Search

Abstract Investigating the anti‐inflammatory effects of bioactive components present in cold‐pressed rapeseed oil through the use of network pharmacology and molecular docking methods. The components of cold‐pressed rapeseed oil were identified by liquid chromatography‐mass spectrometry. We then conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using bioinformatics databases on overlapping targets affected by active components and inflammation. Finally, molecular docking was used to predict the interactions between core components and key targets. Analysis identified 13 phenols, four steroids, and one retinoid in cold‐pressed rapeseed oil, with 143 overlapping targets related to inflammation. Bioinformatics analysis revealed that 25‐Hydroxycholesterol, Rosmarinic acid, 9‐cis‐Retinoic acid, Soyasapogenol B and α‐Tocopherol in cold‐pressed rapeseed oil could play a positive role in treating inflammation. They achieved this by regulating key targets (MMP9, EGFR, AKT1, ESR1, and PTGS2) involved in the peroxisome proliferator‐activated receptor signaling pathway and other related pathways. The molecular docking binding energy of the core components and the key targets were less than −5.0 kcal/mol, indicating that the components and the targets can be stably bound. This result indicated that the active components found in cold‐pressed rapeseed oil may exert an anti‐inflammatory effect through a synergistic mechanism involving multicomponent, multitarget and multipathway interactions.

Background: Doxorubicin and cisplatin are both first-line chemotherapeutics for osteosarcoma (OS) treatment. However, the efficacy of doxorubicin/cisplatin chemotherapy varies considerably. Thus, identifying an efficient diagnostic biomarker to distinguish patients with good and poor responses to doxorubicin/cisplatin chemotherapy is of paramount importance. Methods: To predict the efficacy of doxorubicin/cisplatin chemotherapy, we analyzed the differentially expressed proteins in 37 resected OS samples, which were categorized into the primary group (PG), the recurrent group (RG) and the metastatic group (MG). The characteristics of the enriched differentially expressed proteins were assessed via GO and KEGG analyses. Protein‒protein interactions were identified to determine the relationships among the differentially expressed proteins. Receiver operating characteristic (ROC) curve analyses were performed to explore the clinical significance of the differentially expressed proteins. Parallel reaction monitoring (PRM) was used to validate the candidate proteins. Immunohistochemical (IHC) staining was performed to confirm the expression of cathepsin (CTSG) in patients with good and poor response to doxorubicin/cisplatin. Results: A total of 9458 proteins were identified and quantified, among which 143 and 208 exhibited significant changes (|log2FC|>1, p < 0.05) in the RG and MG compared with the PG, respectively. GO and KEGG enrichment led to the identification of neutrophil extracellular traps (NETs). ROC curve analyses revealed 74 and 86 proteins with areas under the curve greater than 0.7 in the RG and MG, respectively. PRM validation revealed the statistical significance of CTSG, which is involved in NET formation, at the protein level in both the RG and MG. IHC staining of another cohort revealed that CTSG was prominently upregulated in the poor response group after treatment with doxorubicin/cisplatin. Conclusion: CTSG and its associated NETs are potential biomarkers with which the efficacy of doxorubicin/cisplatin chemotherapy could be predicted in OS patients.

Moraxella catarrhalis (M. catarrhalis), once considered as a harmless commensal bacterium, is now recognized as a significant pathogen associated with human mucosal infection. Hence, development of rapid, accurate, and user-friendly detection method is crucial for effective control and management of M. catarrhalis infections. Here, we introduce the M. catarrhalis MCDA-FRT assay, a novel diagnostic approach based on multiple cross displacement amplification (MCDA) for the visual and fluorescent (FRT) detection of M. catarrhalis. This innovative method amplifies the target sequence through MCDA reaction and provides results through the visual observation of a fluorescent signal when exposed to blue light. The generation of the fluorescent signal is facilitated by the cleavage of the restriction endonuclease Nb.BsrDⅠ. The M. catarrhalis MCDA-FRT assay can efficiently detect M. catarrhalis at a temperature of 65 °C in 40 min. It exhibits a remarkable sensitivity of 35 fg of M. catarrhalis genomic DNA, with a specificity of 100%. Furthermore, the assay accurately identified all M. catarrhalis-infected clinical samples tested. In conclusion, the M. catarrhalis MCDA-FRT assay showcases outstanding performance in terms of simplicity, sensitivity, and specificity, which can be used as a promising diagnostic tool for the swift and reliable detection of M. catarrhalis in both field and basic medical settings.

Study area: Hebei Province, China Study focus: Accurate assessment of sector-specific groundwater withdrawals (GWW) is fundamental for targeted groundwater management policies, particularly in regions suffering from severe groundwater over-extraction. Due to the lack of statistical data and the coarse resolution of water supply patterns and GWW, previous studies couldn’t well quantify the GWW where the impact of inter-basin water diversion projects was also neglected. Here we proposed a methodology to simulate sectoral GWW based on flux balance in consideration of the influence of inter-basin water diversion projects. New hydrological insights for the study region: A case study in Hebei Province, where groundwater is severely over extracted, was used to validate our methodology. Our results showed that the gridded GWW calculations are well aligned with the statistical data from the Hebei Water Resources Bulletin (WRB) at both provincial and municipal levels, with correlation coefficients (R) above 0.9 and normalized root mean squared errors (NRMSE) below 0.1. County-level GWW estimates also match with data from the Department of Water Resources of Hebei Province for 2013 and 2018, with NRMSE around 0.2. Piecewise Linear Regression (PLR) analysis of sectoral GWW further reveals that GWW is quickly declined when water diversion projects or policies are implemented. Together our findings underscore a significant role of water resource engineering and policies in alleviating groundwater over-extraction.

Abstract Understanding the impact of climate change on the geographical distribution of species is a fundamental requirement for biodiversity conservation and resource management. Quercus oxyphylla, an evergreen oak endemic to China, plays a crucial role in maintaining the ecological stability in subtropical regions and high economic value attributed to its dark and high‐density heartwood, but the existing resources are close to endangered. Currently, limited knowledge exists regarding its distribution and potential influences of climate change on suitable areas. This study utilized 63 occurrence records and Biomod2 platform, to predict changes in suitable areas for Q. oxyphylla under future climate change. The results revealed that (1) Q. oxyphylla showed a pattern of three disjunctive geographical centers in the eastern subregion of subtropical evergreen broad‐leaved forest region (IVA): Qinling‐Daba Mountains, Nanling Mountains and Wuyi Mountains center. Currently, the highly suitable areas concentrated in two zones divided by the Yangtze River, that is, the northern subtropical evergreen and deciduous broad‐leaved forest zone (IVAii) and the mid‐subtropical evergreen broad‐leaved forest zone (IVAi). (2) The temperature‐related variables, such as annual temperature range (Bio7), the mean diurnal range (Bio2), and annual mean temperature (Bio1), were identified as the key determinants of the distribution pattern. Because of its considerable climatic variations in temperature and water conditions, Q. oxyphylla's habitat displayed a wider climate niche and strong physiological tolerance to climate change. (3) Under future climate scenarios, the suitable area of the species was expected to overall expand with significant regional differences. The suitable area in IVAi was expected to expand significantly northward while that in IVAii was expected to gradually shrink. To address the impact of climate change, it is necessary to develop conservation plans focused around the three distribution centers, implement localized and regional conservation policies, and conduct educational outreach among local people.

