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Background: Intervertebral disc degeneration (IVDD) stands as a primary pathophysiological driver of low back pain, yet no therapeutic intervention effectively arrests its progression. Evidence shows that certain Sirt1 agonists may confer protective effects on intervertebral discs, but the underlying mechanisms remain unclear. This study aims to delineate the interaction between Sirt1 and the inflammatory microenvironment, offering potential novel avenues for IVDD prevention and treatment., Methods: In vitro IL-1β-induced nucleus pulposus cells (NPCs) degenerative model and in vivo a mouse annulus fibrosus needle puncture model in Sirt1 transgenic (Sirt1 TG ) and the same litter WT mice were used to investigate the role of Sirt1 in homeostasis and inflammation. Mechanistic insights were obtained through RNA sequencing, co-immunoprecipitation (Co-IP), luciferase assays, and chromatin immunoprecipitation-(ChIP)-PCR. A co-culture system of Raw264.7 and NPCs was employed to assess the involvement of Lipocalin 2., Results: Our study demonstrated reduced Sirt1 expression in degenerating human nucleus pulposus (NP) tissue. Both in vitro and in vivo data revealed that NP-specific overexpression of Sirt1 inhibited extracellular matrix degradation and inflammation. Mechanistically, Sirt1 suppressed the acetylation of RelA/p65 at lysine 310 and phosphorylation at serine 536, with the C-terminus of Sirt1 and the RHD-NLS domain of RelA mediating to their interaction. Furthermore, NPCs-derived Lipocalin 2 was identified as a cytokine involved in macrophage chemotaxis and M1 polarization to exacerbate inflammation., Conclusion: Our work revealed that Sirt1 negatively regulates Lipocalin 2, thereby ameliorating the inflammatory milieu and blocking NPCs and macrophages crosstalk., The Translational Potential of This Article: This study illuminates the crucial role and molecular mechanisms of Sirt1 in regulating the NP microenvironment. These insights shed light on strategies for the prevention and treatment of IVDD-related herniation and low back pain. By pinpointing specific biological targets, the screening of smallmolecule compounds with significant clinical implications can be facilitated. This translational innovation promises to optimize cells communication within intervertebral disc microenvironment via localized drug delivery, potentially improving patient outcomes and satisfaction following spinal fusion or discectomy surgeries., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis., Objective: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC)., Methods: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models., Results: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures., Conclusions: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions., Methods: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales., Results: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006)., Conclusions: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality., Methods: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries., Results: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68)., Conclusions: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals., Impact and Implications: While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated., Methods: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817)., Results: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence., Conclusion: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer., Methods: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ 2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing., Findings: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis., Interpretation: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer., Funding: Ministry of Health and Welfare of Taiwan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Teeth are one of the body tissues remaining after severe decomposition from which a DNA profile can be obtained to aid in human identification. Currently, the standard approach to isolate DNA from teeth requires pulverizing the entire tooth. This destructive approach compromises any further morphological or anthropological study. We report on two methods of DNA isolation that minimizes destruction of the tooth when accessing the DNA within pulp and cementum. Forty-nine teeth, removed as part of normal dental procedures, were buried for up to 92 days, with a further nine teeth acting as unburied controls. Additionally, four teeth samples collected during a forensic examination were included in this study. The two processes were: using a fine drill to access the pulp from the crown and then using endodontic files to collect the biological material; and using a sterile blade to scrape the cementum. It was found that the samples collected from the cementum had greater DNA quality compared to those samples obtained from the pulp. Microbial activity was