Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease.

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

Gut-oriented disease modifying therapy for Parkinson's disease.

Neuropathology studies have shown that the pathognomonic feature of Parkinson's disease (PD), one of the most common neurodegenerative disorders, may start from the gut enteric nervous system and then spread to the central dopaminergic neurons through the gut-brain axis. With the advent of metagenomic sequencing and metabolomic analysis, a plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared with unaffected controls. Currently, although dopaminergic treatments and deep brain stimulation can provide some symptomatic benefits for motor symptoms of the disease, their long-term use is problematic. A mechanism-targeted therapy to halt the neurodegeneration is lacking. The recently observed gut microenvironmental changes in the early stages of the disease play a vital role in the PD pathogenesis. Patients whose disease begins in the gut may benefit most from interventions that target the gut microenvironments. In this review, we will summarize the current studies demonstrating multifunctional roles of gut microbiota in the gut-brain axis of PD and the currently available evidence for targeting the gut microbiota as a novel approach to potential disease-modifying therapy in PD.

Amelioration of Maternal Immune Activation-Induced Autism Relevant Behaviors by Gut Commensal Parabacteroides goldsteinii.

Autism spectrum disorder (ASD) is characterized by cognitive inflexibility and social deficits. Probiotics have been demonstrated to play a promising role in managing the severity of ASD. However, there are no effective probiotics for clinical use. Identifying new probiotic strains for ameliorating ASD is therefore essential. Using the maternal immune activation (MIA)-based offspring ASD-like mouse model, a probiotic-based intervention strategy was examined in female mice. The gut commensal microbe Parabacteroides goldsteinii MTS01, which was previously demonstrated to exert multiple beneficial effects on chronic inflammation-related-diseases, was evaluated. Prenatal lipopolysaccharide (LPS) exposure induced leaky gut-related inflammatory phenotypes in the colon, increased LPS activity in sera, and induced autistic-like behaviors in offspring mice. By contrast, P. goldsteinii MTS01 treatment significantly reduced intestinal and systemic inflammation and ameliorated disease development. Transcriptomic analyses of MIA offspring indicated that in the intestine, P. goldsteinii MTS01 enhanced neuropeptide-related signaling and suppressed aberrant cell proliferation and inflammatory responses. In the hippocampus, P. goldsteinii MTS01 increased ribosomal/mitochondrial and antioxidant activities and decreased glutamate receptor signaling. Together, significant ameliorative effects of P. goldsteinii MTS01 on ASD relevant behaviors in MIA offspring were identified. Therefore, P. goldsteinii MTS01 could be developed as a next-generation probiotic for ameliorating ASD.

Impact on Macrolide Resistance of Genetic Diversity of Mycobacterium abscessus Species.

Our previous study identified that the Mycobacterium abscessus subsp. abscessus T28 sequevar does not fully represent inducible macrolide resistance. Thus, we initiated a correlation study between genotypes and phenotypes. In total, 75 isolates from patients with skin and soft tissue infections were enrolled in the study. These strains were tested against 11 antimycobacterial agents using Sensitire RAPMYCO plates and the CLSI-recommended broth microdilution method. In order to analyze erm(41) and partial hsp65, rpoB, secA1, and rrl genes, bacterial genomic DNA was extracted from bacteria. The MEGA X software was used for phylogenetic analyses. The most active agents against most M. abscessus species were amikacin and tigecycline. Clarithromycin was effective toward M. abscessus subsp. massiliense and nearly all M. abscessus subsp. abscessus C28 sequevars. Two varieties of M. abscessus subsp. abscessus T28 sequevars did not represent inducible macrolide resistance. Most M. abscessus species showed intermediate susceptibility to cefoxitin and imipenem. Six additional agents were less effective against M. abscessus species. Following phylogenetic analyses, two outliers of M. abscessus subsp. abscessus T28 sequevars seem to represent no inducible macrolide resistance. In addition, we discovered genetic mosaicism of hsp65, rpoB, and secA1 in M. abscessus species was common. T28 sequevars of M. abscessus subsp. abscessus do not fully represent inducible macrolide resistance. The outlier of erm(41) phylogeny of the M. abscessus subsp. abscessus T28 sequevar is possibly due to macrolide susceptibility. Evaluation of the antimicrobial susceptibility of M. abscessus species is a reliable tool for assisting physicians in selecting the most effective antimycobacterial agent(s). IMPORTANCE Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm(41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl. However, not all M. abscessus subsp. abscessus T28 sequevars have inducible macrolide resistance. Exploration of the mechanism of macrolide resistance requires an understanding of genetic diversity. The genetic mosaicism of the erm(41), rpoB, hsp65, and secA1 genes within three subspecies of M. abscessus species is not uncommon. The T28 sequevar of erm(41) confers inducible macrolide resistance to the genetic mosaic strain. The development of new anti-M. abscessus species infection overcoming inducible macrolide resistance and/or acquired macrolide resistance is a crucial issue.

