes and various restrictions on life brought about by the disease. CONCLUSIONS: Our findings suggest an urgent need to improve diabetes health education and guideline development strategies and to develop health management strategies from a patient perspective to bridge the misalignment between patient needs and current medical standards.

Bacteria and filamentous fungi running a relay race in Daqu fermentation enable macromolecular degradation and flavor substance formation.

As the saccharifying and fermentative agent, medium-temperature Daqu (MT-Daqu) plays an irreplaceable role in the production of strong-flavor Baijiu. Numerous studies have focused on the microbial community structure and potential functional microorganisms, however, little is known about the succession of active microbial community and the formation mechanism of community function during MT-Daqu fermentation. In this study, we presented an integrated analysis of metagenomics, metatranscriptomics, and metabonomics covering the whole fermentation process of MT-Daqu to reveal the active microorganisms and their participations in metabolic networks. The results showed that dynamic of metabolites were time-specific, and the metabolites and co-expressed active unigenes were further classified into four clusters according to their accumulation patterns, with members within each cluster displaying a uniform and clear pattern of abundance across fermentation. Based on KEGG enrichment analysis in co-expression clusters and succession of active microbial community, we revealed that Limosilactobacillus, Staphylococcus, Pichia, Rhizopus, and Lichtheimia were metabolically active members at the early stage, and their metabolic activities were conducive to releasing abundant energy to drive multiple basal metabolisms such as carbohydrates and amino acids. Thereafter, during the high temperature period and at the end of fermentation, multiple heat-resistant filamentous fungi were transcriptionally active populations, and they acted as both the saccharifying agents and flavor compound producers, especially aromatic compounds, suggesting their crucial contribution to enzymatic activity and aroma of mature MT-Daqu. Our findings revealed the succession and metabolic functions of the active microbial community, providing a deeper understanding of their contribution to MT-Daqu ecosystem.

Factors associated with delaying medical care: cross-sectional study of Nebraska adults.

BACKGROUND: Delayed medical care may result in adverse health outcomes and increased cost. Our purpose was to identify factors associated with delayed medical care in a primarily rural state. METHODS: Using a stratified random sample of 5,300 Nebraska households, we conducted a cross-sectional mailed survey with online response option (27 October 2020 to 8 March 2021) in English and Spanish. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals. RESULTS: The overall response rate was 20.8% (n = 1,101). Approximately 37.8% of Nebraskans ever delayed healthcare (cost-related 29.7%, transportation-related 3.7%), with 22.7% delaying care in the past year (10.1% cost-related). Cost-related ever delay was associated with younger age [< 45 years aOR 6.17 (3.24-11.76); 45-64 years aOR 2.36 (1.29-4.32)], low- and middle-income [< $50,000 aOR 2.85 (1.32-6.11); $50,000-$74,999 aOR 3.06 (1.50-6.23)], and no health insurance [aOR 3.56 (1.21-10.49)]. Transportation delays were associated with being non-White [aOR 8.07 (1.54-42.20)], no bachelor's degree [≤ high school aOR 3.06 (1.02-9.18); some college aOR 4.16 (1.32-13.12)], and income < $50,000 [aOR 8.44 (2.18-32.63)]. Those who did not have a primary care provider were 80% less likely to have transportation delays [aOR 0.20 (0.05-0.80)]. CONCLUSIONS: Delayed care affects more than one-third of Nebraskans, primarily due to financial concerns, and impacting low- and middle-income families. Transportation-related delays are associated with more indicators of low socio-economic status. Policies targeting minorities and those with low- and middle-income, such as Medicaid expansion, would contribute to addressing disparities resulting from delayed care.

Covalent Organic Framework/g-C3N4 van der Waals Heterojunction toward H2 Production.

Photocatalytic water splitting into H2 is the most economic and environmentally friendly strategy for H2 production, and rationally constructing a heterojunction retains enormous influence on a photocatalytic system. Herein, 2D/2D covalent organic framework/graphitic carbon nitride (COF/CN) van der Waals heterojunctions were readily prepared via an ultrasonic method for high-efficiency visible-light photocatalytic H2 production. The photocatalytic H2 production performance of optimized COF/CN composites can reach up to 449.64 µmol·h-1, which is approximately 5 times that of pure CN (89.08 µmol·h-1). The characterization and experimental studies reveal that the synergistic effect between COF and CN contributes to promoting the interfacial migration and spatial separation of photoinduced e--h+ pairs, further boosting the photocatalytic hydrogen production activity. This work may open a new window to design and fabricate effective heterojunction photocatalysts for photocatalytic energy conversion.

Archaea and their interactions with bacteria in a karst ecosystem.

Karst ecosystems are widely distributed around the world, accounting for 15-20% of the global land area. However, knowledge on microbial ecology of these systems does not match with their global importance. To close this knowledge gap, we sampled three niches including weathered rock, sediment, and drip water inside the Heshang Cave and three types of soils overlying the cave (forest soil, farmland soil, and pristine karst soil). All these samples were subjected to high-throughput sequencing of V4-V5 region of 16S rRNA gene and analyzed with multivariate statistical analysis. Overall, archaeal communities were dominated by Thaumarchaeota, whereas Actinobacteria dominated bacterial communities. Thermoplasmata, Nitrosopumilaceae, Aenigmarchaeales, Crossiella, Acidothermus, and Solirubrobacter were the important predictor groups inside the Heshang Cave, which were correlated to NH4 + availability. In contrast, Candidatus Nitrososphaera, Candidatus Nitrocosmicus, Thaumarchaeota Group 1.1c, and Pseudonocardiaceae were the predictors outside the cave, whose distribution was correlated with pH, Ca2+, and NO2 -. Tighter network structures were found in archaeal communities than those of bacteria, whereas the topological properties of bacterial networks were more similar to those of total prokaryotic networks. Both chemolithoautotrophic archaea (Candidatus Methanoperedens and Nitrosopumilaceae) and bacteria (subgroup 7 of Acidobacteria and Rokubacteriales) were the dominant keystone taxa within the co-occurrence networks, potentially playing fundamental roles in obtaining energy under oligotrophic conditions and thus maintaining the stability of the cave ecosystem. To be noted, all the keystone taxa of karst ecosystems were related to nitrogen cycling, which needs further investigation, particularly the role of archaea. The predicted ecological functions in karst soils mainly related to carbohydrate metabolism, biotin metabolism, and synthesis of fatty acid. Our results offer new insights into archaeal ecology, their potential functions, and archaeal interactions with bacteria, which enhance our understanding about the microbial dark matter in the subsurface karst ecosystems.

