Nanopore sequencing for smear-negative pulmonary tuberculosis-a multicentre prospective study in China.

PURPOSE: In this prospective study, the diagnosis accuracy of nanopore sequencing-based Mycobacterium tuberculosis (MTB) detection was determined through examining bronchoalveolar lavage fluid (BALF) samples from pulmonary tuberculosis (PTB) -suspected patients. Compared the diagnostic performance of nanopore sequencing, mycobacterial growth indicator tube (MGIT) culture and Xpert MTB/rifampin resistance (MTB/RIF) assays. METHODS: Specimens collected from suspected PTB cases across China from September 2021 to April 2022 were tested then assay diagnostic accuracy rates were compared. RESULTS: Among the 111 suspected PTB cases that were ultimately diagnosed as PTB, the diagnostic rate of nanopore sequencing was statistically significant different from other assays (P < 0.05). Fleiss' kappa values of 0.219 and 0.303 indicated fair consistency levels between MTB detection results obtained using nanopore sequencing versus other assays, respectively. Respective PTB diagnostic sensitivity rates of MGIT culture, Xpert MTB/RIF and nanopore sequencing of 36.11%, 40.28% and 83.33% indicated superior sensitivity of nanopore sequencing. Analysis of area under the curve (AUC), Youden's index and accuracy values and the negative predictive value (NPV) indicated superior MTB detection performance for nanopore sequencing (with Xpert MTB/RIF ranking second), while the PTB diagnostic accuracy rate of nanopore sequencing exceeded corresponding rates of the other methods. CONCLUSIONS: In comparison with MGIT culture and Xpert MTB/RIF assays, BALF's nanopore sequencing provided superior MTB detection sensitivity and thus is suitable for testing of sputum-scarce suspected PTB cases. However, negative results obtained using these assays should be confirmed based on additional evidence before ruling out a PTB diagnosis.

Simultaneous measurement of thermal conductivity and thermal diffusivity of individual microwires by using a cross-wire geometry.

The thermal conductivity and thermal diffusivity of both metallic and non-metallic microwires are simultaneously measured by a cross-wire geometry. In this method, the heating wire serves both as a thermometer and a heater. The deflection of the heating wire is in situ modified by using the Ampère force to contact and separate the test wire. By using the quasi-steady-state measurement, the thermal contact resistances under different contact conditions are obtained so that the effect on thermal conductivity can be eliminated. This method is verified by both the metallic wires and carbon fiber to clarify the effect of the surface radiation heat loss of the test wire. The obtained thermal properties are repeatable though the magnitude of the thermal contact resistance under different contact conditions changes significantly. The cross-wire geometry overcomes the obstacle introduced by different thermal interfacial materials, which provides an accurate and convenient way to measure the thermal properties of microwires.

Integrated Evaluation Method of the Health-Related Physical Environment in Urbanizing Areas: A Case Study From a University Campus in China.

Environmental deterioration in urbanizing areas increases the risks of sudden death as well as chronic, infectious, and psychological diseases. Quantifying health-related physical environment can assess the health risk of urban residents. This study uses an integrated evaluation method to simulate the health-related physical environment in the four dimensions of acoustic, wind, thermal, and landscape. According to the case study of one university campus in an urbanizing area in China, results show that (1) areas with unqualified equivalent A sound levels are generally the sports area, green square 1 and laboratory areas, and residents who stay in these areas for a long time suffer the risks of hearing loss and mental stress. (2) The windless area ratio of teaching area 1 and dormitory area 4 is larger than 20%, and respiratory health risks increase because these areas relate to relatively wind discomfort. (3) The high-temperature zone ratio of sports area and green square 2 is larger than 50%, and heatstroke risks increase since these areas relate with low thermal comfort. (4) The overall landscape perception level of dormitories and dining areas is lower than that of the teaching area, and it can cause anxiety and irritability. (5) The sports area has the lowest average overall score of the health-related physical environment among all functional areas, followed by laboratory areas. These findings indicate that the proposed model and method can be valuable tools for the pre-evaluation and optimization of urban planning. It can reduce the health risks of residents in urbanizing areas and can benefit residents' health and urban sustainable development.

circ_103809 promotes breast cancer progression by regulating the PI3K/AKT signaling pathway.

