Evaluation of the FPMC respiratory panel for detection of respiratory tract pathogens in nasopharyngeal swab and sputum specimens.

OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.

An In-Situ-Tag-Generation Proximity Labeling Technology for Recording Cellular Interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Protein-Targeted Glycan Editing on Living Cells Disrupts KRAS Signaling.

The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.

Indoleamine 2,3-dioxygenase 1 regulates breast cancer tamoxifen resistance through interleukin-6/signal transducer and activator of transcription.

Breast cancer is the primary cause of cancer-related deaths in women. Tamoxifen (TAM) is the preferred drug for treating premenopausal luminal-type breast cancer, but TAM resistance restricts its ability to benefit patients. To date, the mechanism of this resistance remains unclear, and there is currently no effective treatment for reversing it. The expression of indoleamine 2,3-dioxygenase 1 (IDO1) has been shown to be elevated in various malignancies. Here, we aimed to investigate the role of IDO1 in TAM-resistant breast cancer. We confirmed that IDO1 is strongly expressed in TAM-resistant breast cancer, and it mediates drug-resistant cell proliferation, metastasis, and TAM resistance in vivo and in vitro through interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3). We also found that the mechanism by which TAM upregulates IDO1 is dependent on STAT1 activation. In summary, IDO1 regulates TAM resistance and can serve as a novel target for treatment of TAM-resistant breast cancer.

Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis.

BACKGROUND: Chemoresistance limits the therapeutic effect of cisplatin (DDP) on non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) function as important regulators in chemoresistance. This study aimed to explore the regulation of circRNA Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Alpha (circ_PIP5K1A) in DDP resistance. METHODS: The expression analysis of circ_PIP5K1A, micoRNA-493-5p (miR-493-5p) and Rho Associated Coiled-Coil Containing Protein Kinase 1 (ROCK1) was conducted through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell sensitivity was determined using 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cell proliferation and cell viability were evaluated by colony formation assay and MTT assay, respectively. Cell cycle and apoptosis detection was performed via flow cytometry. Cell motility was examined by transwell migration or invasion assay. Dual-luciferase reporter assay was applied to confirm the target binding. ROCK1 protein level was assayed via Western blot. In vivo assay was carried out using xenograft model in mice. RESULTS: Circ_PIP5K1A level was abnormally increased in DDP-resistant NSCLC tissues and cells. Silencing circ_PIP5K1A reduced DDP resistance, proliferation, cell cycle progression and cell motility in DDP-resistant NSCLC cells. Circ_PIP5K1A directly interacted with miR-493-5p in NSCLC cells. The function of circ_PIP5K1A was dependent on the negative regulation of miR-493-5p. MiR-493-5p directly targeted ROCK1 and circ_PIP5K1A regulated the ROCK1 level via acting as a sponge of miR-493-5p. Overexpression of miR-493-5p inhibited chemoresistance and cancer progression by downregulating ROCK1 expression in DDP-resistant NSCLC cells. Circ_PIP5K1A regulated DDP sensitivity in vivo via the miR-493-5p/ROCK1 axis. CONCLUSION: These findings suggested that circ_PIP5K1A upregulated the ROCK1 expression to promote DDP resistance and cancer progression in NSCLC by sponging miR-493-5p.

Synthesis, anti-oomycete activity, and SAR studies of paeonol derivatives.

Three series of sulfonate derivatives of paeonol were synthesized and screened in vitro for their anti-oomycete activity against P. capsici, respectively. Among all the compounds, 4m displayed the best promising and pronounced anti-oomycete activity against P. capsici than zoxamide, with the EC50 values of 24.51 and 26.87 mg/L, respectively. The results show that acetyl and 4-OCH3 are two necessary groups. The existence of these two sites is closely related to the anti-oomycete activity. Relatively speaking, hydroxyl group is well tolerated, and the results showed that after modification of hydroxyl group with sulfonyl, the anti-oomycete activity was significantly increased. [Formula: see text].

Stigma Related to HIV and Drug Use: Layers, Types, and Relations to Mental Health.

Stigma poses considerable challenges to the mental health of people living with HIV who use drugs (PLHWUD). In this study, we explored factors related to different types of stigma (perceived and internalized) attached to layered stigmatizing characters (HIV and drug use) and their mental health influences on PLHWUD. The study used baseline data of an ongoing randomized controlled trial among 241 PLHWUD recruited between March and December 2018 in Vietnam. A structural equation model was used to assess the relationships among different types and layers of stigma and mental health status. Both perceived and internalized drug-related stigma measures were significantly higher than their corresponding HIV-related stigma. HIV-related stigma was negatively associated with mental health status; however, we did not find a significant relationship between drug-related stigma and mental health. Tailored intervention strategies in consideration of types and layers of stigma are needed to address stigma-related challenges faced by PLHWUD.