Chinese Kunming dog (CKD) is a working breed widely used by army, customs and police across the country. To better evaluate a breeding population's potential working performance and implement selective breeding for future offspring, a temperament test with five subsets, including following to trainer (FO), reaction to stranger (RS), tease by towel (TT), chase and fetch (CF) and tug of war (TW), was annually operated by the Kunming Police Dog Base since 2019. To fully utilize this behavioral data, 92 breeding animals of CKDs were genotyped by a 50K SNP chip, and a GWAS method supporting repeated measurement was adopted to estimate heritabilities and explore genetic variants associated with the five subsets. The heritabilities estimated for the five subsets ranged from 0,03 to 0.14, which showed a possibility for genetic improvement. Meanwhile, in total seven novel SNPs were identified associated with subsets FO, TT, CF and TW. In addition to that five of the seven loci are separately located within ACOT11, PRDM16, SAMD12, CPA1 and ENSCAFG00000023173 genes. Nevertheless, genetic effects of these novel loci on dog temperament should be further validated by a larger dataset in the future.

Mycoplasma pneumoniae is a significant pathogen responsible for community-acquired pneumonia, predominantly affecting children and adolescents. Here, we devised a rapid method for M. pneumoniae that combined multiple cross displacement amplification (MCDA) with real-time fluorescence technology. A set of ten primers, which were specifically designed for M. pneumoniae detection, were employed in a real-time fluorescence MCDA reaction. Of these, one primer incorporated a restriction endonuclease recognition sequence, a fluorophore, and a quencher, facilitating real-time fluorescence detection. The real-time (RT)-MCDA reactions were monitored in a simple real-time fluorescence instrument and conducted under optimised conditions (64°C for 40 min). The detection limit of the M. pneumoniae RT-MCDA assay for genomic DNA extracted from M. pneumoniae culture was down to 43 fg/µl. This assay accurately identified M. pneumoniae strains without cross-reacting with other bacteria. To validate its practical application, we tested the M. pneumoniae RT-MCDA assay using genomic DNA extracted from clinical samples. The assay’s detection capability proved comparable with real-time PCR, MCDA-based biosensor detection, and visual inspection under blue light. The entire process, including rapid DNA extraction and real-time MCDA detection, was completed within 1 h. Overall, the M. pneumoniae RT-MCDA assay reported here is a simple and effective diagnostic tool for rapid M. pneumoniae detection, which holds significant potential for point-of-care testing and in resource-limited regions.

Background: Non-invasive prenatal tests (NIPT) are used to screen for trisomy 21, 18, and 13. This study investigated NIPT performance and the clinical significance of its results. Methods: Pregnant women (n = 282,911) participating in a free NIPT (April 2018–December 2021) were screened for common trisomies, and the results were retrospectively analyzed. NIPT performance was evaluated by its positive predictive value (PPV), sensitivity, and specificity. Results were analyzed using number, percentage, and chi-squared/t-test analyses. Results: After NIPT screening, patients with common trisomies (n = 746) included 457 with T21, 160 with T18, and 129 with T13. Seven false negative cases were identified. High PPV (86.81 %, 56.81 %, 18.18 %), sensitivity (99.25 %, 98.33 %, 100.00 %), and specificity (99.98 %, 99.98 %, 99.97 %) values were detected for trisomy 21, 18, and 13, respectively. The PPVs of common trisomies were significantly different between pregnant women older than 35 (85.53 %, 136/159) and those aged 35 or younger (58.90 %, 311/528) (χ2 = 125.02, P = 2.20e-16). As the NIPT uptake increased from 2018 to 2021, live-born birth defect incidence decreased. Conclusion: NIPT performed well in screening for T21, T18, and T13. Our discoveries offer an important and useful guideline in laboratory and clinical genetic counseling.

Molecular techniques of nucleic acid testing recommended by the World Health Organization (WHO) for the Mycobacterium tuberculosis (MTB) detection were considered to have the potential access to the accurate tuberculosis (TB) notifications. In this study, a new method, which coupled real-time (rt) fluorescence technique with multiple cross displacement amplification (MCDA), was developed for the rapid, sensitive and specific detection of MTB (termed MTB-rt-MCDA). According to the principle of the rt-MCDA test, a set of ten primers were designed for the MCDA reaction, of which one was engineered with a restrictive endonuclease recognition site, a fluorophore and a quencher for achieving the real-time fluorescence detection. MTB-rt-MCDA test was conducted under the optimized conditions (67 °C, 40 min) on the real-time fluorescence platform. The MTB-rt-MCDA assay accurately identified the MTB strains with no cross reaction with other bacteria. The lowest detectable genomic DNA concentration of the MTB-rt-MCDA assay was 25 fg/μl. We employed the genomic DNA templates extracted from sputum of clinical cases for validating the practical applicability of this assay, and the detection power of the MTB-rt-MCDA assay was comparable to that of the Xpert method and MCDA-based biosensor detection and superior to smear microscope method. The complete process of the MTB-rt-MCDA assay, including rapid extraction of DNA and rt-MCDA test, takes less than 1 h. In conclusion, the presented MTB-rt-MCDA assay provided an effective and simple option for the rapid screening of MTB infection.

Moraxella catarrhalis (M. catarrhalis) was an underestimated respiratory infection pathogen that has been largely overlooked. The limited availability of rapid and sensitive detection methodologies has hindered M. catarrhalis diagnostic in clinical settings and contributed to its underestimation. To address this issue, we devised two recombinase polymerase amplification (RPA)-based assays for rapid, sensitive and reliable detection of M. catarrhalis, termed M. catarrhalis-RPA-Flu and M. catarrhalis-RPA-LFB, which utilized fluorescence and nanoparticle-based lateral flow biosensor (LFB) for reporting the detection results, respectively. In both assays, the specific copB gene of M. catarrhalis was amplified at 37°C for only a period of 20 minutes. In M. catarrhalis-RPA-Flu system, the detection results were analyzed by either using a real-time fluorescent detector or by direct observation using the naked eye under blue light, while, in M. catarrhalis-RPA-LFB system, biosensors were used for interpreting the results without any specialized instruments. Both methods were able to finalize the entire detection process within a duration of 40 minutes, detect down to 35 fg genomic DNA per test, and correctly differentiate M. catarrhalis from non-M. catarrhalis strains. The feasibility of both techniques was validated by analyzing 96 BALF (Broncho alveolar lavage fluid) samples in clinical settings. Collectively, the newly developed two RPA-based assays exhibit great potential for rapid and accurate identification of M. catarrhalis in standard microbiology laboratories as well as diagnosis of M. catarrhalis infection in clinical settings.

Moraxella catarrhalis (M. catarrhalis) was an important pathogen closely associated with respiratory tract infections. We employed the loop-mediated isothermal amplification (LAMP) coupled with nanoparticle-based lateral flow biosensor (LFB) and fluorescence testing technique for formulating two diagnostic methods for M. catarrhalis detection, termed M. catarrhalis-LAMP-LFB assay and M. catarrhalis-LAMP-FRT, respectively. The M. catarrhalis-LAMP-LFB system incorporated the use of biotin-14-dCTP and a forward loop primer (LF) with a hapten at the 5′ end. This design in LAMP reaction enabled the production of double-labeled products that could be effectively analyzed using the lateral flow biosensor (LFB). For the M. catarrhalis-LAMP-FRT assay, the LF was modified with a sequence at 5′ end, and a fluorophore, as well as a black hole quencher, were strategically labeled at the 5′ end and within the middle of the new LF. The restriction endonuclease Nb.BsrDI could accurately recognize and cleave the newly synthesized double-strand terminal sequences, resulting in the separation of the fluorophore from the black hole quencher and releasing fluorescence signals. Both assays have been proven to be highly sensitive and specific, capable of detecting genomic DNA of M. catarrhalis at concentrations as low as 70 fg, with no cross-reactivity observed with non-M. catarrhalis pathogens. Furthermore, both methods successfully identified M. catarrhalis in all clinical samples within 1 h that were confirmed positive by real-time PCR, exhibiting superior sensitivity than conventional culture methods. Herein, the newly developed two LAMP-based assays were rapid and reliable for M. catarrhalis detection and hold significant promise for deployment in point-of-care (POC) settings.