found to play a role in the degradation of the nuclear material, reducing DNA yields from pulp. DNA profiling data from 24 loci, including 22 STR markers, indicated that multi-rooted teeth provided better DNA quantity and quality than those with a single root. The DNA quantity obtained from pulp samples of teeth which exhibited cavities was adversely affected, although this DNA loss was not from samples collected from the cementum of teeth in similar condition. Obtaining samples from DNA profiling from the cementum was found to be ideal if the morphological preservation of the tooth is required. Obtaining pathogen DNA is of interest when an occlusal approach to retrieve pulp may serve as a good alternative to prepare DNA without destruction of the tooth structure., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Evidence of the association between particles with a diameter of 2.5 μm or less (PM 2.5 ) in long term and ovarian cancer (OC) mortality is limited., Methods: This prospective cohort study analyzed data collected between 2015 and 2020 from 610 newly diagnosed OC patients, aged 18-79 years. The residential average PM 2.5 concentrations 10 years before the date of OC diagnosis were assessed by random forest models at a 1 km × 1 km resolution. Cox proportional hazard models fully adjusted for the covariates (including age at diagnosis, education, physical activity, kitchen ventilation, FIGO stage, and comorbidities) and distributed lag non-linear models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of PM 2.5 and all-cause mortality of OC., Results: During a median follow-up of 37.6 months (interquartile: 24.8-50.5 months), 118 (19.34 %) deaths were confirmed among 610 OC patients. One-year PM 2.5 exposure levels before OC diagnosis was significantly associated with an increase in all-cause mortality among OC patients (single-pollutant model: HR = 1.22, 95 % CI: 1.02-1.46; multi-pollutant models: HR = 1.38, 95 % CI: 1.10-1.72). Furthermore, during 1 to 10 years prior to diagnosis, the lag-specific effect of long-term PM 2.5 exposure on the all-cause mortality of OC had a risk increase for lag 1-6 years, and the exposure-response relationship was linear. Of note, significant interactions between several immunological indicators as well as solid fuel use for cooking and ambient PM 2.5 concentrations were observed., Conclusion: Higher ambient PM 2.5 concentrations were associated with an increased risk of all-cause mortality among OC patients, and there was a lag effect in long-term PM 2.5 exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Emerging evidence supports shifting the focus from the quantity of macronutrients to quality to obtain greater benefits for the prognosis of ovarian cancer (OC). Additionally, despite the high relevance between macronutrient quality and quantity, the interaction of these parameters on OC survival remains unknown., Objective: A multidimensional macronutrient quality index (MQI) was applied to investigate the association between overall macronutrient quality and the survival of patients with OC., Methods: A prospective cohort study was conducted with 701 females diagnosed with OC who were enrolled from 2015 to 2020. Dietary intake information was obtained from a validated food frequency questionnaire. The MQI was calculated based on 3 quality indices: carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Cox proportional hazards regression was conducted to calculate HRs and 95% CIs. Furthermore, we evaluated whether energy intake status (total energy intake and energy balance) modified the association between MQI and OC survival., Results: During a median follow-up period of 38 (interquartile: 35-40) mo, 130 deaths occurred. The prediagnosis high MQI scores were associated with substantially improved survival among females with OC (HR tertile 3 vs. tertile 1 = 0.50, 95% CI: 0.33, 0.77). For sub-indices of the MQI, higher CQI (HR = 0.60, 95% CI: 0.36, 0.99), higher FQI (HR = 0.55, 95% CI: 0.34, 0.87), and higher PQI (HR = 0.58, 95% CI: 0.35, 0.94) scores were all associated with better survival. Notably, significant interactions were observed for the MQI score with total energy intake and energy balance as well as the quantity and quality of carbohydrates on survival., Conclusions: Intake of high-quality macronutrients before diagnosis was associated with improved survival among females with OC, especially for those with energy imbalance., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used to treat advanced non-small cell lung cancer (NSCLC). A rapid and reliable method for measuring plasma and cerebrospinal fluid (CSF) concentrations of EGFR-TKIs is needed for therapeutic drug monitoring. By using UHPLC‒MS/MS with multiple reaction monitoring mode, we developed a method for rapidly determining the plasma and CSF concentrations of gefitinib, erlotinib, afatinib, and osimertinib. Protein precipitation was employed to remove protein interference