Breast cancer is one of the most common cancer types in the world. This study was carried out to investigate the functional role of circular RNA circ_103809 in breast cancer. The expression of hsa_circ_103809 in breast cancer tissues and breast cancer cells were verified. After transfection, the expression of hsa_circ_103809 in the cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) and colony formation assay were used to detect cell proliferation. Apoptosis and cell cycle were detected by flow cytometry. AKT, p-AKT, BCL2 and Bax were detected by western blotting. Tumor formation assay was employd in vivo. The expression of circ_103809 in breast cancer was overexpressed. circ_103809 was proved to promote cell proliferation in breast cancer progression. In addition, circ_103809 was also involved in repressing cell apoptosis and accelerating cell cycle progression in vitro. circ_103809 accelerated breast cancer progression via regulating PI3K/AKT signaling. circ_103809 promoted tumor formation in vivo. The circular RNA hsa_circ_103809 was highly expressed in breast cancer tissues and cells, and may play an oncogene role in the development of breast cancer, and is expected to become a new target for breast cancer therapy.

Long-chain non-coding RNA GACAT1 promotes development and progression of breast cancer by targeting microRNA-875-3p.

Role of long-chain non-coding ribonucleic acid (lncRNA) GACAT1 in the development of breast cancer and its possible mechanism were investigated. The levels of GACAT1, microRNA-875-3p and Stonin2 (STON2) in breast cancer tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The level of GACAT1 in breast cancer cell lines was further explored. The effects of GACAT1 and microRNA-875-3p on cell proliferation and cycle were detected by cell counting kit-8 (CCK-8) and flow cytometry. The binding relationship between microRNA-875-3p and STON2, microRNA-875-3p and GACAT1 was examined by a dual luciferase reporting assay. It was confirmed by rescue experiments whether GACAT1 canregulate the level of STON2 by binding to microRNA-875-3p. GACAT1 level was clearly enhanced in breast cancer tissues compared to that of the adjacent tissues. Similar result was observed in breast cancer cell lines. Upregulation of GACAT1 promoted the proliferation and cycle of breast cancer cells including MCF-7 and BCap-37. The dual luciferase reporting assay results indicated that GACAT1 had a binding relationship with microRNA-875-3p. Further experiments confirmed that microRNA-875-3p was conspicuously downregulated in breast cancer tissues, and upregulation of microRNA-875-3p could inhibit the proliferation ability of MCF-7 and BCap-37 cells, and partially reversed the promoting effect of GACAT1 on cell cycle. Through bioinformatics prediction and dual luciferase reporter gene experiments, we found that STON2 might be a target gene of microRNA-875-3p. Overexpression of STON2 could partially abolish the effect of microRNA-875-3p on cell proliferation and cycle of MCF-7 and BCap-37 cells. GACAT1 can participate in the progression of breast cancer by promoting the proliferation and cycle of breast cancer cells. The mechanism may be through the regulation of the level of STON2 by adsorbing microRNA-875-3p.

Sensitivity Analysis of Johnson-Cook Material Constants and Friction Coefficient Influence on Finite Element Simulation of Turning Inconel 718.

The Johnson-Cook (J-C) constitutive model, including five material constants (A, B, n, C, m), and the Coulomb friction coefficient (µ) are critical preprocessed data in machining simulations. Before they become reliable preprocessed data, investigating these parameters' effect on simulation results benefits parameter-selecting. This paper aims to investigate the different influence of five settings of the J-C constitutive equation and Coulomb friction coefficient on the turning simulation results of Inconel 718 under low-high cutting conditions, including residual stress, chip morphology, cutting force and temperature. A three-dimensional (3-D) finite element model was built, meanwhile, the reliability of the model was verified by comparing the experiment with the simulation. Sensitivity analysis of J-C parameters and friction coefficient on simulation results at low-high cutting conditions was carried out by the hybrid orthogonal test. The results demonstrate that the simulation accuracy of Inconel 718 is more susceptible to strain hardening and thermal softening in the J-C constitutive model. The friction coefficient only has significant effects on axial and radial forces in the high cutting condition. The influences of the coefficient A, n, and m on the residual stress, chip thickness, cutting force and temperature are especially significant. As the cutting parameters increase, the effect of the three coefficients will change visibly. This paper provides direction for controlling simulation results through the adjustment of the J-C constitutive model of Inconel 718 and the friction coefficient.

Structure, optical simulation and thermal stability of the HfB2-based high-temperature solar selective absorbing coatings.

Transition metal borides are a kind of potential materials for high-temperature solar thermal applications. In this work, a novel SS/HfB2/Al2O3 tandem absorber was prepared, which exhibited high solar spectrum selectivity (α/ε) of 0.920/0.109. The optical constants of the coating were obtained using spectroscopic ellipsometry, and the dispersion model of the HfB2 layer was modeled with the Tauc-Lorentz dispersion formula. In addition, the reflectance spectrum simulated by the CODE software corroborated well with the experimental results. The thermal stability test indicated that the HfB2/Al2O3 solar absorber coating was thermally stable in vacuum at 600 °C for 2 h. When extending the annealing time to 100 h, the coating could maintain high spectral selectivity after aging at 500 °C irrespective of whether in air or vacuum. All these results indicate that the coating has good solar selectivity and is a promising candidate for high-temperature solar thermal applications.