BackgroundMental health risks associated with the aftermath of the COVID-19 pandemic are often overlooked by the public. The aim of this study was to investigate the effects of the COVID-19 pandemic on depression and anxiety disorders in China.MethodsStudies were analyzed and extracted in accordance with the PRISMA 2020 flowchart. The studies were screened and extracted using electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov according to the predefined eligibility criteria. The Cochrane Review Manager software 5.3.1 was used for data analysis and the risk of bias assessment.ResultsAs of 2023, a total of 9,212,751 Chinese have been diagnosed with COVID-19 infection. A total of 913,036 participants in 44 studies were selected following the eligibility criteria, the statistical information of which was collected for meta-analysis. The pooled prevalence of depression and anxiety were 0.31 (95% CI: 0.28, 0.35; I2 = 100.0%, p

Abstract Objective Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. Methods Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. Results The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. Conclusion The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

The underwater channel is bilateral, heterogeneous, uncertain, and exhibits multipath transmission, sound line curvature, etc. These properties complicate the structure of the received pulse, causing great challenges in direct signal identification for ranging purposes and impacts on back-end data processing, even accurate acoustic positioning. Machine learning (ML) combined with underwater acoustics has emerged as a prominent area of research in recent years. From a statistical perspective, ML can be viewed as an optimization strategy. Nevertheless, the existing ML-based direct-signal discrimination approaches rely on independent assessment, utilizing a single sensor (beacon or buoy), which is still insufficient for adapting to the complex underwater environment. Thus, discrimination accuracy decreases. To address the above issues, an accurate CW direct signal detection approach is performed using the decision tree algorithm, which belongs to ML. Initially, the pulse parameter characteristics in the underwater multipath channel are investigated and the parameter models are built. Then, based on multi-sensor localization performance feedback, fusion characteristics for diverse pulse are created. Next, the pulse parameter characteristics are preprocessed to mitigate the impact of varying magnitudes and units of magnitude on data processing. Then, the decision tree is built to obtain the desired output results and realize accurate recognition of the ranging direct signals. Finally, the feasibility and reliability of this paper’s method are verified by computer simulation and field testing.

Abstract Background Hair follicle stem cells (HFSCs) are considered as a promising cell type in the stem cell transplantation treatment of neurological diseases because of their rich sources, easy access, and the same ectoderm source as the nervous system. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that shows neuroprotective function in ischemic stroke. Here we assessed the therapeutic effects of HFSCs on ischemic stroke injury and the synthetic effect of HGF along with HFSCs. Methods Rat HFSCs were intravenously transplanted into a middle cerebral artery ischemia/reperfusion (I/R) rat model. Neurological scoring and TTC staining were performed to assess the benefits of HFSC transplantation. Inflammatory cytokines, blood–brain barrier integrity and angiogenesis within penumbra were estimated by Western blot and immunohistochemistry. The differentiation of HFSCs was detected by immunofluorescence method 2 weeks after transplantation. Results HFSC transplantation could significantly inhibit the activation of microglia, improve the integrity of blood–brain barrier and reduce brain edema. Moreover, the number of surviving neurons and microvessels density in the penumbra were upregulated by HFSC transplantation, leading to better neurological score. The combination of HFSCs and HGF could significantly improve the therapeutic benefit. Conclusion Our results indicate for the first time that HGF modified HFSCs can reduce I/R injury and promote the neurological recovery by inhibiting inflammatory response, protecting blood–brain barrier and promoting angiogenesis.

Although previous studies have reported the use of metabolomics for infectious diseases, little is known about the potential function of plasma metabolites in children infected with Mycoplasma pneumoniae (MP). Here, a combination of liquid chromatography-quadrupole time-of-flight mass spectrometry and random forest-based classification model was used to provide a broader range of applications in MP diagnosis. In the training cohort, plasma from 63 MP pneumonia children (MPPs), 37 healthy controls (HC) and 29 infectious disease controls (IDC) was collected. After multivariate analyses, 357 metabolites were identified to be differentially expressed among MPP, HC and IDC groups, and 3 metabolites (568.5661, 459.3493 and 411.3208) had high diagnostic values. In an independent cohort with 57 blinded subjects, samples were successfully classified into different groups, demonstrating the reliability of these biomarkers for distinguishing MPPs from controls. A metabolomic signature analysis identified major classes of glycerophospholipids, sphingolipids and fatty acyls were increased in MPPs. These markedly altered metabolites are mainly involved in glycerophospholipid and sphingolipid metabolism. As the ubiquitous building blocks of eukaryotic cell membranes, dysregulated lipid metabolism indicates damage of the cellular membrane and the activation of immunity in MPPs. Moreover, lipid metabolites, differentially expressed between severe and mild MPPs, were correlated with the markers of extrapulmonary complications, suggesting that they may be involved in MPP disease severity. These findings may offer new insights into biomarker selection and the pathogenesis of MPP in children.

Pseudomonas aeruginosa (P. aeruginosa) is an important bacterial pathogen involved in a wide range of infections and antimicrobial resistance. Rapid and reliable diagnostic methods are of vital important for early identification, treatment, and stop of P. aeruginosa infections. In this study, we developed a simple, rapid, sensitive, and specific detection platform for P. aeruginosa infection diagnosis. The method integrated recombinase polymerase amplification (RPA) technique with clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR-associated protein 12a (Cas12a) biosensing system and was termed P. aeruginosa–CRISPR–RPA assay. The P. aeruginosa–CRISPR–RPA assay was subject to optimization of reaction conditions and evaluation of sensitivity, specificity, and clinical feasibility with the serial dilutions of P. aeruginosa genomic DNA, the non–P. aeruginosa strains, and the clinical samples. As a result, the P. aeruginosa–CRISPR–RPA assay was able to complete P. aeruginosa detection within half an hour, including RPA reaction at 42°C for 20 min and CRISPR-Cas12a detection at 37°C for 10 min. The diagnostic method exhibited high sensitivity (60 fg per reaction, ~8 copies) and specificity (100%). The results of the clinical samples by P. aeruginosa–CRISPR–RPA assay were consistent to that of the initial result by microfluidic chip method. These data demonstrated that the newly developed P. aeruginosa–CRISPR–RPA assay was reliable for P. aeruginosa detection. In summary, the P. aeruginosa–CRISPR–RPA assay is a promising tool to early and rapid diagnose P. aeruginosa infection and stop its wide spread especially in the hospital settings.

Mycoplasma pneumoniae (MP) is an important causative agent of morbidity and mortality among all age groups, especially among patients of extreme ages. Improved and readily available tests for accurate, sensitive and rapid diagnosis of MP infection is sorely needed. Here, we developed a CRISPR-Cas12b-based detection platform on the basis of recombinase polymerase amplification (RPA) for rapid, simple, and accurate diagnosis of MP infection, named MP-RPA-CRISPR. The RPA was employed for amplifying the community-acquired respiratory distress syndrome (CARDS) toxin gene of MP strains at the optimal reaction temperature 37°C. The resulting amplicons were decoded by the CRISPR-Cas12b-based detection platform, which was interpreted by real-time PCR system and by naked eye under blue light. The MP-RPA-CRISPR can detected down to 5 fg of genomic DNA templates of MP strains and accurately distinguish MP strains from non-MP strains without any cross-reactivity. A total of 96 bronchoalveolar lavage fluid (BALF)samples collected from patients suspected of respiratory infection were used to evaluate the clinical performance of the MP-RPA-CRISPR assay. As a result, our assay accurately diagnosed 45 MP-infected samples and 51 non-MP infected sample, and the results obtained from MP-RPA-CRISPR were consistent with microfluidic chip technology. In conclusion, our MP-RPA-CRISPR assay is a simple, rapid, portable and highly sensitive method to diagnose MP infection, which can be used as a promising tool in a variety of settings including clinical, field, and resource-limited aeras.

