Publications by authors named "Yalan Liu"

164 Publications

Do PFAS changes in landfill leachate treatment systems correlate with changes in physical chemical parameters?

Waste Manag 2022 Aug 1;151:49-59. Epub 2022 Aug 1.

Department of Civil, Architectural, and Environmental Engineering, College of Engineering, University of Miami, Coral Gables, FL 33146, United States. Electronic address:

Per- and polyfluoroalkyl substances (PFAS) have been found at relatively elevated concentrations in landfill leachates. Some landfill facilities treat physical-chemical parameters of their leachates using on-site leachate treatment systems before discharge. The objective of this study was to evaluate whether changes in physical-chemical parameters of leachate at on-site treatment systems (including bulk measurements, oxygen demanding components, and metals) were associated with concentration changes in PFAS. Leachates were evaluated at 15 on-site treatment facilities which included pond systems, aeration tanks, powdered activated carbon (PAC), sand filtration, reverse osmosis (RO) and combination treatment processes. Results show that most physical-chemical parameters and PFAS were significantly reduced in RO systems (over 90 %). For pond systems, statistically significant correlations (r > 0.6, p < 0.05) were observed between ∑PFAS changes and the changes in pH, alkalinity, ammonia, and some metals. Significant correlations were also found between ∑PFAAs precursors changes and specific conductivity (SPC), pH, alkalinity, ammonia, and metals changes. For aeration tank systems, significant correlations (r > 0.6, p < 0.05) were observed between ∑PFAS changes and changes in total dissolved solids and zinc, and between the changes of ∑PFAAs precursors and field pH. These correlations are believed to be associated with rainfall dilution and precipitation of calcium carbonate and other metals as leachate is introduced to the atmosphere.
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http://dx.doi.org/10.1016/j.wasman.2022.07.030DOI Listing
August 2022

The Coordination Chemistry of f-Block Elements in Molten Salts.

Chemistry 2022 Jul 15. Epub 2022 Jul 15.

Institute of High Energy Physics, Chinese Academy of Sciences, Laboratory of Nuclear Energy Chemistry, No.19B Yuquan Road, Shijingshan District, 100049, Beijing, CHINA.

The coordination chemistry of f-block elements (lanthanide and actinide) in molten salts has become a resounding topic in view of its great importance to the research and development (R&D) of molten salt reactors and pyroprocessing. In this concept paper, a general overview of the coordination chemistry of f-block elements in molten salts is provided including past achievements and recent advances. Particular emphases are placed on the oxidation state, speciation, and solution structure of f-block metal ions in molten salts, as well as their relationships with the salt composition. Furthermore, this Concept briefly discusses the spectroscopic and theoretical methods that complement each other in revealing the coordination properties.
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http://dx.doi.org/10.1002/chem.202201145DOI Listing
July 2022

Dual block HER2 assessment increased HER2 immunohistochemistry positive rate in resected specimens of gastric cancer: a prospective multicenter clinical trial from China.

Diagn Pathol 2022 Jun 28;17(1):54. Epub 2022 Jun 28.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Former single center studies indicated that HER2 assessment with two primary tumor blocks (dual block HER2 assessment) could be an efficient and practical approach to overcome the adverse impact of heterogeneity and acquire a HER2 positive rate in gastric cancer (GC). This multicenter prospective clinical trial (NCT02843412) was launched to verify its value and generality.

Methods: A total of 3806 participants with primary GCs have been enrolled from 8 hospitals in China. Two primary tumor blocks were selected and recorded as block 1 and block 2 after histological evaluation. An HER2 (4B5) rabbit monoclonal antibody was used for the immunohistochemistry (IHC) analysis.

Results: In total patients, HER2 IHC positive (3+) rate with dual block assessment (9.4%) was higher than that with single block assessment (block 1: 7.8%, block 2: 7.8%) (P < 0.001). Compared with single-block assessment, dual-block assessment increased the positive rate by approximate 20%. Similarly, HER2 equivocal (2+) rate was increased in dual block assessment (25.8%), which was higher than that in single block assessment (block 1: 20.3%, block 2: 20.9%) (P < 0.001). Conversely, dual block assessment demonstrated a lower HER2 negative (0/1+) rate (64.8%) than single block assessment (block1: 71.9%, block 2: 71.3%) (P < 0.001). These findings were also confirmed in individual hospitals.