for plasma and CSF matrix. The LC‒MS/MS assay was validated to be satisfactory in terms of linearity, precision, and accuracy. This method was successfully applied to measure plasma (n = 44) and CSF (n = 6) concentrations of EGFR-TKIs in NSCLC patients. The chromatographic separation was achieved by a Hypersil Gold aQ column within 3 min. The median plasma concentrations were 325.76, 1981.50, 42.62, 40.27, and 340.92 ng/ml for gefitinib erlotinib, afatinib 30 mg/day, afatinib 40 mg/day, and osimertinib, respectively. The CSF penetration rates were 2.15% for the patients receiving erlotinib therapy, 0.59% for afatinib, 0.08-1.12% for osimertinib 80 mg/day, and 2.18% for those receiving osimertinib 160 mg/day. This assay helps to predict the effectiveness and toxicities of EGFR-TKIs in the pursuit of precision medicine for lung cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recent evidence advises particles with a diameter of 2.5 µm or less (PM 2.5 ) might be a prognostic factor for ovarian cancer (OC) survival. The oxidative balance score (OBS) incorporates diet-lifestyle factors to estimate individuals' anti-oxidant exposure status which may be relevant to cancer prognosis. We aimed to investigate the roles of PM 2.5 , and OBS and their interaction in OC prognosis. 663 patients with OC were enrolled in the current study. Satellite-derived annual average exposures to PM 2.5 based on patients' residential locations. The OBS was calculated based on 16 different diet-lifestyle components derived using an acknowledged self-reported questionnaire. The Cox regression model was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also assessed the effect of modification between PM 2.5 and OS by OBS via interaction terms. During a median follow-up of 37.57 (interquartile:35.27-40.17) months, 123 patients died. Compared to low-concentration PM 2.5 exposure, high PM 2.5 during 1 year before diagnosis was associated with worse OC survival (HR= 1.19, 95% CI = 1.01-1.42). We observed an improved OS with the highest compared with the lowest OBS (HR = 0.46, 95% CI = 0.27-0.79, P for trend < 0.05). Notably, we also found an additive interaction between low OBS and high exposure to PM 2.5 , with the corresponding associations of PM 2.5 being more pronounced among participants with lower OBS (HR = 1.42, 95% CI = 1.09-1.86). PM 2.5 may blunt OC survival, but high OBS represented an antioxidative performance that could alleviate the adverse association of PM 2.5 and OS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear., Methods: We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3., Results: Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693-2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533-2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415-1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970-1.206; p = 0.160)., Conclusions: The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypochlorous acid/hypochlorite (HOCl/ClO - ) plays important roles in killing bacterial and causing damage to living tissues, and its abnormal levels could lead to many diseases. Although great efforts have been devoted, fluorescent probes for HOCl/ClO - with near-infrared fluorescence, good selectivity/sensitivity, and low background are still important and urgent. In this work, a novel double-bond-linked TCF-aza-BODIPY-based near-infrared fluorescent probe (3) was rationally designed, successfully prepared, and applied for sensing HOCl/ClO - in both solutions and living RAW264.7 cells, showing good selectivity and fluorescence "turn-on" phenomenon at 670 nm with low background. The limit of detection towards ClO - was determined to be 0.36 μM through the linear fluorescence changes at 670 nm in a broad ClO - -concentration range of 0-150 μM. Furthermore, the sensing mechanism was investigated by mass spectrometry and compared with 1, suggesting that the remarkable spectroscopic changes could be ascribed to the oxidization of the double bond to the aldehyde group, accompanied with the leaving of the TCF group. Confocal imaging experiments also confirmed the remarkable intracellular fluorescence enhancements through incubation of ClO - and phorbol ester 12-myristate 13-acetate (PMA) in RAW264.7 cells. Therefore, for the first time, we reported a near-infrared TCF-aza-BODIPY-based fluorescent probe for highly sensitive and fluorescence "turn-on" detection of both exogenous and endogenous HOCl in living RAW264.7 cells through the quick oxidation of a conjugated double bond., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Evidence for a role of single nutrition or foods on ovarian cancer (OC) survival has been limited and inconclusive. Due to the potentially complex interactions in dietary, we applied dietary patterns to this study to firstly explore the relationship between the pre-diagnosis overall diet and OC survival., Methods: The prospective cohort study was conducted among 853 OC patients aged 