Investigation on the Tribological Behavior and Wear Mechanism of Five Different Veneering Porcelains.

OBJECTIVES: The primary aim of this research was to investigate the wear behavior and wear mechanism of five different veneering porcelains. METHODS: Five kinds of veneering porcelains were selected in this research. The surface microhardness of all the samples was measured with a microhardness tester. Wear tests were performed on a ball-on-flat PLINT fretting wear machine, with lubrication of artificial saliva at 37°C. The friction coefficients were recorded by the testing system. The microstructure features, wear volume, and damage morphologies were recorded and analyzed with a confocal laser scanning microscope and a scanning electron microscope. The wear mechanism was then elucidated. RESULTS: The friction coefficients of the five veneering porcelains differ significantly. No significant correlation between hardness and wear volume was found for these veneering porcelains. Under lubrication of artificial saliva, the porcelain with higher leucite crystal content exhibited greater wear resistance. Additionally, leucite crystal size and distribution in glass matrix influenced wear behavior. The wear mechanisms for these porcelains were similar: abrasive wear dominates the early stage, whereas delamination was the main damage mode at the later stage. Furthermore, delamination was more prominent for porcelains with larger crystal sizes. SIGNIFICANCE: Wear compatibility between porcelain and natural teeth is important for dental restorative materials. Investigation on crystal content, size, and distribution in glass matrix can provide insight for the selection of dental porcelains in clinical settings.

Host-induced gene silencing of an essential chitin synthase gene confers durable resistance to Fusarium head blight and seedling blight in wheat.

Fusarium head blight (FHB) and Fusarium seedling blight (FSB) of wheat, caused by Fusarium pathogens, are devastating diseases worldwide. We report the expression of RNA interference (RNAi) sequences derived from an essential Fusarium graminearum (Fg) virulence gene, chitin synthase (Chs) 3b, as a method to enhance resistance of wheat plants to fungal pathogens. Deletion of Chs3b was lethal to Fg; disruption of the other Chs gene family members generated knockout mutants with diverse impacts on Fg. Comparative expression analyses revealed that among the Chs gene family members, Chs3b had the highest expression levels during Fg colonization of wheat. Three hairpin RNAi constructs corresponding to the different regions of Chs3b were found to silence Chs3b in transgenic Fg strains. Co-expression of these three RNAi constructs in two independent elite wheat cultivar transgenic lines conferred high levels of stable, consistent resistance (combined type I and II resistance) to both FHB and FSB throughout the T3 to T5 generations. Confocal microscopy revealed profoundly restricted mycelia in Fg-infected transgenic wheat plants. Presence of the three specific short interfering RNAs in transgenic wheat plants was confirmed by Northern blotting, and these RNAs efficiently down-regulated Chs3b in the colonizing Fusarium pathogens on wheat seedlings and spikes. Our results demonstrate that host-induced gene silencing of an essential fungal chitin synthase gene is an effective strategy for enhancing resistance in crop plants under field test conditions.

An atypical winter outbreak of hand, foot, and mouth disease associated with human enterovirus 71, 2010.

BACKGROUND: To analyze the epidemiological characteristics and pathogenic molecular characteristics of an hand, foot, and mouth disease (HFMD) outbreak caused by enterovirus 71 in Linyi City, Shandong Province, China during November 30 to December 28, 2010. METHODS: One hundred and seventy three stool specimens and 40 throat samples were collected from 173 hospitalized cases. Epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. RESULTS: Among the 173 cases reported in December 2010, the male-female ratio was 1.88: 1; 23 cases (13.3%) were severe. The majority of patients were children aged < 5 years (95.4%). Some patients developed respiratory symptoms including runny nose (38.2%), cough (20.2%), and sore throat (14.5%). One hundred and thirty eight EV71 positive cases were identified based on real time reverse-transcription PCR detection and 107 isolates were sequenced with the VP1 region. Phylogenetic analysis of full-length VP1 sequences of 107 Linyi EV71 isolates showed that they belonged to the C4a cluster of the C4 subgenotype and were divided into 3 lineages (Lineage I, II and III). The two amino acid substitutions (Gly and Gln for Glu) at position 145 within the VP1 region are more likely to appear in EV71 isolates from severe cases (52.2%) than those recovered from mild cases (8.3%). CONCLUSION: This outbreak of HMFD was caused by EV71 in an atypical winter. EV71 strains associated with this outbreak represented three separate chains of transmission. Substitution at amino acid position 145 of the VP1 region of EV71 might be an important virulence marker for severe cases. These findings suggest that continued surveillance for EV71 variants has the potential to greatly impact HFMD prevention and control.