Incorporating the process-induced material anisotropy into design framework of additively manufactured lattice structures is crucial to ensure the accuracy of design and analysis models. This work proposes an analytical approach to design stretching-dominated truss lattices with tailored elastic properties, including isotropic elasticity, tailored zero/negative Poisson’s ratios, tailored Young’s moduli ratios along specified directions. The transversely isotropic elasticity is adopted to represent the micro lase powder bed fusion (LPBF) process-induced anisotropy of base materials. The lattices are designed through combination of elementary bars with appropriate volume fractions. An analytical homogenization theory is established to determine elastic constants of combined lattices. An analytical design approach is proposed to obtain elastically isotropic truss lattices. A traversal searching is performed to determine ranges of Young’s moduli, Poisson’s ratios of combined lattices, and find most manufacturable ones with tailored Young’s moduli ratios and Poisson’s ratios. Finite element analysis reveals all designed lattices from anisotropic materials achieve better agreements to design targets than those designed from isotropic materials, thus validating the superiority of the proposed method. The lattices with isotropic elasticity, tailored zero/negative Poisson’s ratios are fabricated in stainless steel 316L via micro-LPBF, and quasi-static compression experiments are performed to further validate the proposed design approach.

Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is the second leading cause of death after COVID-19 pandemic. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform for tuberculosis diagnosis, termed MTB-MCDA-CRISPR. MTB-MCDA-CRISPR pre-amplified the specific sdaA gene of MTB by MCDA, and the MCDA results were then decoded by CRISPR-Cas12a-based detection, resulting in simple visual fluorescent signal readouts. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the sdaA gene of MTB. The optimal temperature for MCDA pre-amplification is 67°C. The whole experiment process can be completed within one hour, including sputum rapid genomic DNA extraction (15 minutes), MCDA reaction (40 minutes), and CRISPR-Cas12a-gRNA biosensing process (5 minutes). The limit of detection (LoD) of the MTB-MCDA-CRISPR assay is 40 fg per reaction. The MTB-MCDA-CRISPR assay does not cross reaction with non-tuberculosis mycobacterium (NTM) strains and other species, validating its specificity. The clinical performance of MTB-MCDA-CRISPR assay was higher than that of the sputum smear microscopy test and comparable to that of Xpert method. In summary, the MTB-MCDA-CRISPR assay is a promising and effective tool for tuberculosis infection diagnosis, surveillance and prevention, especially for point-of-care (POC) test and field deployment in source-limited regions.

Summary: Respiratory syncytial virus (RSV) is an important pathogen causing pneumonia in children. Few studies have used multi-omics data to investigate the pathogenies of RSV pneumonia. Here, metabolomics was first used to identify potential biomarkers for RSV diagnosis. In the training cohort, serum from 36 healthy controls (HCs), 45 RSV pneumonia children, and 32 infectious disease controls (IDCs) were recruited. After analyses, six metabolites had potential diagnostic value. Using an independent cohort of 49 subjects, two biomarkers (neuromedin N and histidyl-proline diketopiperazine) were validated. Next, multi-omics analysis were applied to analyze the pathogenies of RSV pneumonia. Accumulation of collagen in the serum of RSVs indicated that RSV infection could lead to increased levels of soluble collage. Activation of the complement system and imbalance in lipid metabolism were also observed in RSV patients. The multi-omics analysis presented here revealed the signature protein and metabolite changes in serum caused by RSV infection.

The ongoing outbreak of the monkeypox, caused by monkeypox virus (MPXV), has been a public health emergency of international concern, indicating an urgent need for rapid and sensitive MPXV detection. Here, we designed a diagnostic test based on loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor(LFB)for diagnosis of MPXV infection, termed MPX-LAMP-LFB. A set of six LAMP primers was designed based the ATI gene of MPXV, and LAMP amplification of MPXV templates was performed at 63°C for only 40 min. The results were rapidly and visually decided using the LFB test within 2 min. The MPX-LAMP-LFB assay can specifically detect MPXV strains without cross-reaction with non-MPXV pathogens. The sensitivity of the MPX-LAMP-LFB assay is as low as 5 copies/μl of plasmid template and 12.5 copies/μl of pseudovirus in human blood samples. The whole process of the MPX-LAMP-LFB assay could be completed ~1 h, including rapid template preparation (15 min), LAMP reaction (40 min)and result reporting (

Background: Neutrophil extracellular traps (NETs) closely link inflammation and thrombosis. The immune-related GTPase family M protein (IRGM) and its ortholog of mouse IRGM1 are positively correlated with plaque rupture during atherosclerosis process. However, whether and how IRGM/IRGM1 affects NETs formation and atherosclerotic thrombosis remains unknown, which will further promote the development of antithrombotic treatment tools. Methods: The thrombi images, platelet activation makers and NETs makers were detected in the serum of STEMI patients and controls. To futher investigate IRGM/IRGM1 affects NETs formation and atherothrombosis in vivo, ApoE-/-Irgm1+/- and ApoE-/- mice received diets rich in fat and 2.5% FeCl3 was then used to induce experimental arterial thrombosis in an atherosclerosis background. In vitro, PMA and thrombin were used to stimulate neutrophils and platelets, respectively, and the expression of IRGM/IRGM1 were modified. To reveal the molecular mechanisms, MAPK-cPLA2 signals inhibitors were used. Results: Serum IRGM was positively correlated with PF4 and neutrophil elastase. Subsequently, Irgm1 deficient mice have a longer occlusion time and lower growth rate. In vitro, as expected, IRGM/Irgm1 deficiency inhibits platelet activation and platelet-neutrophil interaction. More importantly, IRGM promoted NETs production through activating MAPK-cPLA2 signals in PMA stimulated neuropils, whereas inhibiting the production of NETs eliminated the difference in platelet activation and thrombosis caused by IRGM/Irgm1 modification in vivo and vitro. Similarly, inhibition of platelet activation also eliminated the influence of IRGM/Irgm1 modification on NETs production. Conclusions: Overall, our data indicate that IRGM/Irgm1 deficiency in neuropils inhibits the intense interaction between neutrophils and platelets, and ultimately inhibits thrombosis.

Mycoplasma pneumoniae (MP), which is responsible for a majority of community-acquired pneumonia (CAP) in children, has been largely underestimated. Here, we coupled multiple cross displacement amplification (MCDA) technique with CRISPR-Cas12a-based biosensing system to design a novel detection platform termed MP-MCDA-CRISPR assay for MP infection diagnosis and clinical application. The MP-MCDA-CRISPR assay amplified the CARDS gene of MP by MCDA method, followed by trans-cleavage of the reporter molecular upon the formation of CRISPR-Cas12a-gRNA-target DNA complex, which was confirmed by the release of fluorescent signals. A set of standard MCDA primers, an engineered CP1 primer, a quenched fluorescent ssDNA reporter, and a gRNA were designed targeting the CARDS gene of MP. The optimal temperature for MCDA pre-amplification is 64°C, and the time for CRISPR-Cas12a-gRNA biosensing process is 5 min. The limit of detection (LoD) of the MP-MCDA-CRISPR assay is 50 fg per reaction without any cross-reaction with other non-MP pathogens. The MP-MCDA-CRISPR assay accurately identified the 50 real time-PCR positive clinical samples and 78 negative ones. Taken together, the MP-MCDA-CRISPR assay designed here is a promising diagnostic tool for point-of care (POC) testing of MP infection.