HCV infection status and care seeking among people living with HIV who use drugs in Vietnam.

HCV co-infection is widespread among people living with HIV who use drugs (PLHWUD). However, HCV testing was inconsistently implemented among PLHWUD. The low infection awareness and mental health challenges together impede PLHWUD's treatment-seeking. The study used baseline data of a randomized controlled trial conducted in Vietnam. HCV infection status was collected through self-report and medical record review. A linear mixed-effects regression model was used to examine the relationships between PLHWUD's perceived barriers to seeking healthcare, their depressive symptoms, and the consistencies in HCV status reports. Among the 181 PLHWUD in the study, one-third (64; 35.4%) had inconsistent self-reports and medical records of HIV infection status. The agreement between the two records was fair (Kappa statistics = 0.43). PLHWUD with consistent HCV infection confirmed by both medical records and self-reports perceived lower levels of healthcare-seeking barriers than those with discrepant HCV reports (estimated difference = -1.59, SE = 0.71, P = 0.027). Depressive symptoms were significantly correlated with healthcare-seeking barriers among those with discrepant HCV results (estimate = 0.17, SE = 0.06, P = 0.007). There is an urgent need to extend HCV screening efforts and increase HCV awareness among PLHWUD. Explicit HCV result notification and integrated mental health support are recommended to facilitate patients' access to needed care.

Using Social Media to Enhance Provider Network for HIV and Harm Reduction Service Integration in Vietnam.

Social media can potentially serve as a platform to coordinate medical care among fragmented health sectors. This paper describes procedures of using social media to enhance antiretroviral therapy (ART) and methadone maintenance treatment (MMT) providers' virtual network for integrated service for HIV-positive people who inject drugs (PWID) in Vietnam. A total of 88 ART and MMT treatment providers participated in person group sessions followed by online virtual support to improve service integration. In-person reunions were held to reinforce Facebook participation and network activities. Content analysis was used to identify keywords and topic categories of the online information exchange. Both MMT and ART providers were actively engaged in online communications. Referral and treatment adherence were the two most frequently discussed topic areas by both the MMT and ART providers. Frequent cross-agency connections were observed. Online provider networks and communities could be built and useful to support treatment providers to improve service integration.

Transcriptome Profiling of Wheat Inflorescence Development from Spikelet Initiation to Floral Patterning Identified Stage-Specific Regulatory Genes.

Early reproductive development in cereals is crucial for final grain number per spike and hence the yield potential of the crop. To date, however, no systematic analyses of gene expression profiles during this important process have been conducted for common wheat (Triticum aestivum). Here, we studied the transcriptome profiles at four stages of early wheat reproductive development, from spikelet initiation to floral organ differentiation. K-means clustering and stage-specific transcript identification detected dynamically expressed homeologs of important transcription regulators in spikelet and floral meristems that may be involved in spikelet initiation, floret meristem specification, and floral organ patterning, as inferred from their homologs in model plants. Small RNA transcriptome sequencing discovered key microRNAs that were differentially expressed during wheat inflorescence development alongside their target genes, suggesting that miRNA-mediated regulatory mechanisms for floral development may be conserved in cereals and Arabidopsis. Our analysis was further substantiated by the functional characterization of the ARGONAUTE1d (AGO1d) gene, which was initially expressed in stamen primordia and later in the tapetum during anther maturation. In agreement with its stage-specific expression pattern, the loss of function of the predominantly expressed B homeolog of AGO1d in a tetraploid durum wheat mutant resulted in smaller anthers with more infertile pollens than the wild type and a reduced grain number per spike. Together, our work provides a first glimpse of the gene regulatory networks in wheat inflorescence development that may be pivotal for floral and grain development, highlighting potential targets for genetic manipulation to improve future wheat yields.

Conversion and pharmacokinetics profiles of a novel pro-drug of 3-n-butylphthalide, potassium 2-(1-hydroxypentyl)-benzoate, in rats and dogs.

Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a novel pro-drug of 3-n-butylphthalide (dl-NBP) that is used to treat ischemic stroke. Currently, dl-PHPB is in phase II-III clinical trials in China. In this study, we investigated the conversion and pharmacokinetics profiles of dl-PHPB in vitro and in vivo. The conversion of dl-PHPB to dl-NBP was pH- and calcium-dependent, and paraoxonase was identified as a major enzyme for the conversion in rat plasma. The pharmacokinetics, tissue distribution and excretion of dl-PHPB were studied and compared with equal-molar doses of dl-NBP in rats and dogs. The in vivo studies showed that dl-PHPB could be quickly and completely converted to dl-NBP. The plasma concentration-time course of converted dl-NBP after intravenous dl-PHPB administration was nearly the same as that after equal-molar dl-NBP. The Cmax and AUC of dl-NBP after oral dl-PHPB administration in rats and dogs were higher by 60% and 170%, respectively, than those after oral dl-NBP administration. Analysis of the tissue distribution of dl-PHPB revealed that converted dl-NBP was primarily distributed in fat, the brain and the stomach. In the brain, the levels of dl-NBP were relatively higher after dl-PHPB treatment by orally than after treatment with equal-molar dl-NBP. Approximately 3%-4% of dl-NBP was excreted within 72 h after dosing with dl-PHPB or dl-NBP, but no dl-PHPB was detected in urine or feces excrements. Our results demonstrate that the conversion of dl-PHPB is fast after oral or intravenous administration. Furthermore, the bioavailability of dl-PHPB was obviously better than that of dl-NBP.

Inhibition of p38 mitogen-activated protein kinase exerts a hypoglycemic effect by improving ß cell function via inhibition of ß cell apoptosis in db/db mice.

The p38 mitogen-activated protein kinase (MAPK) pathway is involved in endoplasmic reticulum stress (ERS) and inflammation, which may play an important role in the pathogenesis of type 2 diabetes (T2DM). This study aimed to investigate whether p38 MAPK contributes to the pathogenesis of T2DM. 6-week-old female db/db mice were randomly assigned to Dmo and Dmi groups, and C57 mice were assigned as controls. The Dmi group was gavaged with the p38 MAPK inhibitor SB203580 for 9 weeks, and the effects on ß cell dysfunction and apoptosis were investigated. db/db mice showed higher food intake, body mass, fasting glucose, and plasma insulin levels than C57 mice. After SB203580 administration, blood glucose was significantly lower. HOMA ß and HOMA IR were improved. Islet mRNA expression levels of the ERS markers were lower. P38 MAPK inhibition reduced blood glucose and improved ß cell function, at least in part by reducing ß cell apoptosis.

Family Related Factors and Concurrent Heroin Use in Methadone Maintenance Treatment in China.

BACKGROUND: The use of heroin during Methadone Maintenance Treatment (MMT) is a challenging problem that contributes to poor treatment outcomes. Families may play an important role in addressing concurrent heroin use during MMT, especially in collectivist societies such as China. OBJECTIVES: In this study, we explored the relationship between family-related factors and concurrent heroin use during MMT in China. METHODS: This study was conducted at 68 MMT clinics in five provinces of China. There were 2,446 MMT clients in the analysis. Demographic information, MMT dosage, family members' heroin use status, family support of MMT, family problem, and self-reported heroin use were collected in a cross-sectional survey. The most recent urinalysis of opiate use was obtained from clinical records. RESULTS: Of the 2,446 participants, 533 (21.79%) self-reported heroin use in the previous seven days or had a positive urine morphine test result in the clinic record. Participants whose family member[s] used heroin were 1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment. Those with family members who totally support them on the MMT were less likely to use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93). CONCLUSIONS: The results highlight the importance of the family's role in concurrent heroin use during MMT programs. The study's findings may have implications for family-based interventions that address concurrent heroin use.

Alcohol Use, HIV Treatment Adherence, and Sexual Risk Among People with a History of Injecting Drug Use in Vietnam.

Alcohol use can limit the effectiveness of antiretroviral therapy (ART) for people living with HIV (PLH) who have a history of injecting drug use. This study described the patterns of alcohol use among PLH with a history of injecting drug use in Vietnam and examined the relationships between alcohol use, adherence to ART, and sexual risks. We utilized cross-sectional data of 109 PLH on ART collected from a randomized controlled intervention trial in Vietnam. Approximately 30 and 46% of the participants were frequent and occasional drinkers, respectively. Frequent drinkers reported the highest number of missed medication days. About 61% of frequent drinkers reported having sex after using alcohol. Additionally, 23, 34, and 24% of nondrinkers, occasional drinkers, and frequent drinkers, respectively, reported inconsistent condom use during sex. Future intervention programs should address the issues of alcohol use and sexual risks to maximize the effectiveness of HIV treatment programs in Vietnam.

Comparison Between Urinalysis Results and Self-Reported Heroin Use Among Patients Undergoing Methadone Maintenance Treatment in China.

