Publications by authors named "Juan Lin"

282 Publications

Improving Cβ-stereoselectivity of L-threonine Aldolase for Synthesis of L-threo-4-methylsulfonylphenylserine by Modulating Substrate-binding Pocket for Orientation Control of Substrate Entrance.

Chemistry 2021 Apr 11. Epub 2021 Apr 11.

Fuzhou University, college of biological science and engineering, CHINA.

L-threonine aldolase form Actinocorallia herbida (AhLTA) is an ideal catalyst for producing L-threo-4-methylsulfonylphenylserine [(2S, 3R)-1b], a key chiral precursor for florfenicol and thiamphenicol. The moderate Cβ-stereoselectivity is the main obstacle for the industrial application of AhLTA. To address this issue, combinatorial active-site saturation test (CAST) joined with sequence conservatism analysis were applied to engineer the AhLTA toward improved Cβ-stereoselectivity. The optical mutant Y314R could asymmetrically synthesize L-threo-4-methylsulfonylphenylserine with 81% de (diastereomeric excess), which is 23% higher than wild-type AhLTA. Molecular Dynamic (MD) simulations have revealed that the mechanism for Cβ-stereoselectivity improvement of Y314R is due to the acylamino group of residues Arg314 controlling the orientation of substrate 4-methylsulphonyl benzaldehyde (1a) into the active pocket by directed interaction with the methylsulphonyl group, which leads to asymmetric synthesis of L-threo-4-methylsulfonylphenylserine. The success in the present study demonstrates that direct control of substrates into an active pocket is an attract strategy to address Cβ-stereoselectivity problem of LTA, which contributes to the industrial application of LTA.
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http://dx.doi.org/10.1002/chem.202100752DOI Listing
April 2021

Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort.

Cancers (Basel) 2021 Mar 23;13(6). Epub 2021 Mar 23.

Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, USA.

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races ( = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction ( = 0.81 and = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test ( = 0.016) and multivariate Cox regression (HR 0.48, = 0.09 for White and HR 0.36, = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test ( = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study.
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http://dx.doi.org/10.3390/cancers13061464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004603PMC
March 2021

B7-H3 and PD-L1 Expression Are Prognostic Biomarkers in a Multi-racial Cohort of Patients with Colorectal Cancer.

Clin Colorectal Cancer 2021 Feb 19. Epub 2021 Feb 19.

Montefiore Medical Center, Bronx, NY; Albert Einstein College of Medicine, Bronx, NY. Electronic address:

Background: Immunotherapy has emerged as an effective and durable treatment modality for solid cancers. However, its use in colorectal cancer (CRC) is limited to deficient mismatch repair (dMMR) tumors. As such, assessing immune regulatory proteins from the B7-CD28 family, other than PD-1, PD-L1, and CTLA-4, is critical. This study aimed to evaluate the expression of novel protein regulators in a racially diverse population of patients with CRC.

Methods: A tumor microarray was created for 214 samples from a multiracial patient population with metastatic CRC, and expression of HHLA2, B7-H3, PD-L1, CK7, CK20, and CDX2 was determined. The expression pattern was scored as 0 to 12, based on tumor tissue prevalence and the intensity. Clinical information was obtained by chart review and vital statistics from the National Death Index. Associations between low and high expression groups for each protein by race/ethnic groups were assessed, and Kaplan-Meier curves were plotted to evaluate association with survival.

Results: The median age at diagnosis was 61 years, with a female predominance. The majority of the patients were diagnosed with de novo metastatic disease with left-sided, moderately differentiated tumors. There were no racial disparities in the expression of any protein. Overall, a high frequency of tumors had no expression of B7-H3 (62.5%) or PD-L1 (43.5%). Low expression of both PD-L1 and B7-H3 was a significant prognostic biomarker associated with better survival (median overall survival, 43.3 months vs. 24.6 months; P < .01).

Conclusion: In this multiracial tumor microarray of CRC samples, low PD-L1 and B7-H3 expression was associated with an improved prognosis. There was no significant variation among races with respect to the relevant CRC protein markers.
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http://dx.doi.org/10.1016/j.clcc.2021.02.002DOI Listing
February 2021

Interaction between the cell walls of microalgal host and fungal carbohydrate-activate enzymes is essential for the pathogenic parasitism process.

Environ Microbiol 2021 Mar 15. Epub 2021 Mar 15.

Center for Microalgal Biotechnology and Biofuels, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Fungi can parasitize microalgae, exerting profound impacts on both the aquatic ecosystems and microalgal mass cultures. In this study, the unicellular green alga Haematococcus pluvialis and the blastocladialean fungus Paraphysoderma sedebokerense, were used as a model system to address the mechanisms underlying the fungal parasitism on the algal host. High-throughput metabolic assay indicated that P. sedebokerense can utilize several carbon sources with a preference for mannose, glucose and their oligosaccharides, which was compatible with the profile of the host algal cell walls enriched with glucan and mannan. The results of dual transcriptomics analysis suggested that P. sedebokerense can up-regulate a large number of putative carbohydrate-activate enzymes (CAZymes) encoding genes, including those coding for the endo-1,4-β-glucanase and endo-1,4-β-mannanase during the infection process. The cell walls of H. pluvialis can be decomposed by both P. sedebokerense and commercial CAZymes (e.g. cellulase and endo-1,4-β-mannanase) to produce mannooligomers, while several putative parasitism-related genes of P. sedebokerense can be in turn up-regulated by mannooligomers. In addition, the parasitism can be blocked through interfering the selected CAZymes including glucanase, mannanase, and lysozyme with the specific inhibitors, which provided a framework for screening suitable compounds for pathogen mitigation in algal mass culture. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/1462-2920.15465DOI Listing
March 2021

Efficient biosynthesis of (2S, 3R)-4-methylsulfonylphenylserine by artificial self-assembly of enzyme complex combined with an intensified acetaldehyde elimination system.

Bioorg Chem 2021 Feb 24;110:104766. Epub 2021 Feb 24.