Association between Gut Microbiota and Emotional-Behavioral Symptoms in Children with Attention-Deficit/Hyperactivity Disorder.

Previous studies have explored the role of the microbiome in attention-deficit/hyperactivity disorder (ADHD). However, whether the microbiome is correlated with emotional-behavioral disturbances, the most common comorbid symptom of ADHD, remains unclear. We established a cross-sectional study in which 6- to 18-year-old children with ADHD who were receiving no medication and a healthy control group of children without ADHD were recruited to analyze their microbiome composition. Microbiota of fecal samples were collected and analyzed using a 16s rRNA gene sequencing approach. In comparison with the healthy control group, the gut microbiota in children with ADHD exhibited significantly lower beta diversity. The abundance of the phylum Proteobacteria and the genera Agathobacter, Phascolarctobacterium, Prevotella_2, Acidaminococcus, Roseburia, and Ruminococcus gnavus group was increased in the ADHD group compared with the healthy group. Linear discriminant effect size (LEfSe) analysis was used to highlight specific bacteria phylotypes that were differentially altered between the ADHD and control groups. A regression analysis was performed to investigate the association between microbiota and emotional-behavioral symptoms in children with ADHD. A significant association was noted between withdrawal and depression symptoms and Agathobacter (p = 0.044), and between rule-breaking behavior and the Ruminococcus gnavus group (p = 0.046) after adjusting for sex, age, and the ADHD core symptoms score. This study advances the knowledge of how gut microbiota composition may contribute to emotional-behavioral symptoms in children with ADHD. The detailed mechanisms underlying the role of the gut microbiota in ADHD pathophysiology still require further investigation.

Gut Commensal Parabacteroides goldsteinii MTS01 Alters Gut Microbiota Composition and Reduces Cholesterol to Mitigate Helicobacter pylori-Induced Pathogenesis.

Helicobacter pylori infection is closely associated with various gastrointestinal diseases and poses a serious threat to human health owing to its increasing antimicrobial resistance. H. pylori possesses two major virulence factors, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), which are involved in its pathogenesis. Probiotics have recently been used to eradicate H. pylori infection and reduce the adverse effects of antibiotic-based therapies. Parabacteroides goldsteinii MTS01 is a novel next-generation probiotic (NGP) with activities that can alleviate specific diseases by altering the gut microbiota. However, the mechanism by which P. goldsteinii MTS01 exerts its probiotic effects against H. pylori infection remains unclear. Our results showed that administration of P. goldsteinii MTS01 to H. pylori-infected model mice altered the composition of the gut microbiota and significantly reduced serum cholesterol levels, which mitigated H. pylori-induced gastric inflammation. In addition, the pathogenic effects of H. pylori VacA and CagA on gastric epithelial cells were markedly abrogated by treatment with P. goldsteinii MTS01. These results indicate that P. goldsteinii MTS01 can modulate gut microbiota composition and has anti-virulence factor functions, and thus could be developed as a novel functional probiotic for reducing H. pylori-induced pathogenesis.

Clinical manifestations and antimicrobial susceptibility of Nocardia species at a tertiary hospital in Taiwan, 2011-2020.

BACKGROUND: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance. METHODS: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method. RESULTS: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time. CONCLUSION: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.

Impact of Metabolic Surgery on Gut Microbiota and Sera Metabolomic Patterns among Patients with Diabetes.

