ABSTRACT
OBJECTIVE: The purpose of this study is to compare radiological and clinical outcomes between alternate levels (C4 and C6) and all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. METHODS: Ninety-six patients who underwent C3-6 unilateral open-door laminoplasty with alternate levels mini-plate fixation (54 patients in group A) or all levels mini-plate fixation (42 patients in group B) between September 2014 and September 2019 were reviewed in this study. Radiologic and clinical outcomes were assessed. Clinical results included Visual Analogue Scale (VAS) of axial neck pain and Japanese Orthopedic Association (JOA) score. Radiographic results included cervical range of motion (ROM), cervical curvature index (CCI), and the spinal canal expansive parameters including open angle, anteroposterior diameter (APD), and Pavlov`s ratio. RESULTS: There was no significant difference in VAS, JOA score, ROM, and CCI between two groups. There was no significant difference in canal expansion postoperatively between two groups. However, open angle, APD, and Pavlov`s ratio in group A decreased significantly during the follow-up. In group B, APD, Pavlov`s ratio, and open angle were maintained until the final follow-up. There was no hardware failure or lamina reclosure occurred in both groups during the follow-up. The mean cost of group B was higher than that of group A. CONCLUSIONS: Despite the differences in the maintenance of canal expansion, alternate levels mini-plate fixation can achieve similar clinical outcomes as all levels mini-plate fixation in C3-6 unilateral open-door laminoplasty. As evidenced in this study, we believe C3-6 laminoplasty with alternate levels (C4 and C6) mini-plate fixation is an economical, effective, and safe treatment method.
Subject(s)
Bone Plates , Cervical Vertebrae , Laminoplasty , Humans , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Laminoplasty/methods , Female , Middle Aged , Retrospective Studies , Male , Aged , Treatment Outcome , Range of Motion, Articular , Adult , Neck Pain/etiology , Neck Pain/surgeryABSTRACT
Menaquinone-7 (MK-7), a form of vitamin K2, supports bone health and prevents arterial calcification. Microbial fermentation for MK-7 production has attracted widespread attention because of its low cost and short production cycles. However, insufficient substrate supply, unbalanced precursor synthesis, and low catalytic efficiency of key enzymes severely limited the efficiency of MK-7 synthesis. In this study, utilizing Bacillus subtilis BSAT01 (with an initial MK-7 titer of 231.0 mg/L) obtained in our previous study, the glycerol metabolism pathway was first enhanced to increase the 3-deoxy-arabino-heptulonate 7-phosphate (DHAP) supply, which led to an increase in MK-7 titer to 259.7 mg/L. Subsequently, a combination of knockout strategies predicted by the genome-scale metabolic model etiBsu1209 was employed to optimize the central carbon metabolism pathway, and the resulting strain showed an increase in MK-7 production from 259.7 to 318.3 mg/L. Finally, model predictions revealed the methylerythritol phosphate pathway as the major restriction pathway, and the pathway flux was increased by heterologous introduction (Introduction of Dxs derived from Escherichia coli) and fusion expression (End-to-end fusion of two enzymes by a linker peptide), resulting in a strain with a titer of 451.0 mg/L in a shake flask and 474.0 mg/L in a 50-L bioreactor. This study achieved efficient MK-7 synthesis in B. subtilis, laying the foundation for large-scale MK-7 bioproduction.
ABSTRACT
Recently, the transformer has achieved notable success in remote sensing (RS) change detection (CD). Its outstanding long-distance modeling ability can effectively recognize the change of interest (CoI). However, in order to obtain the precise pixel-level change regions, many methods directly integrate the stacked transformer blocks into the UNet-style structure, which causes the high computation costs. Besides, the existing methods generally consider bitemporal or differential features separately, which makes the utilization of ground semantic information still insufficient. In this paper, we propose the multiscale dual-space interactive perception network (MDIPNet) to fill these two gaps. On the one hand, we simplify the stacked multi-head transformer blocks into the single-layer single-head attention module and further introduce the lightweight parallel fusion module (LPFM) to perform the efficient information integration. On the other hand, based on the simplified attention mechanism, we propose the cross-space perception module (CSPM) to connect the bitemporal and differential feature spaces, which can help our model suppress the pseudo changes and mine the more abundant semantic consistency of CoI. Extensive experiment results on three challenging datasets and one urban expansion scene indicate that compared with the mainstream CD methods, our MDIPNet obtains the state-of-the-art (SOTA) performance while further controlling the computation costs.