College of Chemical Engineering, Fuzhou University, Fuzhou 350116, China; College of Biological Science and Engineering, Fuzhou University, Fuzhou 350116, China. Electronic address:

(2S, 3R)-4-methylsulfonylphenylserine [(2S, 3R)-MPS], a key chiral precursor for antibiotics florfenicol and thiamphenicol, could be asymmetrically synthesized by l-threonine transaldolase (LTTA) coupled with an acetaldehyde elimination system. The low efficiency of acetaldehyde elimination system blocked further accumulation of (2S, 3R)-MPS. To address this issue, strengthening acetaldehyde elimination system and enzyme self-assembly strategy were combined to accelerate biosynthesis of (2S, 3R)-MPS. The new multi-enzyme cascade with intensified acetaldehyde elimination system BL21 (PsLTTAD2/ScADH/BtGDH) could produce (2S, 3R)-MPS with a titer of 157.6 mM, 1.7-folds than that produced by the original system BL21 (PsLTTAD2/ApADH/CbFDH). Moreover, self-assembly of PsLTTAD2 and ScADH by respective fusion of SpyTag and SpyCatcher were carried out to develop a self-assembled multi-enzyme cascade BL21 (ST-PsLTTAD2/SC-ScADH/BtGDH). As a result, the yield of (2S, 3R)-MPS was up to 248.1 mM with 95% de. As far as we knew, that represented the highest yield of (2S, 3R)-MPS by enzymatic synthesis, and therefore was a promising and green route for industrial production of this valuable compound.
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http://dx.doi.org/10.1016/j.bioorg.2021.104766DOI Listing
February 2021

Lymphovascular invasion, race, and the 21-gene recurrence score in early estrogen receptor-positive breast cancer.

NPJ Breast Cancer 2021 Mar 1;7(1):20. Epub 2021 Mar 1.

Montefiore Einstein Center for Cancer Care, Bronx, NY, USA.

Lymphovascular invasion (LVI) and Black race are associated with poorer prognosis in early breast cancer (EBC). We evaluated the association between LVI and race, and whether LVI adds prognostic benefit to the 21-gene recurrence score (RS) in EBC. Women with ER+ HER2- EBC measuring up to 5 cm, with 0-3 involved axillary nodes, diagnosed between 1 January 2010 and 1 January 2014, who underwent surgery as first treatment and had available RS, were identified in the NCDB database. Bivariate associations between two categorical variables were examined using chi-square test. Multivariate Cox proportional hazards model were used to assess the association of LVI, race, and other covariates with overall survival (OS). 77,425 women, 65,018 node-negative (N0), and 12,407 with 1-3 positive (N+) nodes, were included. LVI was present in 12.7%, and associated with poor grade, RS 26-100, and N+ (all p < 0.0001), but not Black race. In multivariate analysis, LVI was associated with worse OS in N0 [HR 1.37 (95% CI 1.27, 1.57], but not N+ EBC. LVI was associated with worse OS in N0 patients with RS 11-25 [HR 1.31 (95% CI 1.09, 1.57)] and ≥26 [HR 1.58 (95% CI 1.30, 1.93)], but not RS 0-10. No interaction between LVI and chemotherapy benefit was seen. Black race was associated with worse OS in N0 (HR 1.21, p = 0.009) and N+ (HR 1.37, p = 0.015) disease. LVI adds prognostic information in ER+, HER2-, N0 BCA with RS 11-100, but does not predict chemotherapy benefit. Black race is associated with worse OS, but not LVI.
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http://dx.doi.org/10.1038/s41523-021-00231-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921089PMC
March 2021

Etomidate propofol in coronary heart disease patients undergoing major noncardiac surgery: A randomized clinical trial.

World J Clin Cases 2021 Feb;9(6):1293-1303

Department of Geriatrics, The First Affiliated Hospital of Southern University, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518020, Guangdong Province, China.

Background: The ideal depth of general anesthesia should achieve the required levels of hypnosis, analgesia, and muscle relaxation while minimizing physiologic responses to awareness. The choice of anesthetic strategy in patients with coronary heart disease (CHD) undergoing major noncardiac surgery is becoming an increasingly important issue as the population ages. This is because general anesthesia is associated with a risk of perioperative cardiac complications and death, and this risk is much higher in people with CHD.

Aim: To compare hemodynamic function and cardiovascular event rate between etomidate- and propofol-based anesthesia in patients with CHD.

Methods: This prospective study enrolled consecutive patients (American Society of Anesthesiologists grade II/III) with stable CHD (New York Heart Association class I/II) undergoing major noncardiac surgery. The patients were randomly allocated to receive either etomidate/remifentanil-based or propofol/remifentanil-based general anesthesia. Randomization was performed using a computer-generated random number table and sequentially numbered, opaque, sealed envelopes. Concealment was maintained until the patient had arrived in the operating theater, at which point the consulting anesthetist opened the envelope. All patients, data collectors, and data analyzers were blinded to the type of anesthesia used. The primary endpoints were the occurrence of cardiovascular events (bradycardia, tachycardia, hypotension, ST-T segment changes, and ventricular premature beats) during anesthesia and cardiac troponin I level at 24 h. The secondary endpoints were hemodynamic parameters, bispectral index, and use of vasopressors during anesthesia.

Results: The final analysis included 40 patients in each of the propofol and etomidate groups. The incidences of bradycardia, hypotension, ST-T segment changes, and ventricular premature beats during anesthesia were significantly higher in the propofol group than in the etomidate group ( < 0.05 for all). The incidence of tachycardia was similar between the two groups. Cardiac troponin I levels were comparable between the two groups both before the induction of anesthesia and at 24 h after surgery. When compared with the etomidate group, the propofol group had significantly lower heart rates at 3 min after the anesthetic was injected (T) and immediately after tracheal intubation (T), lower systolic blood pressure at T, and lower diastolic blood pressure and mean arterial pressure at T, T, 3 min after tracheal intubation, and 5 min after tracheal intubation ( < 0.05 for all). Vasopressor use was significantly more in the propofol group than in the etomidate group during the induction and maintenance periods ( < 0.001).

Conclusion: In patients with CHD undergoing noncardiac major surgery, etomidate-based anesthesia is associated with fewer cardiovascular events and smaller hemodynamic changes than propofol-based anesthesia.
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http://dx.doi.org/10.12998/wjcc.v9.i6.1293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896684PMC
February 2021

Racial/ethnic disparities in early-onset colorectal cancer: implications for a racial/ethnic-specific screening strategy.

Cancer Med 2021 Mar 28;10(6):2080-2087. Epub 2021 Feb 28.

Department of Medical Oncology, Montefiore Medical Center, Bronx, NY, USA.

Introduction: Early-onset colorectal cancer (EO-CRC) is a public health concern. Starting screening at 45 years has been considered, but there is discrepancy in the recommendations. Racial disparities in EO-CRC incidence and survival are reported; however, racial/ethnic differences in EO-CRC features that could inform a racial/ethnic-tailored CRC screening strategy have not been reported. We compared features and survival among Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanics with EO-CRC.

Methods: CRC patients from SEER 1973-2010 database were identified, and EO-CRC was defined as CRC at <50 years. Clinical/pathological features and survival were compared between NHW, NHB, and Hispanics. Cancer-specific survival (CSS) predictors were assessed in a multivariable Cox proportional hazard model.