18-79 years during 2015-2020. Dietary intake was collected using a validated 111-item food frequency questionnaire. Deaths were obtained by medical records and cancer registry up to March 31, 2021. Cox proportional hazards regression models was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of pre-diagnosis dietary patterns with overall survival (OS)., Results: Overall, during the follow-up period (median: 37.57 months, interquartile: 25.00-50.17 months), 130 (18.49%) OC patients died. Four dietary patterns were identified: healthy pattern, ethnic pattern, animal foods pattern, and sweet pattern. The highest tertile of the healthy pattern scores was related to better OS compared with the lowest tertile scores (HR = 0.54, 95% CI = 0.30-0.98, p trend <0.05), whereas OC patients with highest adherence to the animal foods pattern was associated with worse OS than those with the lowest adherence (HR = 1.90, 95% CI = 1.14-3.17, p trend <0.05). We found no significant associations between adherence to ethnic pattern and sweet pattern and OS of OC patients., Conclusion: Pre-diagnosis healthy patterns was associated with better OC survival, whereas animal pattern was associated with worse survival among OC survivals., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

A novel near-infrared-emitting aza-BODIPY-based fluorescent probe with two tellurium atoms at two upper benzyl rings has been prepared and explored for its fluorescent sensing properties towards hypochlorous acid/hypochorite (HClO/ClO - ), which showed high selectivity and absolutely fluorescent "turn-on" phenomenon at 738 nm. The fluorescence of this probe was sufficiently quenched due to photoindued electron transfer by two tellurium atoms. Upon exposure to HClO/ClO - , a strong near-infrared emission at 738 nm appeared with fluorescence quantum yields changing from 0 to 0.11. This remarkable fluorescence change was ascribed to the oxidation of both electron-rich tellurium atoms. The detection limit of this probe towards HClO/ClO - was calculated to 0.09 μM in acetonitrile aqueous solution by the linear fluorescence change at 738 nm in the HClO/ClO - -concentration range of 0-30 μM. Interestingly, this probe was found to be applicable in a broad pH range (2-10). Meanwhile, the oxidized probe could be further responsive to biothiols with substantial fluorescence disappearance. The bioimaging experiments in RAW264.7 cells showed the appearance of intracellular near-infrared fluorescence after addition of HClO/ClO - and PMA, and the fluorescence could also be reversed to be silenced by further introduction of GSH, confirming its potential application for exogenous and endogenous detection of HClO/ClO - in living cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new near-infrared (NIR)-emitting aza-boron-dipyrromethene dye with two electron-donating amino groups at 1- and 7-positions has been prepared via several steps of reactions. This probe showed a NIR absorption at 748 nm with an obvious shoulder peak at 634 nm in CH 3 CN/H 2 O. Interestingly, a NIR fluorescence emission at 843 nm was observed with a large Stokes shift of 95 nm. This novel NIR-emitting aza-boron-dipyrromethene dye was further investigated as a Hg 2+ -sensing fluorescent probe, which selectively bound to Hg 2+ , showing a blue-shifted and sharp absorption band at 695 nm with the disappearance of the shoulder peak at 634 nm. Correspondingly, the color change could be easily seen from blue to green. Interestingly, the emission exhibited an absolutely "turn-on" peak at 725 nm with a significant blue shift by 118 nm (from 843 to 725 nm), due to the efficient inhibition of the intramolecular-charge-transfer process arising from two amino groups. This probe was finally introduced to Hela cells, showing a "OFF-ON" NIR emission upon exposure to Hg 2+ . The overall results confirmed that this novel NIR-emitting aza-boron-dipyrromethene fluorescent probe with a large Stokes shift could serve as a colorimetric and fluorescent "turn-on" sensor for Hg 2+ in both solutions and living cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Two probes based on tetrahydroxanthylium unit (probe 1a) and methyltetrahydroxanthylium unit (probe 1b) were designed and synthesized for the detection of hydrazine. Probes 1a-b exhibited turn-on red emission signal and high selectivity toward NH 2 NH 2 . The response time of probe 1a to NH 2 NH 2 was more than 60 min, while that of probe 1b was less than 30 min. The detection limits of probes 1a-b were calculated as 210 nM and 110 nM respectively. What's more, the tolerance experiments showed that methyltetrahydroxanthylium unit possessed higher tolerance toward nucleophiles. Moreover, cells imaging experiments demonstrated that probe 1b could detect exogenous NH 2 NH 2 in living HeLa cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Mycobacterium avium complex-lung disease (MAC-LD) is increasing worldwide and may progress to cause mortality