The importance of micro-electromechanical systems (MEMS) for radio-frequency (RF) applications is rapidly growing. In RF mobile-communication systems, MEMS-based circuits enable a compact implementation, low power consumption and high RF performance, e.g., bulk-acoustic wave filters with low insertion loss and low noise or fast and reliable MEMS switches. However, the cross-hierarchical modelling of micro-electronic and micro-electromechanical constituents together in one multi-physical design process is still not as established as the design of integrated micro-electronic circuits, such as operational amplifiers. To close the gap between micro-electronics and micro-electromechanics, this paper presents an analytical approach towards the linear top-down design of MEMS resonators, based on their electrical specification, by the solution of the mechanical wave equation. In view of the central importance of thermal effects for the performance and stability of MEMS-based RF circuits, the temperature dependence was included in the model; the aim was to study the variations of the RF parameters of the resonators and to enable a temperature dependent MEMS oscillator simulation. The variations of the resonator parameters with respect to the ambient temperature were then verified by RF measurements in a vacuum chamber at temperatures between −35 ∘C and 85 ∘C. The systematic body of data revealed temperature coefficients of the resonant frequency between −26 ppm/K and −20 ppm/K, which are in good agreement with other data from the literature. Based on the MEMS resonator model derived, a MEMS oscillator was designed, simulated, and measured in a vacuum chamber yielding a measured temperature coefficient of the oscillation frequency of −26.3 ppm/K. The difference of the temperature coefficients of frequency of oscillator and resonator turned out to be mainly influenced by the limited Q-factor of the MEMS device. In both studies, the analytical model and the measurement showed very good agreement in terms of temperature dependence and the prediction of fabrication results of the resonators designed. This analytical modelling approach serves therefore as an important step towards the design and simulation of micro-electronics and micro-electromechanics in one uniform design process. Furthermore, temperature dependences of MEMS oscillators can now be studied by simulations instead of time-consuming and complex measurements.

In this study, the antifungal activity of yellow mustard (YMF) and oriental mustard (OMF) meal extracts against 14 strains of fungi was tested on a solid medium. The results obtained with the YMF were next confirmed in liquid medium determining the minimum inhibitory concentration (MIC) and the minimum fungicide concentration (MFC). Finally, the use of YMF as a natural preservative to extend the useful life of bread was evaluated. Breads with different concentrations of YMF (2, 4, 6 and 8 g/kg) were prepared and contaminated with Aspergillus flavus ISPA 8111 and Penicilliumnordicum CECT 2320. For 10 days the formation of mycelium was observed, and after that the fungal growth and the mycotoxins production was determined. The results obtained with the YMF were compared with breads treated with the commercial additive sodium propionate (E-281). The results showed a significant reduction of the fungal population using 6 g/kg and 8 g/kg of YMF in bread contaminated with A. flavus and with P.nordicum and an extensions of the breads shelf life of 7 and 5 days, respectively, in comparison with the control experiment. A reduction of 78% of AFB₁ was observed using 6 g/kg of YMF while no AFB1 production was detected employing 8 g/kg of YMF in bread preparation.

A current challenge is to develop tags to precisely visualize proteins in cells by light and electron microscopy. Here, we introduce FerriTag, a genetically-encoded chemically-inducible tag for correlative light-electron microscopy. FerriTag is a fluorescent recombinant electron-dense ferritin particle that can be attached to a protein-of-interest using rapamycin-induced heterodimerization. We demonstrate the utility of FerriTag for correlative light-electron microscopy by labeling proteins associated with various intracellular structures including mitochondria, plasma membrane, and clathrin-coated pits and vesicles. FerriTagging has a good signal-to-noise ratio and a labeling resolution of approximately 10 nm. We demonstrate how FerriTagging allows nanoscale mapping of protein location relative to a subcellular structure, and use it to detail the distribution and conformation of huntingtin-interacting protein 1 related (HIP1R) in and around clathrin-coated pits.

Tumor-derived soluble factors promote the production of Gr-1+CD11b+ immature myeloid cells, and TGFβ signaling is critical in their immune suppressive function. Here, we report that miR-130a and miR-145 directly target TGFβ receptor II (TβRII) and are down-regulated in these myeloid cells, leading to increased TβRII. Ectopic expression of miR-130a and miR-145 in the myeloid cells decreased tumor metastasis. This is mediated through a downregulation of type 2 cytokines in myeloid cells and an increase in IFNγ-producing cytotoxic CD8 T lymphocytes. miR-130a- and miR-145-targeted molecular networks including TGFβ and IGF1R pathways were correlated with higher tumor stages in cancer patients. Lastly, miR-130a and miR-145 mimics, as well as IGF1R inhibitor NT157 improved anti-tumor immunity and inhibited metastasis in preclinical mouse models. These results demonstrated that miR-130a and miR-145 can reprogram tumor-associated myeloid cells by altering the cytokine milieu and metastatic microenvironment, thus enhancing host antitumor immunity.