Metabolic surgery is a promising treatment for obese individuals with type 2 diabetes mellitus (T2DM), but the mechanism is not completely understood. Current understanding of the underlying ameliorative mechanisms relies on alterations in parameters related to the gastrointestinal hormones, biochemistry, energy absorption, the relative composition of the gut microbiota, and sera metabolites. A total of 13 patients with obesity and T2DM undergoing metabolic surgery treatments were recruited. Systematic changes of critical parameters and the effects and markers after metabolic surgery, in a longitudinal manner (before surgery and three, twelve, and twenty-four months after surgery) were measured. The metabolomics pattern, gut microbiota composition, together with the hormonal and biochemical characterizations, were analyzed. Body weight, body mass index, total cholesterol, triglyceride, fasting glucose level, C-peptide, HbA1c, HOMA-IR, gamma-glutamyltransferase, and des-acyl ghrelin were significantly reduced two years after metabolic surgery. These were closely associated with the changes of sera metabolomics and gut microbiota. Significant negative associations were found between the Eubacterium eligens group and lacosamide glucuronide, UDP-L-arabinose, lanceotoxin A, pipercyclobutanamide B, and hordatine B. Negative associations were identified between Ruminococcaceae UCG-003 and orotidine, and glucose. A positive correlation was found between Enterococcus and glutamic acid, and vindoline. Metabolic surgery showed positive effects on the amelioration of diabetes and metabolic syndromes, which were closely associated with the change of sera metabolomics, the gut microbiota, and other disease-related parameters.

Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition.

Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have indicated that exposure to these antibiotic residues in food may be associated with childhood obesity. Herein, the effect of exposure to a residual dose of tylosin-an antibiotic growth promoter-on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of tylosin were found to facilitate high-fat-diet-induced obesity, induce insulin resistance, and perturb gut microbiota composition in mice. The obesity-related phenotypes were transferrable to germfree recipient mice, indicating that the effects of a TMDI dose of tylosin on obesity and insulin resistance occurred mainly via alteration of the gut microbiota. Tylosin TMDI exposure restricted to early life, the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to tylosin TMDI doses was sufficient to modify the ratio of primary to secondary bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low doses of antibiotic residues, whether continuously or in early life, could exert long-lasting effects on host metabolism by altering the gut microbiota and its metabolites. IMPORTANCE This study demonstrates that even with limited exposure in early life, a residual dose of tylosin might cause long-lasting metabolic disturbances by altering the gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.

High-flow nasal cannula improves respiratory impedance evaluated by impulse oscillometry in chronic obstructive pulmonary disease patients: a randomised controlled trial.

Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, respiratory rate, pulse rate, and blood pressure at the time of pre-HFNC, post-HFNC, pre-NC, and post-NC, were collected and analysed using SPSS (version 25.0, IBM, Armonk, NY, USA). The IOS measurement indicated that HFNC significantly improved R5, R5% predicted, R5-R20, X5-predicted, and Fres compared with NC, whereas no significant difference was observed through the PFT measurement. The beneficial effect of HFNC in improving small airway resistance and peripheral lung reactance compared with that of NC in patients with stable COPD was confirmed through IOS measurement.Trial registration: ClinicalTrials.gov NCT05130112 22/11/2021.

Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration. DESIGN: A murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays. RESULTS: Gut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway. CONCLUSION: The gut microbiota-lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

Different Associations between Tonsil Microbiome, Chronic Tonsillitis, and Intermittent Hypoxemia among Obstructive Sleep Apnea Children of Different Weight Status: A Pilot Case-Control Study.