significantly. However, for patients without initial treatment at diagnosis, the survival outcomes and predictors of mortality remain unclear., Methods: From 2011 to 2017, MAC-LD patients at two medical centers in Taiwan were screened, and those who received MAC treatment at the initial were excluded. The clinical course and characteristics were recorded. Cox regression analysis and receiver operating characteristic (ROC) curves were performed to assess risk factors of mortality within 4 years., Results: We included 123 MAC-LD patients without initial MAC treatment. The mean follow-up period was 4.15 ± 2.52 years. Twenty-two (17.9%) patients died within four years. Multivariate analysis showed that four independent factors related to 4-year mortality were consolidation pattern (hazard ratio [HR] 6.0, 95% confidence interval [2.3-15.5]), radiographic score > 6 (HR:11.0 [4.0-31.1]), radiographic deterioration within two years (HR: 5.2 [2.1-13.1]) and no MAC treatment during follow up (HR: 6.5 [1.3-31.1]). The areas under the ROC curves for prediction of 4-year mortality for the combination of consolidation and radiographic score >6, the two factors plus radiographic progression, the two plus no MAC treatment, and the combination of the four factors were 0.702, 0.798, 0.758, and 0.835, respectively., Conclusions: The four-year mortality rate in MAC-LD without initial treatment is high. Presence of consolidation pattern and radiographic score >6 at initial visit, radiographic deterioration and no treatment during follow-up were risk factors of 4-year mortality in initially untreated MAC-LD., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The detection and treatment of latent tuberculosis infection (LTBI) is a key step in eliminating tuberculosis (TB), but information on safety and on treatment interruption in elderly LTBI patients remains limited., Methods: This multicenter prospective observational study included individuals with LTBI who underwent preventive therapy. Incidents of systemic adverse reactions (SARs) and treatment interruption rates in an elderly group (≥60 years old) and a young group (<60 years old) were analyzed., Results: A total of 406 LTBI patients, comprising 167 elderly and 239 young patients, were included in the analyses. The incidence of SARs was similar in the elderly group (18%) and the young group (15.1%). Being middle-aged (35-59 years), body mass index <23 kg/m 2 , a regimen of 3 months of once-weekly rifapentine plus isoniazid, and end-stage renal disease were independent factors associated with SARs. The treatment interruption rate was similar between the elderly group (21.6%) and the young group (15.9%). LTBI patients aged ≥80 years with SARs had the highest risk of treatment interruption., Conclusions: The occurrence of SARs was similar in the elderly (≥60 years old) and young (<60 years old) LTBI patients receiving preventive therapy. Extremely old (≥80 years old) LTBI patients had a higher treatment interruption rate, especially when they had SARs., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A small molecule fluorescent probe (probe 1) based on adenine-coumarin derivative was designed and synthesized in this paper. Probe 1 exhibited a significant fluorescence-enhancing response to nucleic acids at 495 nm (for DNA) and 487 nm (for RNA). The fluorescence enhancement of probe 1 for DNA and RNA was 5.68 and 9.73 times respectively, the fluorescence quantum yield was changed from 2.5% to 11.7% and 22.5% accordingly. Meanwhile, an excellent linear relationship of fluorescence intensity at 495 nm or 487 nm versus the nucleic acid concentration (1 μM for probe 1, 0-350 μg/mL for DNA and 0-300 μg/mL for RNA) was obtained. Co-staining and nucleic acid digestion experiments showed that probe 1 could selectively image nucleic acids in mitochondria and nucleoli in HeLa cells., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: Osimertinib is a third-generation EGFR-tyrosine kinase inhibitor (TKI). Durvalumab is an anti-programmed death ligand 1 monoclonal antibody. The phase III open-label CAURAL trial (NCT02454933) investigated osimertinib plus durvalumab versus osimertinib monotherapy in patients with EGFR-TKI sensitizing and EGFR T790M mutation-positive advanced NSCLC and disease progression after EGFR-TKI therapy., Methods: Patients were randomly assigned 1:1 to receive orally administered osimertinib (80 mg once daily) with or without durvalumab (10 mg/kg administered intravenously every 2 weeks) until progression. Treatment could continue beyond progression, providing clinical benefit continued (judged by the investigator). The amended primary objective was to assess the safety and tolerability of osimertinib plus durvalumab; efficacy was an exploratory objective., Results: CAURAL recruitment was terminated early because of increased incidence of interstitial lung disease-like events in the osimertinib plus durvalumab arm from the separate phase Ib TATTON