ObjectiveFinding target genes and target pathways of existing drugs for drug repositioning in multiple sclerosis (MS) based on transcriptomic changes in MS immune cells.Materials and MethodsBased on transcriptome data from Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) in MS patients without treatment were identified by bioinformatics analysis according to the type of immune cells, as well as DEGs in MS patients before and after drug administration. Hub target genes of the drug for MS were analyzed by constructing the protein-protein interaction network, and candidate drugs targeting 2 or more hub target genes were obtained through the connectivity map (CMap) database and Drugbank database. Then, the enriched pathways of MS patients without treatment and the enriched pathways of MS patients before and after drug administration were intersected to obtain the target pathways of the drug for MS, and the candidate drugs targeting 2 or more target pathways were obtained through Kyoto Encyclopedia of Genes and Genomes (KEGG) database.ResultsWe obtained 50 hub target genes for CD4+ T cells in Fingolimod for MS, 15 hub target genes for Plasmacytoid dendritic cells (pDCs) and 7 hub target genes for Peripheral blood mononuclear cells (PBMC) in interferon-β (IFN-β) for MS. 6 candidate drugs targeting two or more hub targets (Fostamatinib, Copper, Artenimol, Phenethyl isothiocyanate, Aspirin and Zinc) were obtained. In addition, we obtained 4 target pathways for CD19+ B cells and 15 target pathways for CD4+ T cells in Fingolimod for MS, 7 target pathways for pDCs and 6 target pathways for PBMC in IFN-β for MS, most of which belong to the immune system and viral infectious disease pathways. We obtained 69 candidate drugs targeting two target pathways.ConclusionWe found that applying candidate drugs that target both the “PI3K-Akt signaling pathway” and “Chemokine signaling pathway” (e.g., Nemiralisib and Umbralisib) or applying tyrosine kinase inhibitors (e.g., Fostamatinib) may be potential therapies for the treatment of MS.

Micro laser powder bed fusion (μLPBF), for the first time, enables fabrication of low-density triply periodic minimal surface (TPMS) shell lattices with smaller feature size. However, the understandings on the mechanical responses of lightweight TPMS structures by μLPBF are yet to be updated. Herein, stainless steel 316L TPMS shell lattices (i.e., Primitive (P), Diamond (D) and Gyroid (G)) with different shell thicknesses and cell orientations were fabricated by µLPBF. Low-density TPMS structures with shell thickness as small as ∼100 μm and relative density ∼5 % were realized. Quasi-static compression tests and finite element modelling were conducted to study their compressive responses. Their light-weighting potential related to the scaling behavior of mechanical properties as a function of relative density was analyzed. Results show with increasing relative density, the deformation mechanism transforms from localized collapse to homogeneous bulk deformation. P-type TPMS exhibits the highest anisotropy of stiffness, strength and energy absorption capability, while G-type TPMS is near-isotropic. [100] oriented d-type TPMS shows the highest strength and best light-weighting potential. Compared with conventional LPBF, the µLPBF TPMS structures demonstrate higher mechanical properties and superior light-weighting potential. Overall, this work highlights the superiority of the µLPBF technology in fabricating lightweight TPMS structures for mechanical applications.

Haemophilus influenzae is an opportunistic pathogen usually causing bacteremia, meningitis, and pneumonia in children. Here, we developed a method based on multiple cross displacement amplification (MCDA) method and real-tme fluorescence technique for rapid detection of H. influenzae. A set of 10 primers was designed for the H. influenzae real-time MCDA reaction, and a core primer was modified with a restriction endonuclease recognition sequence, a fluorescent, and a quencher according to the principle of the real-time MCDA assay. The H. influenzae real-time MCDA reactions were performed using a fluorescence instrument at 63°C for 40 min. The H. influenzae real-time MCDA assay can specifically detect H. influenzae without any cross-reaction with other bacteria as our results confirmed. The sensitivity of our assay is as low as 10 CFU per reaction. To validate its feasibility, our assay was applied to 40 DNA extracted from sputum samples. The results obtained from H. influenzae real-time MCDA were compared with that of H. influenzae–loop-mediated isothermal amplification (H. influenzae-LAMP) and MCDA-based lateral flow biosensor (MCDA-LFB). The positive rate of the real-time MCDA assay was 62.5%, which was consistent with the H. influenzae-MCDA-LFB assay, but was more sensitive than H. influenzae-LAMP (57.5%). Furthermore, the H. influenzae real-time MCDA assay takes only 40 min, which was less than that of a traditional PCR test. Taken together, the H. influenzae real-time MCDA assay reported here offers a new and valuable diagnostic tool for the reliable and rapid detection of H. influenzae.

The self-interference of an unmanned underwater vehicle (UUV) weakens its ability to detect targets of interest. Due to limitations in the size of the sonar array and the complexity of the interference, the performance of existing self-interference suppression methods in practical applications is unsatisfactory. Our research focuses on analyzing the influence of near-field interferences on the sample covariance matrix (SCM) and proposes an interference suppression algorithm based on an improved autoencoder. The proposed algorithm effectively learns the feature distribution of near-field interferences within the covariance domain and reconstructs the pure signal covariance matrix through the cancellation of the near-field interference features. Moreover, the proposed algorithm can meet the requirements of real-time processing and does not require prior knowledge about the positions or propagation of interference. Simulations demonstrate that the proposed algorithm outperforms comparison methods, particularly in scenarios with low signal-to-interference ratios and a limited number of sensors. Furthermore, lake experiments provide additional evidence of the proposed algorithm’s good performance in practical applications.

Additive manufacturing (AM) was recently developed for building intricate devices in many fields. Especially for laser powder bed fusion (LPBF), its high-precision manufacturing capability and adjustable process parameters are involved in tailoring the performance of functional components. NiTi is well-known as smart material utilized widely in biomedical fields thanks to its unique superelastic and shape-memory performance. However, the properties of NiTi are extremely sensitive to material microstructure, which is mainly determined by process parameters in LPBF. In this work, we choose a unique NiTi intricate component: a robotic cannula tip, in which material superelasticity is a crucial requirement as the optimal object. First, the process window was confirmed by printing thin walls and bulk structures. Then, for optimizing parameters precisely, a Gyroid-type sheet triply periodic minimal-surface (G-TPMS) structure was proposed as the standard test sample. Finally, we verified that when the wall thickness of the G-TPMS structure is smaller than 130 μm, the optimal energy density changes from 167 J/m3 to 140 J/m3 owing to the lower cooling rate of thinner walls. To sum up, this work puts forward a novel process optimization methodology and provides the processing guidelines for intricate NiTi components by LPBF.

Mycoplasma pneumoniae (MP), the causative agent of MP pneumonia (MPP), has posed a substantial burden to public health owing to a lack of rapid and effective diagnostic methods. Here, we designed a loop-mediated isothermal amplification (LAMP)-based assay, termed LAMP, combined with a nanoparticle-based lateral flow biosensor (LAMP-LFB) for rapid and sensitive diagnosis of MP.-LAMP-LFB included a set of six primers targeting the community-acquired respiratory distress syndrome (CARDS) toxin gene and was performed optimally at 63°C for only 30 min. The resulting LAMP products could be visually indicated by LFB within 2 min, thus the whole process could be accomplished within an hour. MP-LAMP-LFB’s sensitivity was 50 fg per reaction, which was in complete accordance with these results obtained from real-time turbidity and visual detection reagent (VDR). MP-LAMP-LFB had no cross-reactivity with other pathogens that had similar clinical presentations. Our assay was further validated using 100 nasopharyngeal swab samples collected from children suspected of MPP, and the result was compared with the real-time PCR method. With a positive rate of 50%, the data indicated that MP-LAMP-LFB is a sensitive test for MP detection in clinical settings. Collectively, the MP-LAMP-LFB assay targeting the CARDS toxin gene was a rapid, highly sensitive, and specific test that could be widely applied in point-of-care settings and basic medical facilities in rural areas.