ABSTRACT
Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that causes substantial economic losses in the swine industry worldwide. The PDCoV NS6 protein is an accessory protein that plays a pivotal role in the viral life cycle and immune evasion. However, the functions of NS6 and its role in PDCoV pathogenesis remain largely unknown. In this study, we prepared a monoclonal antibody (mAb) 5-A11 that specifically recognizes the PDCoV NS6 protein. The mAb 5-A11 exhibited high specificity for PDCoV, with no cross-reactivity with several major porcine pathogenic viruses. Furthermore, the epitope recognized by mAb 5-A11 was precisely mapped to residues 70EYGSIYGKDFI80 of the NS6 protein using Western blot analysis. Notably, this epitope is highly conserved among different PDCoV isolates. Substantial variations were observed when comparing this epitope with the corresponding regions in the NS6 proteins of other δ coronaviruses, suggesting potential differences in the structure, function, and antigenicity of their NS6 proteins. Our findings provide valuable tools and insights for further elucidating the functions of the NS6 protein and its role in PDCoV pathogenesis, as well as for developing diagnostic and therapeutic strategies against PDCoV infection.
Subject(s)
Antibodies, Monoclonal , Deltacoronavirus , Epitopes , Viral Nonstructural Proteins , Animals , Antibodies, Monoclonal/immunology , Swine , Deltacoronavirus/immunology , Viral Nonstructural Proteins/immunology , Viral Nonstructural Proteins/metabolism , Epitopes/immunology , Epitope Mapping , Coronavirus Infections/immunology , Coronavirus Infections/virology , Antibodies, Viral/immunology , Swine Diseases/virology , Swine Diseases/immunology , Mice , Amino Acid Sequence , Mice, Inbred BALB CABSTRACT
INTRODUCTION: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study. METHODS: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo. RESULTS: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24. DISCUSSION: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE.
ABSTRACT
BACKGROUND: Extensive evidence indicates that both lifestyle factors and air pollution are strongly associated with all-cause mortality. However, little studies in this field have integrated these two factors in order to examine their relationship with mortality and explore potential interactions. METHODS: A cohort of 271,075 participants from the UK Biobank underwent analysis. Lifestyles in terms of five modifiable factors, namely smoking, alcohol consumption, physical activity, diet, and sleep quality, were classified as unhealthy (0-1 score), general (2-3 score), and healthy (4-5 score). Air pollution, including particle matter with a diameter ≤ 2.5 µm (PM2.5), particulate matter with a diameter ≤ 10 µm (PM10), particulate matter with a diameter 2.5-10 µm (PM2.5-10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), was divided into three levels (high, moderate, and low) using Latent Profile Analysis (LPA). Cox proportional hazard regression analysis was performed to examine the links between lifestyle, air pollution, and all-cause mortality before and after adjustment for potential confounders. Restricted cubic spline curves featuring three knots were incorporated to determine nonlinear relationships. The robustness of the findings was assessed via subgroup and sensitivity analyses. RESULTS: With unhealthy lifestyles have a significantly enhanced risk of death compared to people with general lifestyles (HR = 1.315, 95% CI, 1.277-1.355), while people with healthy lifestyles have a significantly lower risk of death (HR = 0.821, 95% CI, 0.785-0.858). Notably, the difference in risk between moderate air pollution and mortality risk remained insignificant (HR = 0.993, 95% CI, 0.945-1.044). High air pollution, on the other hand, was independently linked to increased mortality risk as compared to low air pollution (HR = 1.162, 95% CI, 1.124-1.201). The relationship between NOx, PM10, and PM2.5-10 and all-cause mortality was found to be nonlinear (p for nonlinearity < 0.05). Furthermore, no significant interaction was identified between lifestyle and air pollution with respect to all-cause mortality. CONCLUSIONS: Exposure to ambient air pollution elevated the likelihood of mortality from any cause, which was impacted by individual lifestyles. To alleviate this hazard, it is crucial for authorities to escalate environmental interventions, while individuals should proactively embrace and sustain healthy lifestyles.