Results: Of 166,416 patients with CRC, 16,545 (9.9%) had EO-CRC. The EO-CRC frequencies in NHB and Hispanics were higher than NHW (12.7% vs. 16.5% vs. 8.7%, p < 0.001). EO-CRC in NHB presents more frequently in females, with well/moderately differentiated, stage IV, and is less likely to present in locations targetable by sigmoidoscopy than NHW (54.6% vs. 67.7% OR:1.7, 95% p < 0.001). 5-year CSS was lower in NHB (59.4% vs. 72.8%, HR: 1.7; 95% CI: 1.54-1.82) and Hispanics (66.4% vs. 72.8%, HR: 1.3; 95% CI: 1.16-1.39) than NHW. A regression model among patients with EO-CRC showed that being NHB or Hispanic were independent predictors for cancer-specific mortality, after adjusting for gender, grade, stage, and surgery.

Conclusion: EO-CRC is more likely in NHB and Hispanics. Racial disparities in clinical/pathological features and CSS between NHB and NHW/Hispanics were evidenced. A racial/ethnic specific screening strategy could be considered as an alternative for patients younger than 50 years.
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http://dx.doi.org/10.1002/cam4.3811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957207PMC
March 2021

Can the negative pressures found in obstructive sleep apnea and Eustachian tube dysfunction be related?

Am J Otolaryngol 2021 Feb 18;42(4):102993. Epub 2021 Feb 18.

Department of Otorhinolaryngology-Head and Neck Surgery, Albert Einstein College of Medicine, United States of America.

Objective: The association between obstructive sleep apnea (OSA) and Eustachian tube dysfunction (ETD) is well known. When both exist in a single pediatric patient, one of the expected culprits is adenoid enlargement. We hypothesize, in contrast, that the negative pharyngeal pressure found in OSA may be transmitted to the middle ear as negative middle ear pressure (MEP), which subsequently results in pathology. The objective of this study was to determine whether the degree of OSA and MEP are associated while using MEP as a quantifiable measurement of ETD.

Study Design: Retrospective chart review.

Setting: Tertiary academic center (Jan 2000-Jan 2018).

Subjects And Methods: The relationship between apnea-hypopnea index (AHI) and MEP was examined. A non-anatomic model was utilized to support causality.

Results: Thirty-four pediatric patients and twenty-three adult patients were included in the analysis. REM AHI showed a moderate negative correlation with MEP in children (r = -0.265), and a weak positive correlation with MEP in adults (r = 0.171). Children with an AHI in the severe OSA category had a more negative mean MEP than those in the mild category (p = 0.36). Adults with an AHI in the severe OSA category had a more positive mean MEP than those in the mild category (p = 0.11).

Conclusion: In children, increasing severity of OSA is associated with a negative MEP, suggesting that negative pressure associated with OSA may be transmitted to the middle ear. In adults, increasing severity of OSA is associated with a more positive MEP.
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http://dx.doi.org/10.1016/j.amjoto.2021.102993DOI Listing
February 2021

Racial Diversity Among Histology of Renal Cell Carcinoma at an Urban Medical Center.

Clin Genitourin Cancer 2021 Jan 6. Epub 2021 Jan 6.

Department of Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY. Electronic address:

Background: Non-Hispanic blacks (NHB) with renal cell carcinoma (RCC) are more likely to have papillary RCC (pRCC) than non-Hispanic whites (NHW). Data on histologic subtypes in RCC in Hispanics (H) are also sparse. Previous studies have shown that pRCC is more prevalent in NHB than in NHW, but they analyzed predominantly NHW populations. The Montefiore-Einstein Center for Cancer Care (MECC) serves a predominantly NHB and H population in the Bronx, NY. We investigated histologic subtype specific associations with established RCC risk factors in this population.

Patients And Methods: The MECC tumor registry was used to identify patients ≥ 18 years of age treated with partial or radical nephrectomy between January 2000 and December 2015. An institutional software program and individual chart review were used to obtain demographic data (including self-reported race, age, and sex), pathology data, and RCC risk factors (hypertension, diabetes, renal function, weight). Data were modeled by multinomial logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: A total of 1010 RCC cases were identified. Of these, 232 (23.0%) occurred in NHW, 383 (37.9%) NHB, 181 (17.9%) H, and 214 (21.2%) other. A total of 530 cases (52.5%) were clear cell (ccRCC) histology, 257 (25.4%) pRCC, 100 (9.9%) chromophobe (cRCC), and 123 (12.2%) other. Individuals with pRCC compared to ccRCC were more likely to be NHB than NHW (OR, 4.41; 95% CI, 2.81-6.93) but were less likely to be female (OR, 0.50; 95% CI, 0.35-0.72). Individuals with pRCC were also less likely to be H than NHW (OR, 0.52; 95% CI, 0.27-0.99). Patients with cRCC were also more likely to be NHB than NHW (OR, 2.23; 95% CI, 1.06-4.67).

Conclusion: In the MECC data set, histology of RCC varies by race, confirming earlier reports that non-ccRCC is more common in NHB than NHW. We also report that pRCC is less common in H than NHW.
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http://dx.doi.org/10.1016/j.clgc.2020.12.010DOI Listing
January 2021

Sex-Based Language Differences in Female Pelvic Medicine and Reconstructive Surgery Fellowship Recommendation Letters.

Female Pelvic Med Reconstr Surg 2021 Jan 28. Epub 2021 Jan 28.

From the Albert Einstein College of Medicine, Bronx Department of OB/GYN, Maimonides Medical Center, Brooklyn Department of Epidemiology and Population Health, Albert Einstein College of Medicine Department of OB/GYN, Montefiore Medical Center Department of Urology, Montefiore Medical Center, Bronx, NY.

Introduction: Letters of recommendation (LORs) are a significant component of residency and fellowship applications. Applicant sex may play a role in the language used in letters, which could hinder progress in academic fields, particularly for women. Although differences in language based on applicant sex have been identified in other fields, no prior studies have evaluated LORs for female pelvic medicine and reconstructive surgery (FPMRS) fellowships.

Methods: Letters of recommendations for applicants to an urban, tertiary care academic medical FPMRS fellowship from 2017 to 2019 were collected. Using the Linguistic Inquiry and Word Count program, a licensed text analysis software for academic purposes, we analyzed LORs based on 16 categories. The Wilcoxon rank sum test, Fisher exact test, and a generalized linear mixed model were used for statistical analyses.

Results: A total of 97 fellowship applications were analyzed, yielding 354 LORs; 32 applicants were male, whereas 65 were female. Letters written for male applicants contained significantly more power words (P = 0.022) and significantly less affiliation words (P = 0.025) compared with female counterparts. Differences were maintained after adjusting for age, race/ethnicity, step 1 to step 3 scores, Phi Beta Kappa status, Alpha Omega Alpha status, and writer's sex.

Conclusions: Significant linguistic differences based on applicant sex exist in FPMRS fellowship LORs. Differences are consistent with previous analyses within science and medical fields. These findings did not show a significant association with an applicant's ability to match; however, we did not analyze whether the matched institution was the preferred choice for each applicant.
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http://dx.doi.org/10.1097/SPV.0000000000001023DOI Listing
January 2021

Single-Point Mutation Near Active Center Increases Substrate Affinity of Alginate Lyase AlgL-CD.