BackgroundStudies have shown that lymphocyte dysfunction can occur during the early stages of sepsis and that cell dysfunction is associated with mitochondrial dysfunction. Therefore, quantifying the mitochondrial function of lymphocytes in patients with sepsis could be valuable for the early diagnosis of sepsis.MethodsSeventy-nine patients hospitalized from September 2020 to September 2021 with Sepsis-3 were retrospectively analyzed and subsequently compared with those without sepsis.ResultsUnivariate analysis showed statistical differences between the data of the two groups regarding age, neutrophil/lymphocyte, procalcitonin (PCT), C-reactive protein, total bilirubin, serum creatinine, type B natriuretic peptide, albumin, prothrombin time, activated partial thromboplastin time, lactic acid, single-cell mitochondrial mass (SCMM)-CD3, SCMM-CD4, SCMM-CD8, and Acute Physiology and Chronic Health Evaluation II score (P < 0.05). Multivariate logistic regression analysis performed on the indicators mentioned above demonstrated a statistical difference in PCT, lactic acid, SCMM-CD4, and SCMM-CD8 levels between the two groups (P < 0.05). The receiver operating characteristic curves of five models were subsequently compared [area under the curve: 0.740 (PCT) vs. 0.933 (SCMM-CD4) vs. 0.881 (SCMM-CD8) vs. 0.961 (PCT + SCMM-CD4) vs. 0.915 (PCT+SCMM-CD8), P < 0.001].ConclusionSCMM-CD4 was shown to be a better diagnostic biomarker of early sepsis when compared with the traditional biomarker, PCT. Furthermore, the value of the combination of PCT and SCMM-CD4 in the diagnosis of early sepsis was better than that of SCMM-CD4 alone.

Ferroptosis is a new type of iron-dependent programmed cell death. In recent years, its role in the diagnosis and treatment of multiple tumors, including non-small cell lung cancer (NSCLC), has been continuously observed. The relationship between the ferroptosis-related genes and the prognosis of patients with NSCLC needs to be clarified. In this study, The Cancer Genome Atlas (TCGA) and the Gene Expression Synthesis database (Gene Expression Omnibus, GEO) were used to build a model of ferroptosis-related differentially expressed genes (DEGs). A total of 101 ferroptosis-related DEGs were screened using R language, and a 12-gene signature was finally established through univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. According to the risk scores, the patients were divided into a high-risk or a low-risk group, with patients in the low-risk group showing better prognosis. AURKA, one of the genes in the 12-gene signature, was found to be highly expressed in tumors. In addition, further study verified AURKA to be a negative regulator of ferroptosis in NSCLC cells. Ophiopogonin B (OP-B) had been reported to induce apoptosis, mitotic catastrophe, and autophagy in NSCLC cells. Herein, proteomic sequencing analysis and OP-B administration revealed the upregulation of AURKA and the downregulation of PHKG2 and SLC7A5 in the 12-gene signature, indicating that OP-B induced ferroptosis in NSCLC. Determination of the concentrations of malondialdehyde (MDA), glutathione (GSH), and intracellular iron and the mitochondrial membrane potential (MMP) confirmed the induction of ferroptosis by OP-B in vitro. Furthermore, transmission electron microscopy (TEM) examination of lung cancer xenotransplantation in nude mice confirmed that OP-B induced ferroptosis in vivo. Further study of the molecular mechanism showed that the ferroptosis effect caused by OP-B can be partially reversed by the overexpression of AURKA. Overall, our study established a new ferroptosis-related risk prediction model for the prognosis of patients with NSCLC, revealed the enrichment pathways of ferroptosis in NSCLC, and discovered the negative regulation of AURKA in ferroptosis. On this basis, we demonstrated that OP-B can induce ferroptosis in NSCLC and clarified the specific molecular mechanism of OP-B inducing ferroptosis by regulating the expression of AURKA.

BackgroundDespite improved overall survival outcomes, chemotherapy has brought concerns for heart disease–related death (HDRD) among cancer patients. The effect of chemotherapy on the risk of HDRD in anaplastic astrocytoma (AA) patients remains unclear.MethodsWe obtained 7,129 AA patients from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Kaplan–Meier and Cox regression analysis were conducted to evaluate the effect of chemotherapy on the HDRD risk. Based on the competing risk model, we calculated the cumulative incidences of HDRD and non-HDRD and performed univariate and multivariate regression analyses. Then, a 1:1 propensity score matching (PSM) was used to improve the comparability between AA patients with and without chemotherapy. Landmark analysis at 216 and 314 months was employed to minimize immortal time bias.ResultsAA patients with chemotherapy were at a lower HDRD risk compared to those patients without chemotherapy (adjusted HR=0.782, 95%CI=0.736–0.83, P

Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest. They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic factors. Few studies have reported Alzheimer’s disease treatment using dental pulp stem cells. Rat models of Alzheimer’s disease were established by injecting amyloid-β1–42 into the hippocampus. Fourteen days later, 5 × 106 dental pulp stem cells were injected into the hippocampus. Immunohistochemistry and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin, NeuN, and neurofilament 200 in the hippocampus, while the expression of amyloid-β was decreased. Moreover, cognitive and behavioral abilities were improved. These findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins, which indicates a potential therapeutic effect for Alzheimer’s disease. This study was approved by the Animal Ethics Committee of Harbin Medical University, China (approval No. KY2017-132) on February 21, 2017.

Dental pulp stem cells are a type of adult stem cells with strong proliferative ability and multi-differentiation potential. There are no studies on treatment of vascular dementia with dental pulp stem cells. In the present study, rat models of vascular dementia were established by two-vessel occlusion, and 30 days later, rats were injected with 2 × 107 dental pulp stem cells via the tail vein. At 70 days after vascular dementia induction, dental pulp stem cells had migrated to the brain tissue of rat vascular dementia models and differentiated into neuron-like cells. At the same time, doublecortin, neurofilament 200, and NeuN mRNA and protein expression levels in the brain tissue were increased, and glial fibrillary acidic protein mRNA and protein expression levels were decreased. Behavioral testing also revealed that dental pulp stem cell transplantation improved the cognitive function of rat vascular dementia models. These findings suggest that dental pulp stem cell transplantation is effective in treating vascular dementia possibly through a paracrine mechanism. The study was approved by the Animal Ethics Committee of Harbin Medical University (approval No. KY2017-132) in 2017.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations and the pathogenesis of SLE is still unclear. Various omics results have been reported for SLE, but the molecular hallmarks of SLE, especially in patients with different disease activity, using an integrated multi-omics approach have not been fully investigated. Here, we collected blood samples from 10 healthy controls (HCs) and 40 SLE patients with different clinical activity including inactive (IA), low activity (LA), and high activity (HA). Using an integrative analysis of proteomic, metabolomic and lipidomic profiles, we report the multi-omics landscape for SLE. The molecular changes suggest that both the complement system and the inflammatory response were activated in SLEs and were associated with disease activity. Additionally, activation of the immunoglobulin mediated immune response were observed in the LA stage of the disease, however this immune response was suppressed slightly in the HA stage. Finally, an imbalance in lipid metabolism, especially in sphingolipid metabolism, accompanied with dysregulated apolipoproteins were observed to contribute to the disease activity of SLE. The multi-omics data presented in this study and the characterization of peripheral blood from SLE patients may thus help provide important clues regarding the pathogenesis of SLE.