Subject(s)
Air Pollution , Biological Specimen Banks , Life Style , Humans , United Kingdom/epidemiology , Male , Air Pollution/adverse effects , Air Pollution/analysis , Female , Middle Aged , Aged , Cohort Studies , Mortality/trends , Particulate Matter/analysis , Particulate Matter/adverse effects , Adult , Cause of Death , Air Pollutants/analysis , Air Pollutants/adverse effects , UK BiobankABSTRACT
Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.
Subject(s)
Biodiversity , Magnoliopsida , Phylogeny , China , Magnoliopsida/growth & development , Altitude , Geological Phenomena , EcosystemABSTRACT
Cetaceans play a pivotal role in maintaining the ecological equilibrium of ocean ecosystems. However, their populations are under global threat from environmental contaminants. Various high levels of endocrine-disrupting chemicals (EDCs) have been detected in cetaceans from the South China Sea, such as the Indo-Pacific humpback dolphins in the Pearl River Estuary (PRE), suggesting potential health risks, while the impacts of endocrine disruptors on the dolphin population remain unclear. This study aims to synthesize the population dynamics of the humpback dolphins in the PRE and their profiles of EDC contaminants from 2005 to 2019, investigating the potential role of EDCs in the population dynamics of humpback dolphins. Our comprehensive analysis indicates a sustained decline in the PRE humpback dolphin population, posing a significant risk of extinction. Variations in sex hormones induced by EDC exposure could potentially impact birth rates, further contributing to the population decline. Anthropogenic activities consistently emerge as the most significant stressor, ranking highest in importance. Conventional EDCs demonstrate more pronounced impacts on the population compared to emerging compounds. Among the conventional pollutants, DDTs take precedence, followed by zinc and chromium. The most impactful emerging EDCs are identified as alkylphenols. Notably, as the profile of EDCs changes, the significance of conventional pollutants may give way to emerging EDCs, presenting a continued challenge to the viability of the humpback dolphin population.
Subject(s)
Dolphins , Endocrine Disruptors , Population Dynamics , Animals , Endocrine Disruptors/toxicity , Water Pollutants, Chemical/toxicity , Environmental MonitoringABSTRACT
The use of healthcare products containing triclosan has surged globally due to the COVID-19 pandemic. In this study, we used a global spatially explicit model to simulate triclosan export by rivers to coastal seas in the post-COVID-19 era. The global triclosan model shows that the primary watersheds of triclosan export in Europe, Africa, Southeast Asia, United States, Brazil, India, and China, with river mouths presenting higher ecological risk distributed in Europe, South Asia, and America. It is estimated that triclosan concentrations in more than 77 % of global watersheds will be below the toxicity threshold by 2030 if the per capita use of triclosan is halved. Rather than completely restricting the use of triclosan, we should focus on integrating the effectiveness data of triclosan to develop recommendations for essential usage, substitutes, and wastewater treatment plants that minimize triclosan pollution in the post-COVID-19 era.
Subject(s)
COVID-19 , Rivers , Triclosan , Water Pollutants, Chemical , Triclosan/analysis , Rivers/chemistry , Water Pollutants, Chemical/analysis , Humans , Hygiene , Oceans and Seas , Environmental Monitoring , SARS-CoV-2ABSTRACT
Interstitial lung disease (ILD) can lead to lung cancer, which brings great challenges to differential diagnosis and comprehensive treatment. However, the clinical features of lung-dominant connective tissue disease (LD-CTD) related ILD combined with lung cancer has not been validated. We report the case of an 80-year-old woman with LD-CTD treated regularly with nintedanib who presented progressive dyspnoea and hypoxemia after recurrent viral infections. Her chest computed tomography (CT) showed aggravated interstitial fibrosis in both lower lungs with moderate right pleural effusion. Clinicians should be alert to lung cancer in patients who are experiencing poor responsiveness to treatment or acute progression of ILD. The available literatures about the differential diagnosis of clinical manifestations, imaging, treatment and prognosis of LD-CTD are reviewed and discussed in this study.