The DNA damage sensor XPC is involved in nucleotide excision repair. Here we show that in the absence of damage, XPC co-localizes with RNA polymerase II (Pol II) and active post-translational histone modifications marks on a subset of class II promoters in human fibroblasts. XPC depletion triggers specific gene down-expression due to a drop in the deposition of histone H3K9 acetylation mark and pre-initiation complex formation. XPC interacts with the histone acetyltransferase KAT2A and specifically triggers the recruitment of the KAT2A-containing ATAC complex to the promoters of down-expressed genes. We show that a strong E2F1 signature characterizes the XPC/KAT2A-bound promoters and that XPC interacts with E2F1 and promotes its binding to its DNA element. Our data reveal that the DNA repair factor XPC is also an RNA polymerase II cofactor recruiting the ATAC coactivator complex to promoters by interacting with the DNA binding transcription factor E2F1.

A previously reported gene cluster encoding four nisin-like peptides, three with the same sequence (NsoA1-3) and the unique NsoA4, produced antimicrobial activity in the presence of trypsin after heterologous expression in Lactococcus lactis. Protein extracts were separated by SDS gel electrophoresis or immunoprecipitation using an antibody to the NsoA2 leader. Tryptic peptides observed by LC-MS/MS covered the complete sequence of preNsoA1-3 and part of the leader sequence of preNsoA4 and confirmed the expression and the predicted sequences of the preNsoA peptides. Further, the data revealed that the preNsoA1-3 peptides were partly modified with dehydrations and formation of lanthionine rings. A certain amount of fully modified preNsoA1-3 was observed. Details of modifications of the core peptide and the C-terminal tryptic peptide TATCGCHITGK covering rings D and E indicated that 22% of these preNsoA1-3 peptides were completely modified. A lower amount of ring formation is estimated for rings A-C. Intact masses of immunoprecipitation-derived peptides determined by LC-MS accurately matched the expected preNsoA precursor peptides. The most abundant peptides detected were preNsoA2-3-8H2O followed by preNsoA1-8H2O and other states of dehydration. The results confirm incomplete processing of preNsoA peptides in the heterologous system, with the formation of a certain amount of fully modified peptides.

Population mobility has been demonstrated to contribute to the persistent transmission and global diffusion of epidemics. In the Pacific Islands, population mobility is particularly important for emerging infectious diseases, disease elimination programs, and diseases spread by close contact. The extent of population mobility between American Samoa villages, Samoa districts and other countries was investigated based on travel data collected during community surveys in American Samoa in 2010 and 2014. Within American Samoa, workers commuted daily across the whole of the main island of Tutuila, with work hubs drawing from villages across the island. Of the 670 adult workers surveyed, 37% had traveled overseas in the past year, with 68% of trips to Samoa. Of children aged 8-13 years (n = 337), 57% had traveled overseas, with 55% of trips to Samoa. An extensive network of connections between American Samoa villages and Samoa districts was demonstrated, with most trips lasting one week to one month. Our study showed that populations in the Samoan islands are highly mobile, and quantified the extent and destinations of their travels. Our findings offer insight into the impact of population mobility on the transmission of infectious diseases and data to refine existing models of disease transmission in the Pacific islands.