Electrochemical microdevice for on-site determination of rice freshness.

An electrochemical microdevice was fabricated for on-site rapid freshness determination of rice. The activity of peroxidase was used as an indicator for freshness. With hydrogen peroxide and hydroquinone as substrates, the enzymatic reaction of peroxidase produced benzoquinone, which was subsequently reduced on a gold working electrode electrochemically. The progress of the enzymatic reaction could clearly be observed in the change of cyclic voltammograms. Distinct differences were observed in the current change between fresh rice and aged rice, reflecting the remaining activity of peroxide. The current also depended on the time at which rice grains were milled. The result agreed well with those obtained by the conventional fluorometric and guaiacol methods. Comparison of results obtained with different numbers of grains showed that even the measurement with a single grain provided fairly consistent data. Furthermore, the existence of grains of different freshness could be identified using a device with multiple sensing sites.

The option value of innovative treatments in the context of chronic myeloid leukemia.

OBJECTIVE: To quantify in the context of chronic myeloid leukemia (CML) the additional value patients receive when innovative treatments enable them to survive until the advent of even more effective future treatments (ie, the "option value"). STUDY DESIGN: Observational study using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry comprising all US patients with CML diagnosed between 2000 and 2008 (N = 9,760). METHODS: We quantified the option value of recent breakthroughs in CML treatment by first conducting retrospective survival analyses on SEER data to assess the effectiveness of TKI treatments, and then forecasting survival from CML and other causes to measure expected future medical progress. We then developed an analytical framework to calculate option value of innovative CML therapies, and used an economic model to value these gains. We calculated the option value created both by future innovations in CML treatment and by medical progress in reducing background mortality. RESULTS: For a recently diagnosed CML patient, the option value of innovative therapies from future medical innovation amounts to 0.76 life-years. This option value is worth $63,000, equivalent to 9% of the average survival gains from existing treatments. Future innovations in CML treatment jointly account for 96% of this benefit. CONCLUSIONS: The option value of innovative treatments has significance in the context of CML and, more broadly, in disease areas with rapid innovation. Incorporating option value into traditional valuations of medical innovations is both a feasible and a necessary practice in health technology assessment.

DR2539 is a novel DtxR-like regulator of Mn/Fe ion homeostasis and antioxidant enzyme in Deinococcus radiodurans.

Transcriptional regulators of the diphtheria toxin repressor (DtxR) family control the expression of genes involved in the uptake of iron and manganese, which is not only necessitous nutrients but also was suggested to be essential for intracellular redox cycling of microorganisms. We identified a unique DtxR homologue (DR2539) with special characteristics from Deinococcus radiodurans, which is known for its extreme resistance to radiation and oxidants. The dr2539 mutant showed higher resistance to hydrogen peroxide than the wild-type strain R1. Intracellular catalase activity assay and semiquantitative PCR analysis demonstrated that this DtxR is a negative regulator of catalase (katE). Furthermore, quantitative real-time PCR, global transcription profile and inductively coupled plasma-mass spectrometry analysis showed that the DtxR is involved in the regulation of antioxidant system by maintaining the intracellular Mn/Fe ion homeostasis of D. radiodurans. However, unlike the other DtxR homologues, the DtxR of D. radiodurans acts as a negative regulator of a Mn transporter gene (dr2283) and as a positive regulator of Fe-dependent transporter genes (dr1219, drb0125) in D. radiodurans.

[Mapping of the loss of heterozygosity for chromosome 1 pter-36.21 in keloid].

OBJECTIVE: The aim of this study was to investigate the loss of heterozygosity (LOH) on chromosome 1 pter-36.21 of keloid in order to locate the deletion areas probably harboring scar suppressor genes. METHODS: Using polymerase chain reaction ( PCR )-denaturing polyacrylamide gel electrophoresis, 25 samples of keloid tissues and peripheral blood were analyzed. RESULTS: 15 out of 25 samples of keloid tissues exhibited LOH in at least one microsatellite locus. There were deletions at more than one locus of one keloid tissue. No MSI was found. The frequency of LOH was remarkably higher in the keloid tissues (n = 25, 15, 60%) than in the normal control samples (n = 25, 1, 4%). The frequency of LOH in D1S243, D1S468, D1S507 and D1S199 was as following: (n= 25, 7, 28%), (n =25, 10, 40%), (n = 25, 13, 52%) and (n= 25, 3, 12%). The frequency of LOH in D1S243, D1S468, D1S507 were statistically significant. CONCLUSION: The most common LOH occurred at D1S243-D1S468-D1S507 might imply the existence of potential tumor suppressor gene of a subset of keloid , while MSI on 1 pter-36.21 may not a crucial event.