Subject(s)
Adenocarcinoma of Lung , Connective Tissue Diseases , Lung Diseases, Interstitial , Lung Neoplasms , Humans , Female , Aged, 80 and over , Follow-Up Studies , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Connective Tissue Diseases/complications , Connective Tissue Diseases/diagnosis , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiologyABSTRACT
The coronavirus disease 2019 (COVID-19) vaccination is the most effective way to prevent COVID-19. However, for chronic kidney disease patients on long-term dialysis, there is a lack of evidence regarding the efficacy and safety of the immune response to the vaccine. The present meta-analysis explores the efficacy and safety of COVID-19 vaccine in the immune response of patients with chronic kidney disease (CKD) undergoing dialysis. PubMed, Web of Science, Science Direct, and Cochrane Library databases were systematically searched from January 1, 2020, to December 31, 2022. Data analysis was performed using REVMAN 5.1s and Stata14 software. Baseline data and endpoint events were extracted, mainly including age, sex, dialysis vintage, body mass index (BMI), vaccine type and dose, history of COVID-19 infection, seropositivity rate, antibody titer, pain at injection site, headache and other safety events. The meta-analysis included 33 trials involving 81,348 patients. The immune efficacy of patients with CKD and dialysis was 80% (95 CI, 73-87%). The seropositivity rate of individuals without COVID-19 infection was 76.48% (3,824/5,000), while the seropositivity rate of individuals with COVID-19 infection was 80.82% (1,858/2,299). The standard mean difference of antibody titers in CKD and dialysis patients with or without COVID-19 infection was 27.73 (95% CI, -19.58-75.04). A total of nine studies reported the most common adverse events: Pain at the injection site, accounting for 18% (95 CI, 6-29%), followed by fatigue and headache, accounting for 8 (95 CI, 4-13%) and 6% (95 CI, 2-9%), respectively. COVID-19 vaccine benefitted patients with CKD undergoing dialysis with seropositivity rate ≥80%. Adverse events such as fatigue, headache, and pain at the injection site may occur after COVID-19 vaccination but the incidence is low.
ABSTRACT
AIMS: This study aimed to compare the clinical outcomes and safety of endovascular treatment (EVT) in patients with primary versus secondary medium vessel occlusion (MeVO). METHODS: From the endovascular treatment for acute ischemic stroke in the China registry, we collected consecutive patients with MeVO who received EVT. The primary endpoint was a good outcome, defined as a modified Rankin Scale (mRS) 0 to 2 at 90 days. RESULTS: 154 patients were enrolled in the final analysis, including 74 primary MeVO and 80 secondary MeVO. A good outcome at 90 days was achieved in 42 (56.8%) patients with primary MeVO and 33 (41.3%) patients with secondary MeVO. There was a higher probability of good outcomes in patients with the primary vs secondary MeVO (adjusted odds ratio, 2.16; 95% confidence interval, 1.04 to 4.46; p = 0.04). There were no significant differences in secondary and safety outcomes between MeVO groups. In the multivariable analysis, baseline ASPECTS (p = 0.001), final modified thrombolysis in cerebral infarction score (p = 0.01), and any ICH (p = 0.03) were significantly associated with good outcomes in primary MeVO patients, while baseline National Institutes of Health Stroke Scale (p = 0.002), groin puncture to recanalization time (p = 0.02), and early neurological improvement (p < 0.001) were factors associated with good outcome in secondary MeVO patients. CONCLUSION: In MeVO patients who received EVT, there was a higher likelihood of poor outcomes in patients with secondary versus primary MeVO.
Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , United States , Humans , Stroke/surgery , Stroke/etiology , Brain Ischemia/surgery , Brain Ischemia/etiology , Treatment OutcomeABSTRACT
As long-lived apex predators, marine mammal adults often accumulate alarmingly levels of environmental contaminants. Nevertheless, the accumulation and risks of these contaminants in the critical calf stage of marine mammals remain largely unknown. Here, we investigated the exposure status and health risks of 74 organohalogen contaminants (OHCs) in Indo-Pacific humpback dolphin calves (Sousa chinensis) collected from the Pearl River Estuary (PRE), China, during 2005-2019. Our findings revealed moderate levels of polychlorinated biphenyls (PCBs), medium-high levels of dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs), and the highest levels of polybrominated diphenyl ethers (PBDEs) and alternative halogenated flame retardants (AHFRs) compared to those reported for cetaceans elsewhere. Traditional OHCs like DDTs, PCBs, and PBDEs did not exhibit significant decreasing trends in the dolphin calves despite global restrictions on these compounds, and AHFRs as emerging OHCs showed an increasing trend over the study period. Risk quotients of DDTs, HCHs, PBDEs, and PCBs in most of the dolphin samples were > 1, indicating that humpback dolphin calves may have suffered long-term threats from OHC exposure. The significant correlation observed between the traditional OHC levels and the stranding death number of the dolphin calves suggests these OHCs may impact the survival of this endangered species.