trial (NCT02143466). At termination of CAURAL recruitment, 15 patients had been randomly assigned to treatment with osimertinib and 14 to treatment with osimertinib plus durvalumab. The most common AEs were diarrhea (53% [grade ≥3 in 6% of patients]) in the osimertinib arm and rash (67% [grade ≥3 in 0 patients]) in the combination arm. One patient who had been randomized to the combination arm reported grade 2 interstitial lung disease while receiving osimertinib monotherapy (after discontinuing durvalumab therapy after one dose). The objective response rates were 80% in the osimertinib arm and 64% in the combination arm., Conclusion: Limited patient numbers preclude formal safety and efficacy comparisons between the two treatment arms. The combination of programmed cell death 1/programmed death ligand 1 inhibitors and EGFR-TKIs as therapy for NSCLC is not well understood, but it requires a careful approach if considered in the future., (Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: As the first-line treatment, afatinib is commonly used in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, dose adjustments are frequently required. The optimal dose of afatinib for brain metastasis has seldom been investigated., Patients and Methods: From May 2014 to March 2017, treatment-naive patients with advanced EGFR-mutated NSCLC and brain metastases at diagnosis who received afatinib therapy were retrospectively enrolled. Clinical data was reviewed and analyzed, including age, gender, performance status, smoking history, EGFR mutation status, initial doses of afatinib, average daily doses of afatinib, and best intracranial treatment responses., Results: A total of 74 patients were included for analysis. The overall intracranial objective response rate (IORR) and intracranial disease control rate (IDCR) were 81.1% and 95.9%, respectively. For patients treated with afatinib alone (N = 45), no significant difference between an initial daily dose of 30 mg (N = 15) and 40 mg (N = 30) (30 mg vs. 40 mg, IORR: 86.7% vs. 80.0%; P = .581 and IDCR: 93.3% vs. 93.3%; P = 1.000, respectively). The IORRs were 75.0%, 91.7%, 80.0%, and 85.7% (P = .707), and the IDCRs were 93.8%, 100.0%, 90.0%, and 85.7% (P = .638) in patients with an average daily dose of 40 mg (N = 16), < 40 mg and > 30 mg (N = 12), 30 mg (N = 10), and < 30 mg and > 20 mg (N = 7), respectively. No significant differences in intracranial treatment responses between groups treated with afatinib alone or afatinib plus local treatments., Conclusion: Dose reduction may not affect intracranial treatment responses to afatinib therapy, either alone or combined with local treatments, in patients with advanced EGFR-mutated NSCLC and brain metastases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Several modeling approaches have been developed for simulating ambient PAHs, but no hourly intra-urban spatial data are currently available. The aim of this study is to develop a new modeling strategy in simulating, on an hourly basis, grid-scale PM2.5-PAH levels. PM and PAHs were collected over a one-year time frame through an established air quality monitoring network within a metropolitan area of Taiwan. Multivariate linear regression models, in combination with correlation analysis and PAH source identification by principal component analysis (PCA), were performed to simulate hourly grid-scale PM2.5-PAH concentrations, taking criteria pollutants and meteorological variables selected as possible predictors. The simulated levels of 72-h personal exposure were found to be significantly (R=0.729**, p<0.01) correlated with those analyzed from portable personal monitors. A geographic information system (GIS) was used to visualize spatially distributed PM2.5-PAH concentrations of the modeling results. This new grid-scale modeling strategy, incorporating the output of simulated data by GIS, provides a useful and versatile tool in personal exposure analysis and in the health risk assessment of air pollution., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Various metal transporters mediate sub-cellular sequestration of diverse metal ions, contribute to cellular metal tolerance, and control metal partitioning, particularly under conditions of high rates of metal influx into organisms. In the current study, a ubiquitous and evolutionary conserved metal transporter gene, homology to natural resistance associated macrophage protein (Nramp), was cloned from a metal-tolerant isolate of dark septate endophyte (DSE, Exophiala pisciphila), and its functional and transcript characterization were analyzed. The full-length Nramp gene from E. pisciphila (named EpNramp) was 1716 bp and expected to encode a polypeptide of 571 amino acid residues. EpNramp fused to green fluorescent protein suggested that EpNramp was a plasma membrane metal transporter, which was consistent with the results of bioinformatics analysis with 11 transmembrane domains. Yeast functional complementation