Escherichia coli and Staphylococcus aureus bacterial retention on mirror-polished and ultrashort pulse laser-textured surfaces is quantified with a new approach based on ISO standards for measurement of antibacterial performance. It is shown that both wettability and surface morphology influence antibacterial behavior, with neither superhydrophobicity nor low surface roughness alone sufficient for reducing initial retention of either tested cell type. Surface structures comprising spikes, laser-induced periodic surface structures (LIPSS) and nano-pillars are produced with 1030 nm wavelength 350 fs laser pulses of energy 19.1 μJ, 1.01 μJ and 1.46 μJ, respectively. SEM analysis, optical profilometry, shear force microscopy and wettability analysis reveal surface structures with peak separations of 20-40 μm, 0.5-0.9 μm and 0.8-1.3 μm, average areal surface roughness of 8.6 μm, 90 nm and 60 nm and static water contact angles of 160°, 119° and 140°, respectively. E. coli retention is highest for mirror-polished specimens and spikes whose characteristic dimensions are much larger than the cell size. S. aureus retention is instead found to be inhibited under the same conditions due to low surface roughness for mirror-polished samples (Sa: 30 nm) and low wettability for spikes. LIPSS and nano-pillars are found to reduce E. coli retention by 99.8% and 99.2%, respectively, and S. aureus retention by 84.7% and 79.9% in terms of viable colony forming units after two hours of immersion in bacterial broth due to both low wettability and fine surface features that limit the number of available attachment points. The ability to tailor both wettability and surface morphology via ultrashort pulsed laser processing confirms this approach as an important tool for producing the next generation of antibacterial surfaces.

Graphene oxide (GO) modulates the functions of antigen-presenting cells including dendritic cells (DCs). Although carbon nanotubes affect expression of the MHC class I-like CD1d molecule, whether GO can influence immune responses of CD1d-dependent invariant natural killer T (iNKT) cells remains unclear. Here, we investigated the impact of GO on inflammatory responses mediated by α-galactosylceramide (α-GalCer), an iNKT cell agonist. We found that in vivo GO treatment substantially inhibited the capacity of α-GalCer to induce the iNKT cell-mediated trans-activation of and cytokine production by innate and innate-like cells, including DCs, macrophages, NK cells, and γδ T cells. Such effects of GO on α-GalCer-induced inflammatory responses closely correlated with iNKT cell polarization towards TGFβ production, which also explains the capacity of GO to expand regulatory T cells. Interestingly, the absence of TLR4, a receptor for GO, failed to downregulate, and instead partially enhanced the anti-inflammatory activity of GO against α-GalCer-elicited responses, implying negative effects of TLR4 signaling on the anti-inflammatory properties of GO. By employing an α-GalCer-induced sepsis model, we further demonstrated that GO treatment significantly protected mice from α-GalCer-induced lethality. Taken together, we provide strong evidence that GO holds promise as an adjuvant to modulate iNKT cell responses for immunotherapy.

MicroRNAs (miRNAs) have been explored in many critical cellular processes, including proliferation and apoptosis. The purpose of this study was to detect the biological function and regulation of miR-99b-5p and miR-203a-3p in gastric cancer (GC). Here, we demonstrated that miR-99b-5p/203a-3p were downregulated in both GC tissues and cell lines. MiR-99b-5p/203a-3p overexpression reduced GC cell proliferation and cell cycle progression in vitro. Notably, we combined bioinformatics tools with biological validation assays to demonstrate that insulin-like growth factor 1 receptor (IGF-1R) is a direct co-target and functional mediator of miR-99b-5p/203a-3p in GC cells. Mechanistically, the AKT pathway, which is downstream of IGF-1R, is essential for the functional roles of miR-99b-5p/203a-3p in GC cells. Taken together, our data revealed that IGF-1R is a direct co-target of miR-99b-5p/203a-3p, and miR-99b-5p/203a-3p may function as tumor suppressive miRNAs by negatively regulating IGF-1R expression in GC cells.

The diversity and basic functional attributes of the gut microbiome of healthy Indians is not well understood. This study investigated the gut microbiome of three Indian communities: individuals residing in rural and urban (n = 49) sea level Ballabhgarh areas and in rural high altitude areas of Leh, Ladakh in North India (n = 35). Our study revealed that the gut microbiome of Indian communities is dominated by Firmicutes followed by Bacteroidetes, Actinobateria and Proteobacteria. Although, 54 core bacterial genera were detected across the three distinct communities, the gut bacterial composition displayed specific signatures and was observed to be influenced by the topographical location and dietary intake of the individuals. The gut microbiome of individuals living in Leh was observed to be significantly similar with a high representation of Bacteroidetes and low abundance of Proteobacteria. In contrast, the gut microbiome of individuals living in Ballabhgarh areas harbored higher number of Firmicutes and Proteobacteria and is enriched with microbial xenobiotic degradation pathways. The rural community residing in sea level Ballabhgarh areas has unique microbiome characterized not only by a higher diversity, but also a higher degree of interindividual homogeneity.