Appl Biochem Biotechnol 2021 Jan 23. Epub 2021 Jan 23.

College of Biological Sciences and Engineering, Fuzhou University, Fuzhou, 350108, China.

Alginate lyases have been widely used for the preparation of bioactive alginate oligosaccharides. An alginate lyase AlgL-CD was rationally designed by introducing alkaline amino acid residues near active center to increase activity. One of its mutants E226K presented much higher activity than wild-type AlgL-CD. Substrate affinity of E226K increased 10 folds as the K values indicated. The spectra of intrinsic emission fluorescence and circular dichroism of E226K suggested the whole enzyme turned to be more flexible. The 8-anilino-1-naphthalenesulfonate (ANS)-binding assay showed that the hydrophobic active center of E226K was more available to ligand. Molecular dynamic analysis of the enzyme-substrate complex showed that lid loops of the active center in E226K turned to be more opened up, which might contribute to the increase of substrate-binding affinity. Meanwhile, the catalytic residue of E226K was closer to the hydrogen donor C5 atom of the substrate to increase catalysis rate. The final degradation products of alginate by E226K were determined to be identical with that of AlgL-CD. This study provides guidance for improving enzymatic preparation efficiency of bioactive alginate oligosaccharides.
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http://dx.doi.org/10.1007/s12010-021-03507-xDOI Listing
January 2021

Laboratory investigation on calcium nitrate induced coupling reactions between nitrogen, phosphorus, sulfur, and metals in contaminated sediments.

Environ Sci Pollut Res Int 2021 Jan 21. Epub 2021 Jan 21.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China.

In recent years, calcium nitrate addition has become a promising and usually used method for in situ sediment remediation. In this study, excess calcium nitrate was applied to column sediments to explore the coupling reactions of elements such as N, Fe, S, and P. Diffusive gradients in thin film (DGT) devices were used to collect labile substances at the sediment-water interface. Rhizon samplers were used to collect soluble substances in interstitial water. Results showed that nitrate addition turned the surface sediment into a more oxidized state, and mobile Fe, S, P, and As were removed in surface ~ 10-cm sediment. Due to different nitrate distributions in corresponding sediment depths, the consumption rates of NH-N and soluble reactive P were faster in the surface sediment than that in deeper layers. Different from previous researches, the transient increase of soluble Fe was observed in this study, which was probably attributed to the solvation of FeS in the autotrophic denitrification process. According to our results, we suggest that a dosage of far less than 141 g N/m and slightly more than 45.3 g N/m can be used for the remediation of black and odorous sediment and control of internal P by calcium nitrate.
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http://dx.doi.org/10.1007/s11356-021-12441-8DOI Listing
January 2021

Disulfide Cross-Linked Poly(Methacrylic Acid) Iron Oxide Nanoparticles for Efficiently Selective Adsorption of Pb(II) from Aqueous Solutions.

ACS Omega 2021 Jan 28;6(1):976-987. Epub 2020 Dec 28.

Key Laboratory of Basic Chemistry of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, First Ring Road, 4th Section No. 16, 610041 Chengdu, China.

The efficient selectivity of heavy metal ions from wastewater is still challenging but gains great public attention in water treatment on a world scale. In this study, the novel disulfide cross-linked poly(methacrylic acid) iron oxide (FeO@S-S/PMAA) nanoparticles with selective adsorption, improved adsorption capability, and economic reusability were designed and prepared for selective adsorption of Pb(II) ions in aqueous solution. In this study, nuclear magnetic resonance, dynamic light scattering, scanning electron microscopy, X-ray diffraction, vibrating sample magnetometry, and thermogravimetric analysis were utilized to study the chemophysical properties of FeO@S-S/PMAA. The effect of different factors on adsorption properties of the FeO@S-S/PMAA nanoparticles for Co(II) and Pb(II) ions in aqueous solution was explored by batch adsorption experiments. For adsorption mechanism investigation, the adsorption of FeO@S-S/PMAA for Co(II) and Pb(II) ions can be better fitted by a pseudo-second-order model, and the adsorption process of FeO@S-S/PMAA for Co(II) and Pb(II) matches well with the Freundlich isotherm equation. Notably, in the adsorption experiments, the FeO@S-S/PMAA nanoparticles were demonstrated to have a maximum adsorption capacity of 48.7 mg·g on Pb(II) ions with a selective adsorption order of Pb > Co > Cd > Ni > Cu > Zn > K > Na > Mg > Ca in the selective experiments. In the regeneration experiments, the FeO@S-S/PMAA nanoparticles could be easily recovered by desorbing heavy metal ions from the adsorbents with eluents and showed good adsorption capacity for Co(II) and Pb(II) after eight recycles. In brief, compared to other traditional nanoadsorbents, the as-prepared FeO@S-S/PMAA with improved adsorption capability and high regeneration efficiency demonstrated remarkable affinity for adsorption of Pb(II) ions, which will provide a novel technical platform for selective removal of heavy metal ions from actual polluted water.
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http://dx.doi.org/10.1021/acsomega.0c05623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808134PMC
January 2021

Effects of continuous positive airway pressure on plasma fibrinogen levels in obstructive sleep apnea patients: a systemic review and meta-analysis.

Biosci Rep 2021 Jan;41(1)

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.

Objective: Fibrinogen has been implicated to play a role in the pathophysiology of obstructive sleep apnea (OSA). Many studies have evaluated the effect of continuous positive airway pressure (CPAP) on plasma fibrinogen levels in OSA patients. However, results from different reports were not consistent. To assess the effect of CPAP treatment on plasma fibrinogen levels of patients with OSA, a meta-analysis was performed.

Methods: A systematic search of Pubmed, Embase, Cochrane, Wanfang Database and Chinese National Knowledge Infrastructure was performed. Data were extracted, and then weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results: Twenty-two studies involving 859 patients were included in this meta-analysis. Combined data showed that plasma fibrinogen concentrations decreased after CPAP therapy (WMD = -0.38 g/l, 95% CI [-0.54 to -0.22 g/l], P<0.001). In the subgroup analyses by therapy duration, plasma fibrinogen concentrations declined significantly in the long-term (≥1 month) CPAP therapy subgroup (WMD = -0.33 g/l, 95% CI [-0.49 to -0.16 g/l], P<0.001) but not in the short-term (<1 month) CPAP therapy subgroup (WMD = -0.84 g/l, 95% CI [-1.70 to 0.03 g/l], P=0.058). Moreover, in patients with long-term CPAP therapy duration, plasma fibrinogen levels decreased with good CPAP compliance (≥4 h/night) (WMD = -0.37 g/l, 95% CI [-0.55 to -0.19 g/l], P<0.001) but not with poor CPAP compliance (<4 h/night) (WMD = 0.12 g/l, 95% CI [-0.09 to 0.33 g/l], P=0.247).