Conclusions: Dual block HER2 assessment effectively increased HER2 IHC positive rate in resected specimens of GC. We recommended dual block HER2 assessment be promoted in routine clinical practice in GC.

Trial Registration: ClinicalTrials.gov, NCT02843412 . Registered 1 July 2016 - Retrospectively registered.
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http://dx.doi.org/10.1186/s13000-022-01230-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238183PMC
June 2022

Current opinions on diagnosis and treatment of adenoid cystic carcinoma.

Oral Oncol 2022 Jul 2;130:105945. Epub 2022 Jun 2.

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Anatomy Laboratory of Division of Nose and Cranial Base, Clinical Anatomy Center of Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address:

Adenoid cystic carcinoma (ACC) is a rare malignant tumor derived mainly from the salivary glands, representing approximately 1% of all headandneck carcinomasand 10% of all salivary gland neoplasms. ACC displays a paradoxical behavioral combination of an indolent growth pattern but an aggressive progression, with local recurrence and distant metastasis. The propensity of ACC of the head and neck (ACCHN) for perineural invasion and its anatomical location, especially if it extends to the nasal cavity and paranasal sinuses, facilitates tumor involvement in the surrounding structures, such as the orbit, pterygopalatine fossa, Meckel'scave, and cavernous sinus, which can lead to skull base involvement and intracranial extension. Despite advances in molecular mechanisms and diagnostic imaging, ACC treatment remainschallenging due to the lack ofconsensuson treatment patterns. In this review, we aimed toprovideanupdatedinsight intothe understanding of ACCHN by focusing on clinical behavior, imaging diagnosis, pathological features, and therapeutic strategies. We reviewed the molecular mechanisms, especially in ACCHN with perineural invasion, and elaborated on treatment options, including chemotherapy, targeted therapies, and immunotherapy, to establish a comprehensive understanding of ACC to arrive at a policy for proper diagnosis, preoperative evaluation, and therapeutic strategies.
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http://dx.doi.org/10.1016/j.oraloncology.2022.105945DOI Listing
July 2022

Early intervention of surrounding needling technique in the treatment of herpes zoster: a case report.

Acupunct Med 2022 Jun 3:9645284221086287. Epub 2022 Jun 3.

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

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http://dx.doi.org/10.1177/09645284221086287DOI Listing
June 2022

Electrochemical Behaviour and Chemical Species of Sm(II) in AlCl -NaCl with Different Lewis Acidity.

Chemistry 2022 Jul 16;28(42):e202200443. Epub 2022 Jun 16.

Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

AlCl -NaCl was utilized as an electrolyte in this work due to its low melting point and Lewis acidity, in which samarium exists in two oxidation states, Sm(III) and Sm(II), resulting in unique electrochemical behaviours. Sm metal dissolves in AlCl -NaCl melt to form SmCl , which is verified by electrochemical and spectroscopic techniques. As the Lewis acidity of the melt increases, the diffusion coefficient of Sm(II) gradually increases, and the activation energy of diffusion decreases. Moreover, an additional co-reduction peak of Sm and AlCl is observed to be more positive than that of Al(0)/Al(III) in Lewis basic melt, which may be tightly correlated with the variation of Sm(II) coordination in AlCl -NaCl melt and ligand variation from Cl to AlCl and Al Cl as the Lewis acidity of the AlCl -NaCl melt increases, according to the in situ electronic absorption spectra of Sm in this melt.
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http://dx.doi.org/10.1002/chem.202200443DOI Listing
July 2022

SP70 is a potential biomarker to identify gastric fundic gland neoplasms.

World J Surg Oncol 2022 Apr 25;20(1):132. Epub 2022 Apr 25.

Department of Pathology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Rd, Xuhui District, Shanghai, 200032, People's Republic of China.