ObjectiveThis study aimed to explore the shared mechanism and candidate drugs of multiple sclerosis (MS) and Sjögren’s syndrome (SS).MethodsMS- and SS-related susceptibility genes and differentially expressed genes (DEGs) were identified by bioinformatics analysis based on genome-wide association studies (GWAS) and transcriptome data from GWAS catalog and Gene Expression Omnibus (GEO) database. Pathway enrichment, Gene Ontology (GO) analysis, and protein–protein interaction analysis for susceptibility genes and DEGs were performed. The drugs targeting common pathways/genes were obtained through Comparative Toxicogenomics Database (CTD), DrugBank database, and Drug–Gene Interaction (DGI) Database. The target genes of approved/investigational drugs for MS and SS were obtained through DrugBank and compared with the common susceptibility genes.ResultsBased on GWAS data, we found 14 hub common susceptibility genes (HLA-DRB1, HLA-DRA, STAT3, JAK1, HLA-B, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRB5, HLA-DPA1, HLA-DPB1, TYK2, IL2RA, and MAPK1), with 8 drugs targeting two or more than two genes, and 28 common susceptibility pathways, with 15 drugs targeting three or more than three pathways. Based on transcriptome data, we found 3 hub common DEGs (STAT1, GATA3, PIK3CA) with 3 drugs and 10 common risk pathways with 435 drugs. “JAK-STAT signaling pathway” was included in common susceptibility pathways and common risk pathways at the same time. There were 133 overlaps including JAK-STAT inhibitors between agents from GWAS and transcriptome data. Besides, we found that IL2RA and HLA-DRB1, identified as hub common susceptibility genes, were the targets of daclizumab and glatiramer that were used for MS, indicating that daclizumab and glatiramer may be therapeutic for SS.ConclusionWe observed the shared mechanism of MS and SS, in which JAK-STAT signaling pathway played a vital role, which may be the genetic and molecular bases of comorbidity of MS with SS. Moreover, JAK-STAT inhibitors were potential therapies for MS and SS, especially for their comorbidity.

Abstract Background Ischaemic stroke has become the main cause of death and severe neurological disorders, for which effective restorative treatments are currently limited. While stem cell transplantation offers therapeutic potential through neural regeneration, this approach is associated with the challenges of limited applicable sources. Hair follicle stem cells (HFSCs) are multipotential cells that can differentiate into ectodermal and mesodermal lineages and proliferate for long periods. The therapeutic potentials of HFSCs have not been investigated in ischaemic stroke models, and therefore, in this study, we aimed to determine whether they could survive and migrate to ischaemic areas after a stroke attack. Methods A rat model of middle cerebral artery ischaemia/reperfusion was established and intravenously administered HFSCs. The potential of HFSCs to migrate and differentiate into neuron-like cells as well as their ability to reduce the infarct size was evaluated. Rat brain tissue samples were collected 2 weeks after cell transplantation and analysed via TTC staining, immunofluorescence and immunohistochemistry methods. The data were statistically analysed and presented as the means ± standard deviations. Results Intravenously administrated rat HFSCs were able to migrate to the penumbra where they expressed neuron-specific markers, reduced the infarct volume and promoted neurological recovery. Conclusion HFSC transplantation has therapeutic potential for ischaemic stroke and is, therefore, worthy of further investigation toward possible clinical development for treating stroke patients.

Bidder collusion in reverse auctions is a pervasive phenomenon that leads to a series of problems for buyers and their supply chains. This work aims to conduct a hazard analysis on a first-price sealed-bid reverse auction with bidder collusion by applying colored timed Petri nets, in which places and transition nodes represent bidding resources and activities. This work successfully dissects the collusion process, quantifies the harm of collusion, and compares the harm levels. The results of the simulation disclose two main causal factors for bidder collusion information asymmetry and strong relationship between strong bidders. This study also identifies the situations where there is a strong relationship between strong bidders. Based on these findings, several recommendations are proposed to reduce the harm of the ring game in a real reverse auction process. Thus, this study helps the buyers to take control of reverse auctions.

Bordetella pertussis is the most frequent causative agent for pertussis, which is a highly contagious disease. Here, we developed a method based on loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor (LFB) for the timely diagnosis of B. pertussis infections. A set of six primers was designed for LAMP reactions, and the LAMP results were rapidly and visually indicated using LFB. The recommended condition for the B. pertussis LAMP reactions is 40 min at 66°C. Our results confirmed that the LAMP-LFB assay could specifically detect B. pertussis and did not cross-react with non-B. pertussis isolates. The sensitivity of the B. pertussis LAMP-LFB assay was 50 fg per reaction. In particular, 108 nasopharyngeal swab (NPS) samples were collected to evaluate the B. pertussis LAMP-LFB assay, and the results were compared with those of the quantitative PCR (qPCR) method. The positive rates of B. pertussis LAMP-LFB and qPCR were 40.7% and 38.8%, respectively, and the agreement between the LAMP-LFB and qPCR results was 98%, with a kappa value of 0.96. The whole process of LAMP-LFB can be completed within 1 h, which is much shorter than that of qPCR, including about 15 min of rapid DNA extraction, 40 min of LAMP reaction, and within 2 min of the LFB test. Collectively, the B. pertussis LAMP-LFB assay developed in this report offers a new option for the rapid, reliable, and simple diagnosis of B. pertussis infections.

Abstract Background Troxerutin (TRX), a naturally occurring flavonoid in various fruits, has been reported to exhibit numerous pharmacological and biological activities in vitro and in vivo. However, the molecular mechanisms underlying TRX as a treatment for disease are poorly understood. Methods Using pharmacophore mapping and inverse docking, a set of potential TRX target proteins that have been associated with multiple forms of diseases was obtained. Bioinformatic analyses were performed using the Enrichr and STRING servers to analyse the related biological processes and protein-protein networks. Furthermore, we investigated the potential protective effect of TRX against lipopolysaccharide-induced acute lung injury (ALI) using a mouse model. Morphological changes in the lungs were assessed using haematoxylin and eosin staining. Inflammatory cytokines, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10 were investigated using ELISA. Activation of MAPK and NF-κB was detected using western blotting. Results Our network pharmacology analysis revealed the existence of multiple TRX-related chemical-target interactions and the related biological processes. We found that pretreatment with TRX protected against histological changes and obviously regulated the inflammatory cell counts and inflammatory cytokine levels in bronchoalveolar lavage fluid. Based on bioinformatic and western blot analyses, TRX may exert a protective effect against ALI by inhibiting MAPK and NF-κB signalling. Conclusions TRX can ameliorate pulmonary injury by inhibiting the MAPK and NF-κB signalling pathways and has a potential protective effect against ALI. This study may be helpful for understanding the mechanisms underlying TRX action and for discovering new drugs from plants for the treatment of ALI.

Pipeline transportation of crude oil has great advantages over traditional oil transmission methods, in terms of economic and environmental protection. The main costs in the oilfield surface system are the fuel costs for heating the crude oil during transportation and the electricity costs for the pumping units. In the northeast of China, where winter temperatures are extremely low and the oil has a high freezing point and high viscosity, higher temperatures, and pressures are required to transport crude oil. With machine learning widely used in many industries and achieving better results, the digital management of oil pipelines has stored a large amount of production and operation data, which has laid the foundation for the research of oil pipeline process calculation using machine learning methods. In this paper, a crude oil pressure drop calculation of an oil pipeline in Northeast China is carried out based on a neural network. For pipeline pressure drop calculation, the back propagation neural network (BP) pressure drop calculation model and particle swarm optimization for back propagation neuron network (PSO-BP) pressure drop calculation model are established. Two models were used to calculate and compare the measured data, and the average absolute error of the PSO-BP model was the smallest, which was 0.015%. Compared with the BP model, the average relative error is reduced by 13.16%. Therefore, The PSO-BP pressure drop calculation model has high accuracy and is of practical significance for predicting pipeline pressure drop.