The tonsil microbiome is associated with chronic tonsillitis and obstructive sleep apnea (OSA) in children, and the gut microbiome is associated with host weight status. In this study, we hypothesized that weight status may be associated with clinical profiles and the tonsil microbiome in children with OSA. We prospectively enrolled 33 non-healthy-weight (cases) and 33 healthy-weight (controls) pediatric OSA patients matched by the proportion of chronic tonsillitis. Differences in the tonsil microbiome between the non-healthy-weight and healthy-weight subgroups and relationships between the tonsil microbiome and clinical variables were investigated. Non-healthy weight was associated with significant intermittent hypoxemia (oxygen desaturation index, mean blood saturation (SpO2), and minimal SpO2) and higher systolic blood pressure percentile, but was not related to the tonsil microbiome. However, chronic tonsillitis was related to Acidobacteria in the non-healthy-weight subgroup, and oxygen desaturation index was associated with Bacteroidetes in the healthy-weight subgroup. In post hoc analysis, the children with mean SpO2 ≤ 97% had reduced α and ß diversities and a higher abundance of Bacteroidetes than those with mean SpO2 > 97%. These preliminary findings are novel and provide insights into future research to understand the pathogenesis of the disease and develop personalized treatments for pediatric OSA.

Outcome of full digital workflow for orthognathic surgery planning in the treatment of asymmetric skeletal class III deformity.

BACKGROUND/PURPOSE: Studies have reported the advantages of digital imaging-assisted orthognathic surgery planning, but there is scarce information about a full digital planning modality. This study evaluated the 3D cephalometric-based and patient-reported outcomes of a full digital workflow for orthognathic surgery planning in the treatment of asymmetric maxillomandibular disharmony. METHODS: A postoperative 3D image dataset of 30 Taiwanese Chinese patients with asymmetric skeletal Class III deformities who underwent full digital planning for two-jaw surgery were retrieved from the authors' database. The 3D cephalometric data (dental, skeletal, and soft tissue evaluations) were compared to the ethnicity-matched 3D cephalometric normative values. Patient-reported outcome measure tools regarding postoperative overall appearance and satisfaction with facial areas (ranging from 0 to 100 and 0 to 10, respectively) were administered. The number of needed or requested revisionary surgery was collected. RESULTS: No difference (all p > 0.05) was observed between the orthognathic-surgery-treated patients and the normative value for most of the tested 3D cephalometric parameters, with the exception (p < 0.05) of three mandible and occlusal-plane-related parameters. Both patient-reported outcome measure tools showed that patients' satisfaction with their postoperative appearance was high for overall face (89.7 ± 4.5) and specific facial regions (nose, 7.1 ± 1.3; lip, 8.3 ± 1.6; upper gum, 8.5 ± 1.2; cheek, 8.8 ± 1.1; chin, 9.2 ± 1.2; and teeth, 9.3 ± 0.8), with no need for revisionary surgery. CONCLUSION: The patients treated with a full 3D digital planning-assisted two-jaw surgery had a similar 3D dental relation, facial convexity, and symmetry compared to healthy ethnicity-matched individuals, and they reported higher satisfaction levels with their postoperative facial appearance results.

Quantifying spatial heterogeneity of vulnerability to short-term PM2.5 exposure with data fusion framework.

The current estimations of the burden of disease (BD) of PM2.5 exposure is still potentially biased by two factors: ignorance of heterogeneous vulnerabilities at diverse urbanization levels and reliance on the risk estimates from existing literature, usually from different locations. Our objectives are (1) to build up a data fusion framework to estimate the burden of PM2.5 exposure while evaluating local risks simultaneously and (2) to quantify their spatial heterogeneity, relationship to land-use characteristics, and derived uncertainties when calculating the disease burdens. The feature of this study is applying six local databases to extract PM2.5 exposure risk and the BD information, including the risks of death, cardiovascular disease (CVD), and respiratory disease (RD), and their spatial heterogeneities through our data fusion framework. We applied the developed framework to Tainan City in Taiwan as a use case estimated the risks by using 2006-2016 emergency department visit data, air quality monitoring data, and land-use characteristics and further estimated the BD caused by daily PM2.5 exposure in 2013. Our results found that the risks of CVD and RD in highly urbanized areas and death in rural areas could reach 1.20-1.57 times higher than average. Furthermore, we performed a sensitivity analysis to assess the uncertainty of BD estimations from utilizing different data sources, and the results showed that the uncertainty of the BD estimations could be contributed by different PM2.5 exposure data (20-32%) and risk values (0-86%), especially for highly urbanized areas. In conclusion, our approach for estimating BD based on local databases has the potential to be generalized to the developing and overpopulated countries and to support local air quality and health management plans.