BACKGROUND: The validity and concordance of two main measures of drug use behavior, self-report and urinalysis, has long been discussed. More understanding is needed about the underlying factors associated with discordance between these two methods. OBJECTIVES: Describe the pattern and associated factors of discordance between self-reported heroin use and the urinalysis results of opiate use among methadone maintenance therapy (MMT) patients in China. METHODS: A total of 2,448 MMT patients from 68 clinics in five provinces of China participated in a survey, which collected information on demographics, drug use and MMT-related factors, depressive symptoms, and drug avoidance self-efficacy. The most recent urine morphine test result was obtained from medical records and compared with self-reported heroin use. Participants who had urinalysis within 14 days of the survey were included in the analysis. RESULTS: Among the 1,092 participants, 70 (6.4%) self-reported heroin use and 195 (17.9%) had positive urinalysis results. The over-reporters group had significantly higher education, and the under-reporters had significantly higher level of drug-avoidance self-efficacy and lower level of depressive symptoms. Among the participants who either self-reported heroin use or had positive urinalysis results, being young, having higher education, and having lower level of depressive symptoms were associated with discordance between self-reports and urinalysis results. CONCLUSION: The combination of both measures in assessing drug use behavior seems necessary. The validity of self-report should be considered differently based on demographic and psychosocial characteristics.

[A retrospective analysis of 6 children with Duchenne muscular dystrophy].

OBJECTIVE: To analyze the clinical features of 6 children with Duchenne muscular dystrophy (DMD) and review related literature, and to provide a basis for early diagnosis and effective treatment of this disease. METHODS: A retrospective analysis was performed on the clinical data of 6 children with DMD who were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2015. RESULTS: All the 6 cases were boys without a family history of DMD, and the age of diagnosis of DMD was 1.2-11.5 years. All patients had insidious onset and increases in alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, creatine kinase (CK), and creatine kinase-MB, particularly CK, which was 3.3-107.2 times the normal level. Their gene detection results all showed DMD gene mutation. The gene detection results of two children's mothers showed that they carried the same mutant gene. The muscle biopsy in one case showed that the pathological changes confirmed the diagnosis of DMD. The level of CK in one case declined by 77.0% 5 days after umbilical cord blood mesenchymal stem cell transplantation. CONCLUSIONS: For boys with abnormal serum enzyme levels and motor function, DMD should be highly suspected. It should be confirmed by CK and DMD gene detection as soon as possible. And the progression of the disease could be delayed by early intervention for protecting the remaining normal muscle fibers.

First principles prediction of interfacial magnetoelectric coupling in tetragonal La2/3Sr1/3MnO3/BiFeO3 multiferroic superlattices.

The electronic structure and magnetic properties of the tetragonal La2/3Sr1/3MnO3/BiFeO3 multiferroic superlattices with different interfacial terminations have been studied by first-principles calculations. Our results for all the models of the tetragonal La2/3Sr1/3MnO3/BiFeO3 superlattices exhibit a metallic electronic structure. More importantly, we find that the magnetoelectric coupling can be realized in the tetragonal La2/3Sr1/3MnO3/BiFeO3 heterostructures by means of exchange bias, which can be attributed to the interfacial exchange coupling. These findings are useful for magnetoelectrically controlled spintronic devices.

A cooperative model for IS security risk management in distributed environment.

Given the increasing cooperation between organizations, the flexible exchange of security information across the allied organizations is critical to effectively manage information systems (IS) security in a distributed environment. In this paper, we develop a cooperative model for IS security risk management in a distributed environment. In the proposed model, the exchange of security information among the interconnected IS under distributed environment is supported by Bayesian networks (BNs). In addition, for an organization's IS, a BN is utilized to represent its security environment and dynamically predict its security risk level, by which the security manager can select an optimal action to safeguard the firm's information resources. The actual case studied illustrates the cooperative model presented in this paper and how it can be exploited to manage the distributed IS security risk effectively.

A fault isolation strategy for industrial processes using outlier-degree-based variable contributions.

In industrial process monitoring, it is always a challenging and practical problem to analyze the causes of the system fault by isolating true fault variables from vast amounts of process data. However, the phenomenon of smearing effect occurs by using the traditional contribution analysis-based isolation methods since the defined isolation indices of different variables affect each other. In this paper, a new fault isolation method is proposed based on local outlier factor and improved k-nearest neighbor rule aiming to improve the isolation accuracy. Firstly, the nearest neighbors of each sample are obtained along the direction of a specific variable. Based on the nearest neighbors, the outlier-degree value of the variable is calculated and regarded as the contribution of the variable. Then, the contribution of the variable in all samples are obtained in the same way, among which the maximum one is selected as the isolation threshold value of this variable. During the online monitoring, the contribution of the variable in the newly collected sample is calculated in real time. Once the contribution is greater than the threshold, the variable is judged to be the dominant factor causing the system fault. Two cases on numerical example and Tennessee Eastman process are conducted to evaluate the effectiveness of the proposed method.