Conclusion: Long-term CPAP treatment with good compliance can reduce the plasma fibrinogen levels in patients with OSA.
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http://dx.doi.org/10.1042/BSR20203856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846965PMC
January 2021

Diagnostic significance of the CT rim sign in cases of gangrenous cholecystitis.

Clin Imaging 2021 May 3;73:53-56. Epub 2020 Dec 3.

Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, United States of America.

Purpose: To evaluate the association between the CT rim sign and gangrenous cholecystitis (GC) and increased surgical difficulty.

Method: Patients who had a contrast enhanced CT of the abdomen and pelvis, followed by non-elective cholecystectomy were analyzed. The scans were reviewed for the CT rim sign by radiologists blinded to the pathologic and clinical outcomes. Demographic and clinical characteristics were compared between patients with and without GC using t-tests or Wilcoxon ranked sum test for continuous variables, and Fishers' exact test for categorical variables, when appropriate. A logistic regression model was fitted with multiple risk factors. Odds ratios as well as 95% confidence intervals were then calculated for the risk factors. A secondary analysis predicting increased surgical difficulty, defined as an operative time of greater than 2 h or increased conversion rate to open surgery, was also examined.

Results: A total of 100 patients were included; 20 of which had GC. On imaging, patients with GC were more likely to have a CT rim sign (65% vs 32.5%, OR = 3.80, 95% CI: 1.24-12.7, p = 0.011). The presence of the CT rim sign did not reach a statistically significant association with an operative time >2 h or conversion to open case (56.52% vs 33.77%, OR = 2.55, p = 0.056).

Conclusion: The CT rim sign can be utilized to raise the possibility of GC, however the presence of the CT rim sign does not demonstrate an association with increased surgical difficulty.
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http://dx.doi.org/10.1016/j.clinimag.2020.11.052DOI Listing
May 2021

Peroral traction-assisted natural orifice trans-anal flexible endoscopic rectosigmoidectomy followed by intracorporeal colorectal anastomosis in a live porcine model.

World J Gastrointest Endosc 2020 Nov;12(11):451-458

School of Clinical Medicine, Fujian Medical University, Fuzhou 350122, Fujian Province, China.

Background: Compared to traditional open surgery, laparoscopic surgery has become a standard approach for colorectal cancer due to its great superiorities including less postoperative pain, a shorter hospital stay, and better quality of life. In 2007, Whiteford reported the first natural orifice trans-anal endoscopic surgery (NOTES) sigmoidectomy using transanal endoscopic microsurgery. To date, all cases of NOTES colorectal resection have included a hybrid laparoscopic approach with the use of established rigid platforms.

Aim: To introduce a novel technique of peroral external traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis by using only currently available and flexible endoscopic instrumentation in a live porcine model.

Methods: Three female pigs weighing 25-30 kg underwent NOTES rectosigmoid resection. After preoperative work-up and bowel preparation, general anesthesia combined with endotracheal intubation was achieved. One dual-channel therapeutic endoscope was used. Carbon dioxide insufflation was performed during the operation. The procedure of trans-anal NOTES rectosigmoidectomy included the following eight steps: (1) The rectosigmoid colon was tattooed with India ink by submucosal injection; (2) Creation of gastrostomy by directed submucosal tunneling; (3) Peroral external traction using endoloop ligation; (4) Creation of rectostomy on the anterior rectal wall by directed 3 cm submucosal tunneling; (5) Peroral external traction-assisted dissection of the left side of the colon; (6) Trans-anal rectosigmoid specimen transection, where an anvil was inserted into the proximal segment after purse-string suturing; (7) Intracorporeal colorectal end-to-end anastomosis using a circular stapler by a single stapling technique; and (8) Closure of gastrostomy using endoscopic clips. All animals were euthanized immediately after the procedure, abdominal exploration was performed, and the air-under-water leak test was carried out.

Results: The procedure was completed in all three animals, with the operation time ranging from 193 min to 259 min. Neither major intraoperative complications nor hemodynamic instability occurred during the operation. The length of the resected specimen ranged from 7 cm to 13 cm. With the assistance of a trans-umbilical rigid grasper, intracorporeal colorectal, tension-free, end-to-end anastomosis was achieved in the three animals.

Conclusion: Peroral traction-assisted transanal NOTES rectosigmoidectomy followed by intracorporeal colorectal end-to-end anastomosis is technically feasible and reproducible in an animal model and is worthy of further improvements.
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http://dx.doi.org/10.4253/wjge.v12.i11.451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677887PMC
November 2020

Utility of a custom designed next generation DNA sequencing gene panel to molecularly classify endometrial cancers according to The Cancer Genome Atlas subgroups.

BMC Med Genomics 2020 11 30;13(1):179. Epub 2020 Nov 30.

Department of Genetics, Albert Einstein College of Medicine, Price Center/Block Research Pavilion, Room 401, 1301 Morris Park Avenue, Bronx, NY, 10461, USA.

Background: The Cancer Genome Atlas identified four molecular subgroups of endometrial cancer with survival differences based on whole genome, transcriptomic, and proteomic characterization. Clinically accessible algorithms that reproduce this data are needed. Our aim was to determine if targeted sequencing alone allowed for molecular classification of endometrial cancer.

Methods: Using a custom-designed 156 gene panel, we analyzed 47 endometrial cancers and matching non-tumor tissue. Variants were annotated for pathogenicity and medical records were reviewed for the clinicopathologic variables. Using molecular characteristics, tumors were classified into four subgroups. Group 1 included patients with > 570 unfiltered somatic variants, > 9 cytosine to adenine nucleotide substitutions per sample, and < 1 cytosine to guanine nucleotide substitution per sample. Group 2 included patients with any somatic mutation in MSH2, MSH6, MLH1, PMS2. Group 3 included patients with TP53 mutations without mutation in mismatch repair genes. Remaining patients were classified as group 4. Analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, North Carolina, USA).

Results: Endometrioid endometrial cancers had more candidate variants of potential pathogenic interest (median 6 IQR 4.13 vs. 2 IQR 2.3; p < 0.01) than uterine serous cancers. PTEN (82% vs. 15%, p < 0.01) and PIK3CA (74% vs. 23%, p < 0.01) mutations were more frequent in endometrioid than serous carcinomas. TP53 (18% vs. 77%, p < 0.01) mutations were more frequent in serous carcinomas. Visual inspection of the number of unfiltered somatic variants per sample identified six grade 3 endometrioid samples with high tumor mutational burden, all of which demonstrated POLE mutations, most commonly P286R and V411L. Of the grade 3 endometrioid carcinomas, those with POLE mutations were less likely to have risk factors necessitating adjuvant treatment than those with low tumor mutational burden. Targeted sequencing was unable to assign samples to microsatellite unstable, copy number low, and copy number high subgroups.