revealed that EpNramp could complement the growth defect of Fe-uptake yeast mutant (fet3fet4 double mutant) by mediating the transport of Fe(2+). Expression of EpNramp increased Cd(2+) sensitivity and Cd(2+) accumulation in yeast. In addition, qPCR data revealed that E. pisciphila significantly down-regulated EpNramp expression with elevated Cd(2+) exposure. Altogether, EpNramp is a bivalent cation transporter localized in cell membrane, which is necessary for efficient translocation of both Fe and Cd, and its activities partly attributed to the tolerance of DSE to toxic and excessive Cd(2+) supplements., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment., Method: A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290., Results: A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up., Conclusions: In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.

Background: Ethnic differences exist in the function and distribution of adipose tissue, which influences whole body metabolism, including pulmonary function. The object of this study was to examine the relationships between serum metabolic parameters and pulmonary function in a morbidly obese Asia-Pacific population., Methods: One-hundred thirty-seven morbidly obese Chinese patients, aged≥18 years with a body mass index (BMI)>32 kg/m(2) who were being evaluated for bariatric surgery between July 2007 and December 2008, were studied. Cross-sectional associations between serum metabolic parameters, including lipids, glucose, insulin, leptin, and adiponectin levels with forced vital capacity (FVC) and forced expiratory volume in the first second (FEV₁) assessed by spirometry, were analyzed. Multiple regression analyses also were conducted, with age, gender, smoking history, and various anthropometric measurements of obesity as confounders., Results: Serum adiponectin and HDL cholesterol had a positive correlation with FVC and FEV1. In addition, insulin resistance, determined by the homeostatic model assessment method (HOMA), was negatively correlated with FVC. In the multiple linear regression analysis, only serum adiponectin was significantly correlated with FVC and FEV₁, independent of obesity level., Conclusions: Serum adiponectin level was positively and independently associated with pulmonary function in morbidly obese Chinese adults., (Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is associated with impaired pulmonary function. We evaluated the effect of bariatric surgery on pulmonary function among obese patients and identified potential anthropometric factors of obesity corresponding to the reversal of impaired pulmonary function., Methods: Pulmonary function and anthropometric factors were studied in 94 obese patients aged 18-65 years with a body mass index >32 kg/m(2). Pulmonary function tests were performed preoperatively and 3 months after bariatric surgery. The measurements included forced vital capacity (FVC), forced expiratory volume in the first second (FEV(1)), total lung capacity, expiratory reserve volume, residual volume, and diffusing capacity of the lung for carbon monoxide. The anthropometric factors included the body weight, body mass index, waist circumference (WC), hip circumference, waist/height ratio, and waist/hip ratio. The changes in anthropometric parameters were analyzed in relation to pulmonary function test results. Multiple linear regression models were applied to identify the factors that influenced pulmonary function after bariatric surgery., Results: When measured 3 months after surgery, all anthropometric parameters for the 94 patients studied had significantly decreased, and the pulmonary function test parameters had significantly improved. Of the anthropometric parameters, the reduction in body weight, WC, and waist/height ratio correlated significantly with increases in the FEV(1) and FVC. In the multiple linear regression analysis, only the reduction in WC correlated significantly with the reductions in the FEV(1) and FVC., Conclusion: After bariatric surgery, all anthropometric parameters of obesity decreased significantly and the pulmonary function improved. This improvement correlated best with the reduction in the WC and perhaps a decreased intra-abdominal pressure., (Copyright © 2011 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

A DNA-intercalating Ru(II) polypyridyl complex [Ru(bpy)2(appo)]2+ (bpy=2,2'-bipyridine, appo=11-aminopteridino[6,7-f][1,10]phenanthrolin-13(12H)-one) has been synthesized and characterized by elemental analysis, electrospray mass spectra, (1)H NMR, UV/Vis spectrum, fluorescent spectrum and electrochemistry. The DNA-binding, photocleavage, and topoisomerase inhibition of the complex was studied. Interestingly, the complex binds to DNA via an intercalative mode with preference for GC sequences and cleaves the pBR322 DNA upon irradiation. In addition, the complex shows high inhibition activity against topoisomerase II by interfere the DNA religation.