Cheek soft tissue prediction in cleft orthognathic surgery: A 3D computer-assisted investigation with comparative analysis.

BACKGROUND: The Le Fort I maxillary advancement and rotational movement have been adopted to treat patients with cleft-related skeletal Class III pattern and anteromedial cheek soft tissue deficiency, but cleft-specific cheek soft tissue prediction data are insufficient. This 3D imaging-based study addressed the issue. METHODS: 3D craniofacial soft tissue and bone models were created from 32 consecutive patients who received computer-aided two-jaw orthognathic surgery for the correction of cleft-related Class III deformity and cheek soft tissue deficiency. Using superimposed 3D models, the cheek volumetric change, the cheek sagittal movement, and the 3D cheek mass position were calculated. 3D data from orthognathic surgery-treated patients with no cleft (noncleft cohort) and individuals with no facial deformity (3D norm value) were retrieved for comparative analysis. RESULTS: Surgical maxillary advancement (p < 0.001) but not maxillary clockwise rotation (p > 0.05) had a significant impact on the cheek soft tissue change, with prediction models showing that maxillary advancement elucidated 77 and 79% of this change on the cleft and noncleft sides, respectively. Cleft cohort (0.46±0.12) had a significantly (p < 0.001) smaller cheek soft-to-hard tissue ratio than that of the noncleft cohort (0.73±0.13). Cleft maxillary advancements >4 mm resulted in a 3D cheek mass position (2.1±1.1 mm) similar (p > 0.05) to the 3D norm value (2.2±1.2 mm), but different (p = 0.037) from the noncleft cohort (2.38±0.7 mm). CONCLUSION: This study showed that maxillary advancement but not the maxillary rotation affects the cheek soft tissue change, and the predictive values and comparative data could assist the orthodontist-surgeon interaction during preoperative planning and patient counseling.

Application of a health index using PM2.5 concentration reductions for evaluating cross-administrative region air quality policies.

The primary goal of air quality policies is to reduce the impact of air pollution on human health, in particular, it is very important in the attainment-closing geographic areas with densely populated like Taiwan. Air quality policies in general only consider the reduction of emission as well as concentration, in order to highlight the effects of air pollution reduction responded on human health, a health index using PM2.5 concentration reductions (HI-cr) was adopted to evaluate air quality policies in this study. To investigate priorities of cross-administrative region air quality policies, the HI-cr were calculated by using annual results of atmospheric modeling and air quality modeling, which involved the meteorological effect and spatial distribution of air pollution. By studying the emission reduction targets of three administrative regions, Taichung, Changhwa, and Nantau in the Central Taiwan, 8 reduction scenarios were designed and examined. It is found that HI-cr can present detailed information in human health.From the results of adaptability assessement based on health, the equal reduction of emission in present air quality policy gave the most concentration reduction area with lower HI-cr. But according to the analysis in different proportion of emission reduction scenarios, it found that emission reduced more in the most population region, even the concentration reduction is not the highest but HI-cr increased. According to the analysis of different emission reduction policies, this study suggests HI-cr is an important index to evaluate the air pollution control policies instead of considering the impact of air pollutant concentrations only, especially in cross-administrative regions.Implications: In this study, we present a modified health index, HI-cr, to determine the priority of cross-administrative air quality policies using PM2.5 concentration reduction. HI-cr is adaptable for any types of geography, in particular for areas where the air quality is almost attainment like Taiwan. Cross-administrative air quality policies could be evaluated using HI-cr, it could highlight the high performance on population health improvement rather than high concentration reduction. In particular, for economies where the air quality is almost attainment and with complex terrain and dense population, air quality policies should consider the health prevention issues.

Role of gut microbiota in identification of novel TCM-derived active metabolites.

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

Gold nanoparticle-assisted plasmonic enhancement for DNA detection on a graphene-based portable surface plasmon resonance sensor.