Conclusions: Targeted sequencing can predict the presence of POLE mutations based on the tumor mutational burden. However, targeted sequencing alone is inadequate to classify endometrial cancers into molecular subgroups identified by The Cancer Genome Atlas.
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http://dx.doi.org/10.1186/s12920-020-00824-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706212PMC
November 2020

Phylogenetic and ion-response analyses reveal a relationship between gene expansion and functional divergence in the Ca/cation antiporter family in Angiosperms.

Plant Mol Biol 2021 Feb 29;105(3):303-320. Epub 2020 Oct 29.

State Key Laboratory of Genetic Engineering, Institute of Plant Biology, Shanghai Engineering Research Center of Industrial Microorganisms, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China.

Key Message: Plant CaCA superfamily genes with higher tendency to retain after WGD are more gene expression and function differentiated in ion-response. Plants and animals face different environmental stresses but share conserved Ca signaling pathways, such as Ca/Cation transport. The Ca/cation antiporters superfamily (CaCAs) is an ancient and widespread family of ion-coupled cation transporters found in all kingdoms of life. We analyzed the molecular evolution progress of the family through comparative genomics and phylogenetics of CaCAs genes from plants and animals, grouping these genes into several families and clades, and identified multiple gene duplication retention events, particularly in the CAX (H/cation exchanger), CCX (cation/Ca exchanger), and NCL (Na/Ca exchanger-like) families. The tendency of duplication retention differs between families and gene clades. The gene duplication events were probably the result of whole-genome duplication (WGD) in plants and might have led to functional divergence. Tissue and ion-response expression analyses revealed that CaCAs genes with more highly differentiated expression patterns are more likely to be retained as duplicates than those with more conserved expression profiles. Phenotype of Arabidopsis thaliana mutants showed that loss of genes with a greater tendency to be retained after duplication resulted in more severe growth deficiency. CaCAs genes in salt-tolerant species tended to inherit the expression characteristics of their most recent common ancestral genes, with conservative ion-response expression. This study indicates a possible evolutionary scheme for cation transport and illustrates distinct fates and a mechanism for the evolution of gene duplicates. The increased copy numbers of genes and divergences in expression might have contributed to the divergent functions of CaCAs protein, allowing plants to cope with environmental stresses and adapt to a larger number of ecological niches.
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http://dx.doi.org/10.1007/s11103-020-01088-7DOI Listing
February 2021

Very-low-dose decitabine treatment for patients with intermediate- or high-risk myelodysplastic syndrome: a retrospective analysis of thirteen cases.

Ann Hematol 2020 Nov 17;99(11):2539-2546. Epub 2020 Sep 17.

Department of Hematology, Chengdu First People's Hospital, Chengdu, 610041, Sichuan Province, China.

Decitabine is a hypomethylating drug that is used to treat myelodysplastic syndrome (MDS) at a recommended dose and schedule (20 mg/m per day, for 5 consecutive days). However, due to its relatively high incidence of side effects and its effects on neoplastic cells, many studies have begun to explore the clinical application of a low dose of decitabine for treating MDS. In this retrospective study, we examined the effects of a very-low-dose decitabine schedule for treating MDS. A total of 13 patients diagnosed with de novo MDS received a schedule of intravenous decitabine administration at 6 mg/m per day for 7 days, repeated every 4 weeks. The complete response rate was 30.8%, and the overall response rate was 69.2%. In patients with complete remission, the median time to granulocyte recovery greater than 0.5 × 10/L during complete remission (CR) was 15 days. In patients with remission, the median time to granulocyte recovery greater than 0.5 × 10/L was 10.5 days. The 1-year survival rate was 72.7% and the median survival was 28.0 months. In summary, we demonstrated that a very-low-dose decitabine schedule has an appreciable response and survival rate, as well as appreciable tolerance and medical compliance for treating MDS.
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http://dx.doi.org/10.1007/s00277-020-04268-zDOI Listing
November 2020

[Investigation of nurses' attitude towards open visitation policy in intensive care unit and analysis of influence factors].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Aug;32(8):998-1002

Department of Intensive Care Unit, Zhejiang Hospital, Hangzhou 310013, Zhejiang, China. Corresponding author: Ren Qi, Email:

Objective: To investigate the nurses' attitude towards open visitation policy in intensive care unit (ICU) and its potential influence factors, and further to provide evidence for carrying out this policy in ICU.

Methods: A self-designed, anonymous online questionnaire of "attitude of ICU nurses to open visiting system in ICU" was performed in 31 provinces, autonomous regions and municipalities in China from October to December 2019, using convenient sampling method approach. Only nurses working in ICU (including specialized ICU, but excluding the critical ward in general ward) and willing to participate in the survey were included. The survey included 35 items, including the general information of each participant, the attitude towards the implementation of the open visitation system in ICU and its potential influencing factors. Ordinal Logistic regression analysis was used to identify the significant influencing factors.

Results: A total of 1 558 questionnaires were sent out and 1 546 effective questionnaires were retrieved, with a response rate of 99.2%. Overall, 32.2% of them agreed with the policy, 41.3% of them disagree with the policy and 26.5% of them were uncertain. The Ordinal Logistic regression analysis showed that the independent influencing factors of ICU nurses' attitude towards open visitation policy including the possibility of increasing healthcare-associated infection [disagree: β = 1.327, 95% confidence interval (95%CI) was 0.242 to 2.413, P = 0.017; uncertain: β = 0.697, 95%CI was 0.244 to 1.151, P = 0.003], the improvement of nurses' job satisfaction (disagree: β = -1.406, 95%CI was -1.750 to -1.062, P = 0.000; uncertain: β = -0.748, 95%CI was -1.030 to -0.466, P = 0.000), the information support for medical staffs from family members (disagree: β = -0.644, 95%CI was -1.048 to -0.240, P = 0.002; uncertain: β = -0.422, 95%CI was -0.721 to -0.124, P = 0.006), the feasibility that the family members can assist the nurses in the basic nursing for patients (uncertain: β = -0.465, 95%CI was -0.729 to -0.202, P = 0.001), reducing the time that a nurse spent on caring for the patients (uncertain: β = 0.349, 95%CI was 0.052 to 0.646, P = 0.021), improving early rehabilitation (disagree: β = -0.593, 95%CI was -1.166 to -0.019, P = 0.043), and getting psychological support for patients from family members (disagree: β = 1.293, 95%CI was 0.426 to 2.159, P = 0.003), family members' satisfaction (disagree: β = -0.981, 95%CI was -1.431 to -0.531, P = 0.000).