Alkali-stable phosphorylation of proteins, particularly phosphotyrosine and phosphohistidine, is an important phenomenon in cells. In the case of phosphohistidine and some other phosphoamino acids, the phosphorylation is acid-labile and in these cases studies have been severely limited by the absence of a rapid assay suitable for acid-labile phosphorylation. The assay presented here involves a conventional kinase assay reaction followed by mild alkaline hydrolysis and adsorption of the product to washed Nytran paper at high pH. After further washing, at pH 9, the radioactivity on the papers is determined by liquid scintillation counting. Hence, acid-labile phosphorylation is preserved. The assay is selective for alkali-stable phosphorylation but not fully specific, mainly due to the need to balance the severity of the partial alkaline hydrolysis with the stability of the protein-peptide bonds. The assay has been used for the purification and characterization of a protein histidine kinase from Saccharomyces cerevisiae.

Analysis of peptides purified from high and low molecular weight fractions of rabbit atrial extracts indicates that the sequence of the first 30 residues of rabbit atriopeptigen exhibits 80% homology with the rat peptide, and that the low molecular weight rabbit peptide (28 residues) is identical to rat atriopeptin 28 (AP 28). The effects of infused 1-deaminoarginine8-vasopressin (dAVP) and phenylephrine, volume expansion, and water immersion on AP release into the circulation of the rabbit was studied. Neither dAVP, nor water immersion elevated right atrial pressure (RAP) or plasma AP levels in the anesthetized rabbits. Phenylephrine induced a sustained increase in systemic blood pressure and right atrial pressure which was accompanied by elevated plasma AP immunoreactivity which appeared to be identical to rat AP-28 on HPLC. There is obviously a preferential conservation of the AP sequence, since the C-terminal peptide is exactly the same in rabbit, rat and mouse and differs from human, dog, cow and pig only by the single substitution of an isoleucine for a methionine residue.

A rapid, convenient, and sensitive enzyme immunoassay (EIA) for atriopeptin (AP) has been developed. The tracer-ligand for the assay is the 24-amino acid peptide, AP24, which has been covalently coupled to the tetrameric form of acetylcholinesterase (AChE) (EC 3.1.1.7). Tracer, unknown, and primary antibody are incubated in a 96-well microtiter plate precoated with secondary antibody. After washing, a colorimetric reaction is used to measure acetylcholinesterase activity. A direct linear correlation was obtained when comparing the conventional radioimmunoassay and the EIA by using the same primary antibody to assay: plasma samples (rat or human), HPLC column fractions, or atrial extracts. Besides being technically much less demanding and not requiring the use of the radioisotopes, the EIA is more sensitive than the radioimmunoassay and thereby lends itself to a "flash" same-day assay of samples.

Histone H4 is a good substrate in vitro for the protein histidine kinase activity found both in Physarum polycephalum nuclear extracts and in Saccharomyces cerevisiae cell extracts. However, histone H4 in nucleosome core particles is not a substrate for these kinases. Isolated chromatin was also not a substrate for the protein histidine kinase. The results significantly limit possible interpretations of histidine phosphorylation on histone H4 in vivo and provide a new, sharper focus for future work. In addition, a polynucleotide kinase activity was identified in the Physarum extracts.