Design and Synthesis of Scopoletin Sulfonate Derivatives as Potential Insecticidal Agents.

(1) Background: Scopoletin and scoparone, two naturally occurring coumarins, have garnered considerable attention and have been introduced to the market in China due to their high insecticidal efficacy and low toxicity. To investigate the structure-activity relationship of these coumarins, a series of scopoletin derivatives with aryl sulfate at C7 and different substitutes at C3 were designed and synthesized, and their insecticidal activity was studied. (2) Methods: A total of 28 new scopoletin derivatives were designed and synthesized. Most target compounds exhibited moderate insecticidal activity against the phytophagous mite Tetranychus cinnabarinus and the brine shrimp Artemia salina. (3) Results: Among these compounds, compounds 5a and 5j possessed the best insecticidal activities against T. cinnabarinus, with LC50 values of 57.0 and 20.0 µg/mL, respectively, whereas that of the control drug was 15.0 µg/mL. Compound 4j exhibited selective insecticidal activities against A. salina, with an LC50 value of 9.36 µg/mL, whereas its LC50 value against T. cinnabarinus was 93.0 µg/mL. The enzymatic inhibitory activity on acetylcholinesterase (AChE) showed a consistent tendency with the insecticidal activity. Further molecular docking analyses predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. (4) Conclusions: In general, a decreased electron cloud density of the Δ3,4 olefinic bond is beneficial for improving the insecticidal activity against both T. cinnabarinus and A. salina. In addition, naphthyl or benzene groups with a sulfate ester at the C7 position could further improve the insecticidal activity against A. salina. AChE was implied to be a site of action for potential insecticidal activity. The results provide insight into the rational design of a new generation of effective coumarin insecticides.

Integration of metabolomics and transcriptomics analyses reveals sphingosine-1-phosphate-mediated S1PR2/PI3K/Akt pathway involved in Talaromyces marneffei infection of macrophages.

Talaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic profiles and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most influential. Verification experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have significantly increased in the T. marneffei infection group (p < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis.

Evaluation of BioFire Respiratory Panel 2 plus for Detection of Bordetella pertussis in Nasopharyngeal Swab Specimens from Children with Clinically Suspected Pertussis.

The objective of this study was to compare the performances of BioFire Respiratory Panel 2 (RP2) plus, quantitative real-time PCR (qPCR), and culture for the detection of Bordetella pertussis in nasopharyngeal swab (NPS) specimens. Consecutive NPS specimens were collected from patients with clinically suspected pertussis from 1 March 1 to 31 July 2018 in Shenzhen Children's Hospital. All the specimens were tested in parallel by RP2 plus, qPCR, and culture methods. A total of 464 children were enrolled in this study. The positive pertussis rates of culture, RP2 plus, and qPCR were 23.1%, 39.0%, and 38.4%, respectively. Compared to the combined reference standard, the sensitivity, specificity, positive predictive value, and negative predictive values were, respectively, 56.6% (95% confidence interval [CI], 49.2 to 63.7%), 100% (98.3 to 100%), 100% (95.7 to 100%), and 77.0% (72.2 to 81.2%) for culture, 89.9% (84.5 to 93.7%), 96.0% (92.8 to 97.9%), 93.9% (89.1 to 96.8%), and 93.3% (89.5 to 95.8%) for RP2 plus, and 86.8% (80.9 to 91.1%), 94.9% (91.4 to 97.1%), 92.1% (86.9 to 95.5%), and 91.3% (87.2 to 94.2%) for qPCR. The most prevalent codetected pathogen was human rhinovirus/enterovirus (n = 99, 52.4%), followed by parainfluenza virus (n =32, 16.9%) and respiratory syncytial virus (n = 29, 15.3%), in children with B. pertussis present, which was consistent with the top three pathogens previously found in children with B. pertussis absent. Turnaround times for RP2 plus, qPCR, and culture were 2 h, 8 h, and 120 h, respectively. RP2 plus quickly and accurately detected B. pertussis, providing valuable information for an early clinical diagnosis and optimal choice of therapy. IMPORTANCE In recent years, there have been some epidemic or local outbreaks of pertussis in countries with high vaccination rates. One of the crucial factors in controlling pertussis is early diagnosis, which is based on specific laboratory measurements, including culture, serological tests, and PCR assays. Compared to culture and serological tests, PCR is more suitable for clinical application, with a fast detection speed of several hours independent of the disease stage and individual vaccination status. BioFire Respiratory Panel 2 plus, a multiplex PCR assay for simultaneously detecting 22 respiratory pathogens, facilitates the quick detection of Bordetella pertussis and coinfecting respiratory pathogens. It also provides valuable information for an early clinical diagnosis and optimal choice of therapy for children with clinically suspected pertussis.