Conclusions: ICU nurses in China have realized that open visitation policy has positive effect on patients' early rehabilitation, willing to live and satisfaction; meanwhile, this policy may need more improvement in many ways such as healthcare-associated infection control, disinfection and isolation, allocation of human resources and time spent treating and caring for patients.
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http://dx.doi.org/10.3760/cma.j.cn121430-20200408-00460DOI Listing
August 2020

New application of lanthanum-modified bentonite (Phoslock) for immobilization of arsenic in sediments.

Environ Sci Pollut Res Int 2021 Jan 31;28(2):2052-2062. Epub 2020 Aug 31.

College of Life and Environmental Science, Hunan University of Arts and Science, Changde, 415000, China.

Lanthanum-modified bentonite (LMB, Phoslock) is a well-known capping agent for phosphorus immobilization in sediments. Herein, LMB was used to immobilize As in sediments. Batch capacity experiments for arsenate and arsenite adsorption were carried out to obtain adsorption isotherms and kinetics using the Langmuir and Freundlich model calculations. High-resolution (HR) diffusive gradients in thin films (DGT) were applied to monitor the changes of weakly bound As fraction near sediment-water interface (SWI). The interaction of As(III) and As(V) with LMB was influenced by pH and initial mineral composition. As(V) was more obviously adsorbed than As(III) at pH 4 to 9, with mean adsorption of 3.89 mg g and 0.04 mg g, respectively, while at pH > 9 As(III) was preferentially adsorbed. After LMB amendment for 2 months, the maximum As removal efficiency in the pore and overlying water reached 84.5% and 99.3%, respectively. The capping agent remained stable in the top sediments, while the maximum DGT labile As content decreased to 0.89 and 0.51 μg L in dosage-and time-treatments. The As concentration inflection point moved down to a deeper layer. As species changed from labile exchangeable-As to Fe-oxide-bound and residual As. The proportion of mobile As finally decreased to 10.5% of the total As in the upper 20-mm layer sediment. The increase of K (the distribution coefficient at SWI) and k (adsorption rate constant) and the decrease of T (response time of (de)sorption) in the DGT-induced fluxes model (DIFS) indicated the time-dependent impediment of As release from the sediment due to LMB immobilization.
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http://dx.doi.org/10.1007/s11356-020-10565-xDOI Listing
January 2021

Contrast-enhanced transrectal ultrasound can reduce collection of unnecessary biopsies when diagnosing prostate cancer and is predictive of biochemical recurrence following a radical prostatectomy in patients with localized prostate cancer.

BMC Urol 2020 Jul 16;20(1):100. Epub 2020 Jul 16.

Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, No.58 ZhongShan 2nd Road, Guangzhou, 510080, Guangdong, P. R. China.

Background: To investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer.

Methods: This was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy.

Results: A total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8-56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00-24.69; p = 0.002).

Conclusions: CETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.
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http://dx.doi.org/10.1186/s12894-020-00659-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364623PMC
July 2020

Classical monocyte transcriptomes reveal significant anti-inflammatory statin effect in women with chronic HIV.

Cardiovasc Res 2021 Mar;117(4):1166-1177

Laboratory of Inflammation Biology, La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.

Aims: During virally suppressed chronic HIV infection, persistent inflammation contributes to the development of cardiovascular disease (CVD), a major comorbidity in people living with HIV (LWH). Classical blood monocytes (CMs) remain activated during antiretroviral therapy and are a major source of pro-inflammatory and pro-thrombotic factors that contribute to atherosclerotic plaque development and instability.

Methods And Results: Here, we identify transcriptomic changes in circulating CMs in peripheral blood mononuclear cell samples from participants of the Women's Interagency HIV Study, selected by HIV and subclinical CVD (sCVD) status. We flow-sorted CM from participants of the Women's Interagency HIV Study and deep-sequenced their mRNA (n = 92). CMs of HIV+ participants showed elevated interleukin (IL)-6, IL-1β, and IL-12β, overlapping with many transcripts identified in sCVD+ participants. In sCVD+ participants LWH, those reporting statin use showed reduced pro-inflammatory gene expression to a level comparable with healthy (HIV-sCVD-) participants. Statin non-users maintained an elevated inflammatory profile and increased cytokine production.

Conclusion: Statin therapy has been associated with a lower risk of cardiac events, such as myocardial infarction in the general population, but not in those LWH. Our data suggest that women LWH may benefit from statin therapy even in the absence of overt CVD.
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http://dx.doi.org/10.1093/cvr/cvaa188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983000PMC
March 2021

Prepregnancy body mass indexes are associated with perinatal outcomes in females with preeclampsia.

Exp Ther Med 2020 Jul 22;20(1):500-504. Epub 2020 Apr 22.

Department of Obstetrics and Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350000, P.R. China.

The present study aimed to determine the clinical characteristics and perinatal outcomes of females with severe preeclampsia according to their pre-pregnancy body mass index (BMI). Data from 233 patients with severe preeclampsia were reviewed from the Inpatient Obstetrics Department. The data were divided into 3 groups according to the patients' pre-pregnancy BMI: Normal (BMI of 18-25 kg/m; n=134); underweight (BMI <18 kg/m; n=15); and overweight and obese (BMI >25 kg/m; n=84). The incidence of dyslipidemia, amniotic fluid abnormalities and neonatal hospitalizations in the group of females who were overweight or obese before pregnancy were higher than those in the other groups (all P<0.05). In conclusion, the presence of dyslipidemia, excessive weight and obesity prior to pregnancy in patients with severe preeclampsia was associated with maternal and perinatal outcomes.
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http://dx.doi.org/10.3892/etm.2020.8677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271714PMC
July 2020

Having a Primary Care Provider is the Strongest Predictor of Successful Follow-up of Participants in a Clinical Trial.

J Am Board Fam Med 2020 May-Jun;33(3):431-439

From Department of Radiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (SHF, LBH, JML); Department of Family and Social Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (COC); Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (COC, LBH, JML); Department of Epidemiology & Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY (JL); Current Address: Department of Family Medicine, Overlook Medical Center, Summit, NJ (SHF).

Purpose: Ethnic minorities, women, and those of low socioeconomic status are widely underrepresented in clinical trials. Few studies have explored factors associated with successful follow-up in these historically difficult-to-reach patients. This study's objective was to identify patient characteristics and methods of contact that predict successful contact for follow-up in an urban, predominantly ethnic minority, majority-women, poor population to help devise strategies to improve retention.

Methods: We retrospectively reviewed records from a prospective randomized control trial of 400 hospitalized chest pain patients to determine which characteristics were associated with successful telephone follow-up at 1 year after enrollment. We assessed demographic variables, medical history, and social factors by using bivariate analyses. A multivariate analysis was performed using variables from the bivariate analysis with ≤ .2.