Subject(s)
Dolphins , Polychlorinated Biphenyls , Animals , Polychlorinated Biphenyls/analysis , Halogenated Diphenyl Ethers/toxicity , Environmental Monitoring , Hexachlorocyclohexane , EcosystemABSTRACT
OBJECTIVE: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER: NCT03633617.
Subject(s)
Deglutition Disorders , Eosinophilic Esophagitis , Adolescent , Adult , Humans , Antibodies, Monoclonal, Humanized/adverse effects , Deglutition Disorders/etiology , Deglutition Disorders/drug therapy , Double-Blind Method , Endoscopy , Eosinophilic Esophagitis/drug therapy , Glucocorticoids/therapeutic use , Treatment OutcomeABSTRACT
Cadmium (Cd) pollution is a public environmental problem worthy of attention. Long-term exposure to Cd may have adverse effects on human health. Our previous study showed that urinary concentration of Cd (U-Cd) in the residents decreased when Cd-polluted paddy soil was removed. However, from 2008 to 2014, the concentration of U-Cd increased. At the same time, the concentration of urinary ß2-microglobulin (ß2-MG), which is considered to be an early sign of cadmium-induced renal dysfunction, increased continuously. To find the cause of elevated urinary cadmium (U-Cd) in residents of cadmium-contaminated areas, we measured the concentration of cadmium in the blood (B-Cd) of 29 elderly residents (15 female and 14 male) and edible rice (R-Cd), and correlations between R-Cd, B-Cd, and U-Cd were analyzed in the formerly cadmium-polluted areas (the Kakehashi River basin). In 2016, we collected blood, urine, and rice samples from each participant. The analysis showed a significant correlation between age and B-Cd, U-Cd, and ß2-MG. However, there was no significant correlation between R-Cd and U-Cd, B-Cd, or ß2-MG concentrations. Although we found a slightly higher level of Cd in rice and urine than reported in 2008, we cannot be sure that it indicates an increased Cd contamination in the Kakehashi River basin because larger studies are required for such a conclusion. The increased urinary Cd concentrations in this area may be because Cd in tissues and organs returns to blood and urine as participants age, which leads to an increasing trend.
Subject(s)
Cadmium , Oryza , Humans , Male , Female , Aged , Cadmium/analysis , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Rivers , Environmental Pollution/adverse effects , Environmental Pollution/analysis , beta 2-Microglobulin/urine , JapanABSTRACT
The detrimental effects of bisphenol (BP) exposure are a concern for vulnerable species, Indo-Pacific humpback dolphins (Sousa chinensis). To investigate the characteristics of BP profiles and their adverse impact on humpback dolphins, we assessed the concentrations of six BPs, including bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), bisphenol B (BPB), and bisphenol P (BPP) in blubber (n = 26) and kidney (n = 12) of humpback dolphins stranded in the Pearl River Estuary, China. BPS accounted for the largest proportion of the total bisphenols (∑BPs) in blubber (55%) and kidney (69%). The concentration of ∑BP in blubber was significantly higher than that in the kidney and liver. The EC50 values of five BPA alternatives were lower than those of BPA in humpback dolphin skin fibroblasts (ScSF) and human skin fibroblasts (HSF). ScSF was more sensitive to BPS, BPAF, BPB, and BPP than HSF. The enrichment pathway of BPA was found to be associated with inflammation and immune dysregulation, while BPP and BPS demonstrated a preference for genotoxicity. BPA, BPP, and BPS, which had risk quotients (RQs) > 1, were found to contribute to subhealth and chronic disease in humpback dolphins. According to the EC50-based risk assessment, BPS poses a higher health risk than BPA for humpback dolphins. This study successfully evaluated the risks of bisphenols in rare and endangered cetacean cell lines using a noninvasive method. More in vivo and in field observations are necessary to know whether the BPA alternatives are likely to be regrettable substitutions.
Subject(s)
Dolphins , Water Pollutants, Chemical , Animals , Humans , Dolphins/metabolism , Water Pollutants, Chemical/toxicity , China , Benzhydryl Compounds/toxicityABSTRACT
Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.