We determined the effects of different expression levels of arrestin-1-3A mutant with enhanced binding to light-activated rhodopsin that is independent of phosphorylation. To this end, transgenic mice that express mutant rhodopsin with zero, one, or two phosphorylation sites, instead of six in the WT mouse rhodopsin, and normal complement of WT arrestin-1, were bred with mice expressing enhanced phosphorylation-independent arrestin-1-3A mutant. The resulting lines were characterized by retinal histology (thickness of the outer nuclear layer, reflecting the number of rod photoreceptors, and the length of the outer segments, which reflects rod health), as well as single- and double-flash ERG to determine the functionality of rods and the rate of photoresponse recovery. The effect of co-expression of enhanced arrestin-1-3A mutant with WT arrestin-1 in these lines depended on its level: higher (240% of WT) expression reduced the thickness of ONL and the length of OS, whereas lower (50% of WT) expression was harmless in the retinas expressing rhodopsin with zero or one phosphorylation site, and improved photoreceptor morphology in animals expressing rhodopsin with two phosphorylation sites. Neither expression level increased the amplitude of the a- and b-wave of the photoresponse in any of the lines. However, high expression of enhanced arrestin-1-3A mutant facilitated photoresponse recovery 2-3-fold, whereas lower level was ineffective. Thus, in the presence of normal complement of WT arrestin-1 only supra-physiological expression of enhanced mutant is sufficient to compensate for the defects of rhodopsin phosphorylation.

Clinical and experimental data suggest that fronto-cortical GABAergic deficits contribute to the pathophysiology of major depressive disorder (MDD). To further test this hypothesis, we used a well characterized rat model for depression and examined the effect of stress on GABAergic neuron numbers and GABA-mediated synaptic transmission in the medial prefrontal cortex (mPFC) of rats. Adult male Wistar rats were subjected to 9-weeks of chronic mild stress (CMS) and based on their hedonic-anhedonic behavior they were behaviorally phenotyped as being stress-susceptible (anhedonic) or stress-resilient. Post mortem quantitative histopathology was used to examine the effect of stress on parvalbumin (PV)-, calretinin- (CR), calbindin- (CB), cholecystokinin- (CCK), somatostatin-(SST) and neuropeptide Y-positive (NPY+) GABAergic neuron numbers in all cortical subareas of the mPFC (anterior cingulate (Cg1), prelimbic (PrL) and infralimbic (IL) cortexes). In vitro, whole-cell patch-clamp recordings from layer II-III pyramidal neurons of the ventral mPFC was used to examine GABAergic neurotransmission. The cognitive performance of the animals was assessed in a hippocampal-prefrontal-cortical circuit dependent learning task. Stress exposure reduced the number of CCK-, CR- and PV-positive GABAergic neurons in the mPFC, most prominently in the IL cortex. Interestingly, in the stress-resilient animals, we found higher number of neuropeptide Y-positive neurons in the entire mPFC. The electrophysiological analysis revealed reduced frequencies of spontaneous and miniature IPSCs in the anhedonic rats and decreased release probability of perisomatic-targeting GABAergic synapses and alterations in GABAB receptor mediated signaling. In turn, pyramidal neurons showed higher excitability. Anhedonic rats were also significantly impaired in the object-place paired-associate learning task. These data demonstrate that long-term stress results in functional and structural deficits of prefrontal GABAergic networks. Our findings support the concept that fronto-limbic GABAergic dysfunctions may contribute to emotional and cognitive symptoms of MDD.

Introduction:Amomum villosum Lour., a herbaceous plant in the ginger family, has been proven to be effective in treating gastrointestinal diseases. It has been listed in the Chinese Pharmacopeia as a legal source of Amomi Fructus. In our previous study, we demonstrated that treatment with extracts of A. villosum prevented the development and progression of intestinal mucositis. In the current study, we aimed to verify and explain the potential beneficial effects of A. villosum on inflammatory bowel disease (IBD). Methods: The effect of water extracts (WEAV) and volatile oil of A. villosum (VOAV) were evaluated on the immunological role of T lymphocytes and intestinal microecology in IBD rats induced with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Body weight, food intake, colon length/weight, and disease activity index (DAI) as well as tissue damage scores were evaluated. The inflammatory response to IBD was assessed by measuring the expression of myeloperoxidase, interleukin (IL)-17 (IL-17), interferon-γ (IFN-γ), IL-10, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). The percentage of regulatory CD4+ T cells in rat spleen was measured by flow cytometry and effects on the microbial community were evaluated by 16S rDNA gene sequencing. Results: All TNBS-induced rats showed typical clinical manifestations of IBD. IBD rats in the WEAV and VOAV treatment groups were effective in relieving body weight and appetite loss. Middle and high dosage of VOAV and WEAV significantly reduced the DAI, and tissue damage scores, whereas colon weight/length ratio was increase. All rats in the WEAV and VOAV groups showed significantly decreased IFN-γ levels and increased levels of IL-10 and TGF-β. Moreover, we observed that the percentage of regulatory CD4+ T cells was significantly enhanced during treatment with WEAV. In addition, administration of WEAV and VOAV effectively inhibited the release of enterogenic endotoxin, increased short-chain fatty acid-producing bacteria belonging to Firmicutes and Bacteroidetes, and decreased the abundance of Proteobacteria. Conclusion: Treatment with WEAV and VOAV significantly attenuated intestinal inflammation in IBD rats, which was possibly associated with its regulation on inflammatory cytokine and CD4+CD25+FOXP3+ T cells. Moreover, WEAV and VOAV may help maintaining the balance of intestinal microecology.

Acetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-induced hepatotoxicity, as well as the putative mechanisms involved. Mice were treated with 4-HPA (6, 12, or 25 mg/kg) for 3 days, 1 h after the last administration of 4-HPA, a single dose of APAP was intraperitoneally infused for mice. APAP caused a remarkable increase of oxidative stress markers, peroxynitrite formation, and fewer activated phase II enzymes. 4-HPA increased Nrf2 translocation to the nucleus and enhanced the activity of phase II and antioxidant enzymes, and could thereby ameliorate APAP-induced liver injury. Studies reveal that 4-HPA, as an active area of bioactive dietary constituents, could protect the liver against APAP-induced injury, implying that 4-HPA could be a new promising strategy and natural hepatoprotective drug.

Salvianolic acid B (SalB) and ginsenoside Re (Re) protect endotheliocytes against apoptosis through different mechanisms. However, whether both compounds could synergistically protect endothelial cells against oxidized low-density lipoprotein (Ox-LDL)-induced apoptosis is unclear. This study aimed to assess the protective effect of combined SalB and Re (SR) treatment on Ox-LDL-induced endothelial apoptosis and to explore the mechanism underlying this effect. Results showed that SalB, Re, or SR could protect against Ox-LDL-induced endothelial apoptosis. Furthermore, the composition of SR was optimized through central composite design with response surface methodology. SR with a composition of 60 μg/mL of SalB and 120 μg/mL of Re exerted the optimal protective effect. Network pharmacology research revealed that SalB and Re in SR synergistically protect against Ox-LDL-induced endothelial apoptosis by regulating oxidative stress and phlogistic pathways. In vitro experiments confirmed these results. Compared with the same dose of SalB or Re alone, SR significantly decreased the contents of inflammatory mediators and increased the activities of antioxidant enzymes. SR could synergistically restore the balanced redox state of the cells and inhibit the activation of nuclear transcription factor kappa B and the caspase cascade by activating the phosphatidylinositol 3 kinase/protein kinase B pathway and inhibiting the phosphorylation of p38 mitogen-activated protein kinase. These pathways are regulated by down-regulating the expression of lectin-like Ox-LDL receptor-1 and NADPH oxidase and up-regulating the expression of estrogen receptor alpha. Therefore, SR effectively prevents Ox-LDL-induced endothelial apoptosis through antioxidative and antiinflammatory mechanisms.

Background: The central goal of palliative care is to optimize the quality of life of patients suffering from life-limiting illnesses, which includes psychosocial and spiritual wellbeing. Research has demonstrated positive correlations between humor and laughter with life satisfaction and other aspects of wellbeing, and physiological symptoms can be improved by humorous stimuli. Objectives: The aim of this review is to evaluate humor interventions and assessments that have been applied in palliative care and to derive implications for future research. Methods: A systematic review of four databases identified 13 included studies. Criteria for inclusion were peer-reviewed English-language studies on humor interventions or assessments in a palliative care context. Results: Two studies on humor interventions and 11 studies on humor assessment were included in the systematic review. Most of these studies were about the patients' perspective on humor in palliative care. Findings showed that humor had a positive effect on patients, their relatives, and professional caregivers. Humor was widely perceived as appropriate and seen as beneficial to care in all studies. Conclusions: Even though humor interventions seem to be potentially useful in palliative care, descriptions evaluating their use are scarce. Overall, research on humor assessment and interventions in palliative care has remained limited in terms of quantity and quality. More research activities are needed to build a solid empirical foundation for implementing humor and laughter as part of regular palliative care activities.