The impact of different gold nanoparticle (GNP) structures on plasmonic enhancement for DNA detection is investigated on a few-layer graphene (FLG) surface plasmon resonance (SPR) sensor. Two distinct structures of gold nano-urchins (GNu) and gold nanorods (GNr) were used to bind the uniquely designed single-stranded probe DNA (ssDNA) of Mycobacterium tuberculosis complex DNA. The two types of GNP-ssDNA mixture were adsorbed onto the FLG-coated SPR sensor through the π-π stacking force between the ssDNA and the graphene layer. In the presence of complementary single-stranded DNA, the hybridization process took place and gradually removed the probes from the graphene surface. From SPR sensor preparation, the annealing process of the Au layer of the SPR sensor effectively enhanced the FLG coverage leading to a higher load of the probe DNA onto the sensing interface. The FLG was shown to be effective in providing a larger surface area for biomolecular capture due to its roughness. Carried out in the DNA hybridization study with the SPR sensor, GNu, with its rough and spiky structures, significantly reinforced the overall DNA hybridization signal compared with GNr with smooth superficies, especially in capturing the probe DNA. The DNA hybridization detection assisted by GNu reached the femtomolar range limit of detection. An optical simulation validated the extreme plasmonic field enhancement at the tip of the GNu spicules. The overall integrated approach of the graphene-based SPR sensor and GNu-assisted DNA detection provided the proof-of-concept for the possibility of tuberculosis disease screening using a low-cost and portable system to be potentially applied in remote or third-world countries.

Health risk assessment of trace elements of ambient PM2.5 under monsoon patterns.

In order to identify the contribution to health risk derived from various emission sources, this study investigated monsoon variations in PM2.5 mass and concentrations of the associated trace elements in a region with complex pollution sources in central Taiwan. This study applied the Chemical Mass Balance model to analyze the source contribution of PM2.5. The source apportionment to obtain the risk contribution of different sources were conducted for different monsoon periods according to the monsoon patterns. In this way, the contributions of individual sources and chemicals to health risk under different monsoon types can be understood to support development of effective control strategies. Among the top contributors of PM2.5 during the north-east monsoon were Secondary Aerosol 28.93% >Coal Boiler 19.82% >Crustal Dust 15.99%; in south-west monsoon were Coal Boiler 37.29% >Traffic Emission 21.19% >Secondary Aerosol 17.84%. The total risk of cancer was above the acceptable risk (3.07 × 10-6), while the non-carcinogenic risk was within the acceptable range (0.262). The variation in the concentration and composition of PM2.5 was related to the change of monsoon type. During the north-east monsoon, the air mass had a long transmission distance and the PM2.5 concentration was relatively high. During the south-west monsoon, the air mass had a short transmission distance and the composition was mainly influenced by nearby emission sources, which resulted in higher risk due to chemical characteristics. To provide sound air quality management, attention should be paid to the composition of PM2.5 in addition to its concentration.

Identification of hsa-miR-1275 as a Novel Biomarker Targeting MECP2 for Human Epilepsy of Unknown Etiology.

Epilepsy affects around 70 million people worldwide, with a 65% rate of unknown etiology. This rate is known as epilepsy of unknown etiology (EUE). Dysregulation of microRNAs (miRNAs) is recognized to contribute to mental disorders, including epilepsy. However, miRNA dysregulation is poorly understood in EUE. Here, we conducted miRNA expression profiling of EUE by microarray technology and identified 57 pathogenic changed miRNAs with significance. The data and bioinformatic analysis results indicated that among these miRNAs, hsa-microRNA (miR)-1275 was highly associated with neurological disorders. Subsequently, new samples of serum and cerebrospinal fluid were collected for validation of hsa-miR-1275 expression by TaqMan assays. Results show that hsa-miR-1275 in serums of EUE were increased significantly, but in cerebrospinal fluid, the miRNA was decreased. Moreover, the MECP2 gene was selected as a hsa-miR-1275 target based on target prediction tools and gene ontology analysis. Validation of in vitro tests proved that MECP2 expression was specifically inhibited by hsa-miR-1275. Additionally, overexpression of hsa-miR-1275 can elevate expression of nuclear factor κB (NF-κB) and promote cell apoptosis. Taken together, hsa-miR-1275 might represent a novel biomarker targeting MECP2 for human EUE.