Subject(s)
Gastrointestinal Microbiome , Intestinal Diseases , Humans , Fecal Microbiota Transplantation/methods , Gastrointestinal Microbiome/physiology , Housing , Intestinal Diseases/drug therapyABSTRACT
BACKGROUND: Eosinophilic esophagitis (EoE) has a detrimental effect on health-related quality of life (HRQOL). The Eosinophilic Esophagitis Impact Questionnaire (EoE-IQ) is a novel patient-reported outcome (PRO) measure assessing the impact of EoE on HRQOL. To assess suitability of the EoE-IQ, its measurement properties were evaluated. METHODS: Using baseline and week 24 data from the pivotal, randomized, placebo-controlled, multinational phase 3 R668-EE-1774 trial (NCT03633617) of dupilumab, we evaluated EoE-IQ's measurement properties (including reliability, construct and known-groups validity, and ability to detect change) and established the threshold for change in scores that can be considered clinically meaningful. RESULTS: The analysis population comprised 239 adults and adolescents with EoE. Mean age was 28.1 (standard deviation, 13.14) years; 63.6% were male, and 90.4% were White. Reliability estimates for the EoE-IQ average score exceeded acceptable thresholds for patients who were stable as indicated by ratings of Patient Global Impression of Severity (PGIS) and Change (PGIC) (intraclass correlation coefficients, 0.75 and 0.81). Construct validity correlations with other EoE-specific PRO scores were moderate at baseline (|r|= 0.44-0.60) and moderate to strong at week 24 (|r|= 0.61-0.72). In known-groups analysis, EoE-IQ average score discriminated among groups of patients at varying EoE severity levels defined by PGIS scores. A ≥ 0.6-point reduction in EoE-IQ average score (where scores range from 1 to 5, with higher scores indicating worse HRQOL) from baseline to week 24 can be considered clinically meaningful. CONCLUSIONS: The EoE-IQ's measurement properties are acceptable, making it a valid, reliable measure of the HRQOL impacts of EoE among adults and adolescents. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03633617. Registered August 14, 2018, https://clinicaltrials.gov/study/NCT03633617 .
Subject(s)
Eosinophilic Esophagitis , Adolescent , Adult , Female , Humans , Male , Eosinophilic Esophagitis/diagnosis , Quality of Life , Reproducibility of Results , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
IMPORTANCE: Flagellar motility plays an important role in the environmental adaptation of bacteria and is found in more than 50% of known bacterial species. However, this important characteristic is sparsely distributed within members of the phylum Actinobacteria, which constitutes one of the largest bacterial groups. It is unclear why this important fitness organelle is absent in most actinobacterial species and the origin of flagellar genes in other species. Here, we present detailed analyses of the evolution of flagellar genes in Actinobacteria, in conjunction with the ecological distribution and cell biological features of major actinobacterial lineages, and the co-evolution of signal transduction systems. The results presented in addition to clarifying the puzzle of sporadic distribution of flagellar motility in Actinobacteria, also provide important insights into the evolution of major lineages within this phylum.
ABSTRACT
Bloodstream infection (BSI) caused by bacteria is highly pathogenic and lethal, and easily develops whole-body inflammatory state. Immediate identification of disease-causing bacteria can improve patient prognosis. Traditional testing methods are not only time-consuming, but such tests are limited to laboratories. Recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) holds great promise for rapid nucleic acid detection, but the uncapping operation after amplification easily contaminates laboratories. Therefore, the establishment of a more effective integrated isothermal amplification system has become an urgent problem to be solved. In this study, we designed and fabricated a hermetically sealed integrated isothermal amplification system. Combining with this system, a set of RPA-LFD assays for detecting S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI were established and evaluated. The whole process could be completed in less than 15 min and the results can be visualized by the naked eye. The developed RPA-LFD assays displayed a good sensitivity, and no cross-reactivity was observed in seven similar bacterial genera. The results obtained with 60 clinical samples indicated that the developed RPA-LFD assays had high specifcity and sensitivity for identifying S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI. In conclusion, our results showed that the developed RPA-LFD assay is an alternative to existing PCR-based methods for detection of S. aureus, K. peneumoniae, P. aeruginosa, and H. influenza in BSI in primary hospitals.