Previous studies have demonstrated that mindfulness practice can improve general cognitive control. However, little research has examined whether mindfulness practices affect different cognitive control strategies. According to the dual mechanisms of control (DMC) model, different cognitive control strategies may play distinct roles in individuals' lives. Proactive control allows people to maintain and prepare for goals, whereas reactive control allows them to respond flexibly to a changing environment. Thus, this study investigates the influences of mindfulness training on proactive and reactive control measured by the AX version of the Continuous Performance Test (AX-CPT). Thirty participants completed AX-CPT and the Five Facet Mindfulness Questionnaire (FFMQ) before and after random assignment to either an 8-week mindfulness training group or a control group. The results showed no interaction between group and test time for AY or BX trial type, but the training group had fewer post-test errors on the BX trial and a higher Behavior Shift Index (BSI) of reaction time (RT) compared with the control group. This finding indicates enhanced trend of proactive control with mindfulness training. A positive correlation between the BSI of RT and observing scores on the FFMQ confirmed the connection between attentional components in mindfulness and proactive control. Errors on the AY trial in the post-test decreased in both groups, reflecting reactive control that did not differ between groups. The 8-week mindfulness training demonstrates a potential improvement effect on proactive control and could be helpful in overcoming interference.

Repeated mild blast-induced traumatic brain injury (rmbTBI), caused by recurrent exposure to low levels of explosive blast, is a significant concern for military health systems. However, the pathobiology of rmbTBI is currently poorly understood. Animal models are important tools to identify the molecular changes of rmbTBI, but comparisons across different models can present their own challenges. In this study, we compared two well-established rodent models of mbTBI, the "KI model" and the "USU/WRAIR model." These two models create different pulse forms, in terms of peak pressure and duration. Following single and double exposures to mild levels of blast, we used in situ hybridization (ISH) to assess changes in mRNA levels of tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH2), and galanin in the locus coeruleus (LC) and dorsal raphe nucleus (DRN). These systems and their transmitters are known to mediate responses to stress and anxiety. We found increased mRNA levels of TH, TPH2 and galanin in the LC and DRN of single-exposed rats relative to sham rats in the KI but not the USU/WRAIR model. Sham mRNA values measured in the USU/WRAIR model were substantially higher than their KI counterparts. Double exposure caused similarly significant increases in mRNA values in the KI model but not the USU/WRAIR model, except TPH2 and galanin levels in the DRN. We detected no cumulative effect of injury in either model at the used inter-injury interval (30 min), and there were no detectable neuropathological changes in any experimental group at 1 day post-injury. The apparent lack of early response to injury as compared to sham in the USU/WRAIR model is likely caused by stressors (e.g., transportation and noise), associated with the experimental execution, that were absent in the KI model. This study is the first to directly compare two established rodent models of rmbTBI, and to highlight the challenges of comparing findings from different animal models. Additional studies are needed to understand the role of stress, dissect the effects of psychological and physical injuries and to identify the window of increased cerebral vulnerability, i.e., the inter-injury interval that results in a cumulative effect following repeated blast exposure.

At present, tuberculosis remains a serious threat to human health. The diagnosis of pulmonary tuberculosis (PTB) is still difficult, and the prominent challenge for diagnosis is the lack of a highly sensitive and specific method. In order to explore the diagnostic value of parallel tests, this study prospectively enrolled 258 patients with smear-negative PTB from May 2, 2015 to December 31, 2016. The sputum specimens and bronchial alveolar lavage fluid (BALF) samples from all patients were assessed for MTB detection by culture, Xpert MTB/RIF, and simultaneous amplification and testing method for TB (SAT-TB). Overall, the sensitivity of any single test using culture, Xpert MTB/RIF, or SAT-TB was lower than that for parallel tests (p < 0.05), and the sensitivity rates for MTB detection in BALF were significantly higher than those in sputum samples. There were lower agreements in the detection results between sputum samples and BALF for all tests (p < 0.05). The parallel tests models of using culture plus Xpert MTB/RIF plus SAT-TB, culture plus Xpert, or culture plus SAT-TB achieved higher sensitivities compared with all three single test models (p < 0.05). Additionally, joint detection using sputum and BALF samples achieved a high sensitivity (0.8566, 95% CI: 0.8086-0.8941). In conclusion, the parallel tests model using culture, Xpert MTB/RIF, and SAT-TB in sputum plus BALF significantly increases the diagnostic performance of smear-negative PTB; thus, this method should be applied clinically when PTB is suspected but smear results are negative.