Background: Gastric neoplasms with fundic gland differentiation include oxyntic gland adenomas (OGAs) and gastric adenocarcinomas of fundic gland type (GA-FGs). Due to their well-differentiated and similar morphology with normal fundic glands, it is usually challenging to identify these lesions in pathological diagnosis, especially in biopsy specimens. This study aims to explore and verify the potential role of a newly developed monoclonal antibody (McAb) NJ001 (SP70) in differentiating fundic neoplasms from non-neoplastic fundic gland lesions.

Methods: Twenty-three cases of histological confirmed gastric fundic gland neoplasms were obtained, including 12 cases of OGAs and 11 of GA-FGs. Fifty cases of fundic gland polyps (FGPs) were taken as the control group. Six cases of well-differentiated gastric neuroendocrine tumors (NETs) (easily misdiagnosed) were also obtained. Key clinicopathological information was collected. SP70 immunostaining was performed (with para-tumor normal fundic glands as internal control). The positive intensity and staining pattern of SP70 were analyzed and compared.

Results: In normal gastric mucosa, SP70 was strongly and diffusely stained on the cytoplasm in fundic glands, but not in the foveolar epithelium. Therefore, a zonal distribution of SP70 was observed in normal mucosa. FGPs (50/50, 100%) shared a similar expression pattern with normal fundic glands. In fundic gland neoplasms, a significant down-expression of SP70 was observed in both OGAs and GA-FGs. The positive rate of SP70 in fundic gland neoplasms (6/23, 26.1%) was significantly lower than that in FGPs (100%) (P<0.0001). There was no difference in SP70 expression between OGAs (3/12, 25.0%) and GA-FGs (3/11, 27.2%) group (P>0.05). In these 6 NET cases, SP70 was weak to moderate intensity in the majority of tumor cells (with a different expression pattern).

Conclusion: Down-expression of SP70 is a specific feature to fundic gland neoplasms including OGAs and GA-FGs. Therefore, SP70 can serve as a potential biomarker in the identification and differential diagnosis of fundic gland neoplasms.
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http://dx.doi.org/10.1186/s12957-022-02564-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036694PMC
April 2022

Chemical Species Transformation during the Dissolution Process of UO and UO in the LiCl-KCl-AlCl Molten Salt.

Inorg Chem 2022 May 15;61(17):6519-6529. Epub 2022 Apr 15.

Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

In this work, we investigated the dissolution behavior of UO and UO in the LiCl-KCl molten salt using 2.9 or 9.5 wt % AlCl as a chlorination agent under an argon atmosphere at 450 °C. Ultraviolet-visible/Ultraviolet-visible-near infrared absorption spectroscopy (UV-vis/UV-vis-NIR), fluorescence emission spectroscopy (FL), X-ray absorption fine structure (XAFS), and electrochemical techniques were used to systematically study the chemical species and the transformation of the dissolved products of UO and UO. It was found that with the aid of AlCl, the initial products of UO and UO dissolution were different. The initial products of UO were UOCl and UCl, while the initial product of UO dissolution was UOCl. Interestingly, regardless of UO or UO, with the increase of AlCl content, the UOCl in their dissolved products showed a tendency to transform into UCl. In addition, UCl was produced by mixing 0.05 g of UO/UO powders with 10 times the amount of AlCl and heating them at 300 °C for 2 h. This work focuses on the pyrochemical reprocessing of spent oxide fuels, deepening the understanding of the dissolution of uranium oxides in higher oxidation states, and enriching the knowledge of uranium in the transformation of chemical species in molten salts.
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http://dx.doi.org/10.1021/acs.inorgchem.2c00286DOI Listing
May 2022

Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).

Front Immunol 2022 17;13:865401. Epub 2022 Mar 17.

Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.

Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.
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http://dx.doi.org/10.3389/fimmu.2022.865401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967979PMC
March 2022

Municipal solid waste incineration (MSWI) ash co-disposal: Influence on per- and polyfluoroalkyl substances (PFAS) concentration in landfill leachate.

Waste Manag 2022 May 17;144:49-56. Epub 2022 Mar 17.