Xanomeline, a muscarinic acetylcholine receptor agonist, is one of the first compounds that was found to be effective in the treatment of schizophrenics and attenuating behavioral disturbances of patients with Alzheimer’s disease (AD). However, its role in ischemia-induced injury due to oxygen and glucose deprivation (OGD) remains unclear. Primary rat neuronal cells were exposed to OGD and treated with xanomeline. The effects of xanomeline on apoptosis, cell viability, lactate dehydrogenase (LDH) levels, and reactive oxygen species (ROS) were determined using an Annexin V Apoptosis Detection Kit, a non-radioactive cell counting kit-8 (CCK-8) assay, colorimetric LDH cytotoxicity assay kit, and a dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, respectively, and the expressions of Sirtuin 1, haem oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2), poly ADP-ribose polymerase (PARP), and hypoxia-inducible factor α (HIF-1α) as well as the level of phosphorylated kinase B (p-Akt) were determined by Western blotting. Compared with the control, xanomeline pretreatment increased the viability of isolated cortical neurons and decreased the LDH release induced by OGD. Compared with OGD-treated cells, xanomeline inhibited apoptosis, reduced ROS production, attenuated the OGD-induced HIF-1α increase and partially reversed the reduction of HO-1, Sirtuin-1, Bcl-2, PARP, and p-Akt induced by OGD. In conclusion, xanomeline treatment protects cortical neuronal cells possibly through the inhibition of apoptosis after OGD.

Data on particle removal from surfaces is yet to be presented properly. This data is explored and the mathematical models are presented in the previous paper “New model for particle removal from surface in presence of deformed liquid bridge” [1], which predict the fluid velocity required to initiate the motion of a particle. However, the models still need to be verified by the experiment. The experimental data in this paper measured the critical fluid flow velocity when the particles were about to removal from the surface. The particle removal including the process without the effect of liquid bridge and the process with the existence of liquid bridge. Different diameter of the silica particles were used to measured the critical fluid flow velocity without the liquid bridge. In addition, with the existing of the liquid bridge, the same diameter of the silica particles and the ice particles were used to researched the critical state. The data has implications in furthering the understanding of the underlying mechanisms during the removal of particles from surfaces exposed to fluid flow. Keywords: Particle removal, Surface, Liquid bridge, Adhesion

Abstract Background Spinal cord injury (SCI) is one of the most severe central nervous system injuries. Currently, transplanting bone marrow mesenchymal stem cells (BMSCs) is considered a therapeutic option for SCI. Tanshinone IIA (TIIA) is one of the extracts obtained from Salvia miltiorrhiza Bunge, which has been shown to have some protective effects against SCI. The present research was aimed to explore whether TIIA would influence the fate of transplanted BMSCs in a rat model of SCI, especially with regard to their differentiation into neuronal cells. Methods Bone marrow mesenchymal stem cells were obtained from immature rats and identified using flow cytometry. After SCI, 1.0 × 107 cells labeled with PKH67 were transfused into the injured spinal cord. TIIA was first injected into the tail vein (30 mg/kg) 1 h before surgery. From day 1 to day 7 post-SCI, TIIA was injected (20 mg/kg) per day at the same time. Recovery of locomotor function and histological regeneration of the spinal cord were compared among the groups, with the differentiation and distribution of BMSCs determined anatomically and biochemically by the expression of neural cell markers. Results Locomotor assessments showed that the rats in the BMSCs + TIIA group exhibited higher scores (19.33 ± 0.58) than those in the other groups (13.67 ± 1.53, 17.67 ± 0.58, 18.00 ± 1.73). The area of the cavity in the BMSCs + TIIA rats was smaller than that in the other groups (1.30 ± 0.56, 10.39 ± 1.59, 6.84 ± 1.18, 4.36 ± 0.69). Co-expression of glial fibrillary acid protein was observed in transplanted BMSCs, with a reduced rate in the BMSCs + TIIA group relative to that in the SCI group. In contrast, the expression levels of Nestin, neuron-specific nuclear protein (NeuN) and neurofilament protein 200 (NF200) were greatest in the transplanted cells in the BMSCs + TIIA group. Conclusions Tanshinone IIA treatment enhances the therapeutic effects of BMSC transplant on SCI, likely by promoting the differentiation of neuronal cells.

Single-beacon navigation for group autonomous underwater vehicles (AUVs) suffers from long navigation period and asynchronization. This paper addresses the problem by introducing the single-input-multiple-output (SIMO) model, where, a single AUV transmits the signal and other AUVs receive the signal. Utilizing the time-delay of signals from the beacon and the sender, the navigation for all AUVs is achieved simultaneously, and the navigation period is dramatically decreased. Moreover, based on the new SIMO model, a tracking method utilizing extended Kalman filter is also put forward to increase the navigation precision and reduce the computational burden. Finally, a coordinate fusion algorithm based on the location, error, and time-delay is presented, which fuses the independent AUV coordinates to be a higher precision holistic coordinate system for group AUVs. Simulation results show the effectiveness of the proposed method.

Background/Aims: Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. Methods: The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Results: Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. Conclusions: These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future.

Although several optimal mycobacterial interspersed repetitive units–variable number tandem repeat (MIRU–VNTR) loci have been suggested for genotyping homogenous Mycobacterium tuberculosis, including the Beijing genotype, a more efficient and convenient selection strategy for identifying optimal VNTR loci is needed. Here 281 M. tuberculosis isolates were analyzed. Beijing genotype and non-Beijing genotypes were identified, as well as Beijing sublineages, according to single nucleotide polymorphisms. A total of 22 MIRU–VNTR loci were used for genotyping. To efficiently select optimal MIRU–VNTR loci, we established accumulations of percentage differences (APDs) between the strains among the different genotypes. In addition, we constructed a minimum spanning tree for clustering analysis of the VNTR profiles. Our findings showed that eight MIRU–VNTR loci displayed disparities in h values of ≥0.2 between the Beijing genotype and non-Beijing genotype isolates. To efficiently discriminate Beijing and non-Beijing genotypes, an optimal VNTR set was established by adding loci with APDs ranging from 87.2% to 58.8%, resulting in the construction of a nine-locus set. We also found that QUB11a is a powerful locus for separating ST10s (including ST10, STF and STCH1) and ST22s (including ST22 and ST8) strains, whereas a combination of QUB11a, QUB4156, QUB18, Mtub21 and QUB26 could efficiently discriminate Beijing sublineages. Our findings suggested that two nine-locus sets were not only efficient for distinguishing the Beijing genotype from non-Beijing genotype strains, but were also suitable for sublineage genotyping with different discriminatory powers. These results indicate that APD represents a quantitative and efficient approach for selecting MIRU–VNTR loci to discriminate between divergent M. tuberculosis sublineages.Emerging Microbes & Infections (2017) 6, e68; doi:10.1038/emi.2017.58; published online 26 July 2017

Microvascular and macrovascular complications are major causes of disability and death in diabetic patients. High levels of blood glucose sabotage the integrity of blood vessels and induce endothelial dysfunction. Fenofibrate is an agonist of peroxisome proliferator-activated receptor α and can reduce the incidence of cardiovascular events in diabetic patients. This study tested the hypothesis that fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction via activating endothelial nitric oxide synthase (eNOS) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A streptozotocin (STZ)-induced diabetic model was established by intraperitoneal injection of STZ (dissolved in sodium citrate buffer) at a dose of 60 mg/kg for 5 consecutive days. Mice were administered fenofibrate (100 mg/kg/d, i.g.) for 14 days. The endothelial function of extracted mouse aortae was examined by evaluating acetylcholine induced endothelium-dependent relaxation combined with phenylephrine-induced vasoconstriction and sodium nitroprusside-induced endothelium-independent relaxation. Superoxide onion (O2−) was determined using dihydroethidium staining of aortae. Functions of mouse aortic endothelial cells (MAECs) were assessed, and expression levels of eNOS and AMPK were determined by Western blotting. Fenofibrate ameliorated the impaired endothelium-dependent relaxation in diabetic mice and decreased the level of intracellular O2- in diabetic mouse aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, increased nitric oxide production, and decreased the O2- level, as well as activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction, which was possibly related to the activation of eNOS and AMPK phosphorylation.