Results: The overall successful 1-year follow-up rate was 95% (381/400). Study participants who completed follow-up were significantly more likely to have a primary care physician (PCP) (88% [337/381] versus 68% [13/19]), speak English natively (52% [199/381] versus 26% [5/19]), have a higher Charlson comorbidity index score, and identify as women (64.0% [244/381] versus 42.1% [8/19]). Having a PCP and native English language remained significant at multivariate analysis. Socioeconomic status score, quantity of contact information recorded at recruitment, and insurance status were not significantly associated with successful follow-up.

Conclusions: Patients engaged with the health care system by having a PCP are significantly more likely to achieve follow-up. Successful follow-up is also associated with native English speaking. The potential of improving follow-up by facilitating connections with health care providers requires further study.
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http://dx.doi.org/10.3122/jabfm.2020.03.190018DOI Listing
January 2019

Dexmedetomidine alleviated sepsis‑induced myocardial ferroptosis and septic heart injury.

Mol Med Rep 2020 Jul 4;22(1):175-184. Epub 2020 May 4.

Department of Anesthesiology, Shenzhen People's Hospital and Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518000, P.R. China.

Cardiac dysfunction resulting from sepsis may cause significant morbidity and mortality, and ferroptosis plays a role in this pathology. Dexmedetomidine (Dex), a α2‑adrenergic receptor (α2‑AR) agonist exerts cardioprotective effects against septic heart dysfunction, but the exact mechanism is unknown. In the present study, sepsis was induced by cecal ligation and puncture (CLP) in male C57BL/6 mice. Dex and yohimbine hydrochloride (YOH), an α2‑AR inhibitor, were administered before inducing CLP. Then, 24 h after CLP, serum and heart tissue were collected to detect changes of troponin‑I (TN‑I), interleukin 6 (IL‑6), superoxide dismutase (SOD), malonaldehyde (MDA) and glutathione (GSH) levels, and iron release. Ferroptosis‑targeting proteins, apoptosis and inflammatory factors were assessed by western blotting or ELISA. It was found that, 24 h after CLP, TN‑I, a biomarker of myocardial injury, was significantly increased compared with the control group. Furthermore, the levels of MDA, 8‑hydroxy‑2'‑deoxyguanosine and the inflammatory factors IL‑6 and monocyte chemoattractant protein‑1 were also significantly increased. It was demonstrated that treatment with Dex reverted or attenuated these changes (CLP + Dex vs. CLP; P<0.05), but these protective effects of Dex were reversed by YOH. Moreover, CLP significantly decreased the protein expression levels of glutathione peroxidase 4 (GPX4), SOD and GSH. However, CLP increased expression levels of heme oxygenase‑1 (HO‑1), transferrin receptor, cleaved caspase 3, inducible nitric oxide synthase and gasdermin D, and iron concentrations. It was found that Dex reversed these changes, but YOH abrogated the protective effects of Dex (CLP + Dex + YOH vs. CLP + Dex; P<0.05). Therefore, the present results suggested that the attenuation of sepsis‑induced HO‑1 overexpression and iron concentration, and the reduction of ferroptosis via enhancing GPX4, may be the major mechanisms via which Dex alleviates sepsis‑induced myocardial cellular injury.
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http://dx.doi.org/10.3892/mmr.2020.11114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248514PMC
July 2020

Multi-enzyme cascade for improving β-hydroxy-α-amino acids production by engineering L-threonine transaldolase and combining acetaldehyde elimination system.

Bioresour Technol 2020 Aug 24;310:123439. Epub 2020 Apr 24.

College of Chemical Engineering, Fuzhou University, Fuzhou 350116, China; College of Biological Science and Engineering, Fuzhou University, Fuzhou 350116, China. Electronic address:

L-threonine transaldolase(PsLTTA) could asymmetric synthesize β-hydroxy-α-amino acids (HAAs) with excellentstereoselectivity, while the poor yield limited its further application. Here we provided a combinatorial strategy to improve HAAs production, by directed evolution of PsLTTA towards enhanced activity and introducing an acetaldehyde elimination system to avoid acetaldehyde over-accumulation. A novel high throughput screening (HTS) method for evaluating PsLTTA activity was developed andapplied for directed evolution of PsLTTA. Subsequently, we co-expressedalcohol dehydrogenase andformate dehydrogenase to construct an acetaldehyde elimination system toremove acetaldehyde inhibition.Moreover, the above positive strategies were integrated. As a result,the (2S,3R)-p-methylsulfonyl phenylserine yield reached 154.0 mM andwith 94.6% devalue, the highest productivity and stereoselectivity of (2S,3R)-HAAs reported by enzymatic synthesis so far. Taken together, our studies provided an efficient and green route for chiral synthesis of (2S,3R)-HAAs, which might contribute to the industrialization production of these useful building blocks.
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http://dx.doi.org/10.1016/j.biortech.2020.123439DOI Listing
August 2020

Publisher Correction: Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation.

Nature 2020 04;580(7804):E10

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41586-020-2207-yDOI Listing
April 2020

Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation.

Nature 2020 04 25;580(7803):391-395. Epub 2020 Mar 25.

Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.

The biological function of Z-DNA and Z-RNA, nucleic acid structures with a left-handed double helix, is poorly understood. Z-DNA-binding protein 1 (ZBP1; also known as DAI or DLM-1) is a nucleic acid sensor that contains two Zα domains that bind Z-DNA and Z-RNA. ZBP1 mediates host defence against some viruses by sensing viral nucleic acids. RIPK1 deficiency, or mutation of its RIP homotypic interaction motif (RHIM), triggers ZBP1-dependent necroptosis and inflammation in mice. However, the mechanisms that induce ZBP1 activation in the absence of viral infection remain unknown. Here we show that Zα-dependent sensing of endogenous ligands induces ZBP1-mediated perinatal lethality in mice expressing RIPK1 with mutated RHIM (Ripk1), skin inflammation in mice with epidermis-specific RIPK1 deficiency (RIPK1) and colitis in mice with intestinal epithelial-specific FADD deficiency (FADD). Consistently, functional Zα domains were required for ZBP1-induced necroptosis in fibroblasts that were treated with caspase inhibitors or express RIPK1 with mutated RHIM. Inhibition of nuclear export triggered the Zα-dependent activation of RIPK3 in the nucleus resulting in cell death, which suggests that ZBP1 may recognize nuclear Z-form nucleic acids. We found that ZBP1 constitutively bound cellular double-stranded RNA in a Zα-dependent manner. Complementary reads derived from endogenous retroelements were detected in epidermal RNA, which suggests that double-stranded RNA derived from these retroelements may act as a Zα-domain ligand that triggers the activation of ZBP1. Collectively, our results provide evidence that the sensing of endogenous Z-form nucleic acids by ZBP1 triggers RIPK3-dependent necroptosis and inflammation, which could underlie the development of chronic inflammatory conditions-particularly in individuals with mutations in RIPK1 and CASP8.
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http://dx.doi.org/10.1038/s41586-020-2129-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279955PMC
April 2020