University of Florida, Department of Environmental Engineering Sciences, College of Engineering, Gainesville, FL 32611, USA. Electronic address:

Municipal solid waste incineration (MSWI) ash is often managed through co-disposal with unburned wastes in landfills, a practice previously reported to result in enhanced leaching of pollutants (e.g., heavy metals) in landfill leachate. The objective of this study was to evaluate the effect of co-disposed unburned wastes on per- and polyfluoroalkyl substances (PFAS) in MSWI ash landfill leachate. Leachate was collected from four landfills containing MSWI ash, either as a sole waste stream or co-disposed of with sewage sludge and MSW screenings. Samples of ash and unburned materials were collected and assessed separately for leachable PFAS in the laboratory. All samples were analyzed for 26 PFAS. Results showed that greater ash content was associated with lower leachate PFAS concentrations. The pure ash monofill exhibited the lowest PFAS in landfill leachate (290 ng L) while the landfill contained a large amount of unburned waste had the highest PFAS (11,000 ng L). For laboratory leaching tests, average ∑PFAS concentration in lab ash leachate (310 ng L) was 10 and 24 times lower than observed in lab sewage sludge leachate (3,200 ng L) and lab MSW screenings leachate (7,500 ng L), respectively. Leachate from the ash-only landfill had ∑PFAS concentration similar to what was measured in the ash itself. On the contrary, ∑PFAS concentration in co-disposal landfill leachates were similar to those in PFAS-rich unburned waste itself, regardless of the percentages of landfilled unburned wastes. We hypothesize that leachate generated in co-disposal scenarios preferentially flows through PFAS-rich unburned materials and that biotransformation of precursors enhanced by unburned waste degradation further contributes to higher concentrations of terminal PFAS in ash co-disposal sites. Landfill operators should expect PFAS in leachates to be higher when PFAS-rich unburned wastes are disposed of alongside MSWI ash, even if the unburned fraction is small.
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http://dx.doi.org/10.1016/j.wasman.2022.03.009DOI Listing
May 2022

Evaluation of anthropometric indices as a predictor of diabetes in Dong and Miao ethnicities in China: A cross-sectional analysis of China Multi-Ethnic Cohort Study.

PLoS One 2022 11;17(3):e0265228. Epub 2022 Mar 11.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Guizhou Medical University, Ministry of Education, Guiyang, China.

Background: Although it is known that obesity is inseparable from diabetes, many anthropometric indices are used for determining obesity. At the same time, research on the predictive indices of diabetes in Chinese minority populations is lacking. Therefore, this study determines the relationship between different anthropometric indices and diabetes, and identifies the best index and best cut-off values for predicting diabetes.

Method: In total, 11,035 Dong and Miao ethnic participants (age: 30-79 years) from the China Multi-Ethnic Cohort study were included. The logistic regression model was used to examine the relationship between the different anthropometric indices and diabetes risk. The receiver operating characteristic curve and the area under the curve (AUC) were used to identify the best predictor of diabetes.

Results: In multivariate adjusted logistic regression models, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI) were positively correlated with diabetes risk. Among Chinese Dong men and women and Miao men, WHR had the largest AUC (0.654/0.719/0.651). Among Miao women, VAI had the largest AUC(0.701). The best cut-off values of WHR for Dong men and women and Miao men were 0.94, 0.92, and 0.91, respectively. The best cut-off value of VAI for Miao women was 2.20.

Conclusion: Obesity indicators better predict diabetes in women than men. WHR may be the best predictor of diabetes risk in both sex of Dong ethnicity and Miao men, and VAI may be the best predictor of diabetes risk in Miao women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0265228PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8916665PMC
May 2022

Retrospective analysis of the risk factors associated with failure in obtaining effective noninvasive prenatal test results and pregnancy outcomes: a case-control study.

Expert Rev Mol Diagn 2022 03 9;22(3):387-394. Epub 2022 Mar 9.

Department of Otolaryngology Heard and Neck Surgery, Xiangya Hospital, Central South University, Changsha Hunan, China.

Objective: To explore the pregnancy outcomes of women who couldn't obtain effective results from noninvasive prenatal testing (NIPT) and examine the factors leading to test failure.

Methods: From April 2017 to December 2019, 120,041 pregnant women enrolled for voluntary NIPT. The case group comprised of 274 (274/120,041) women who failed to obtain effective NIPT results, and the control group ( = 540) was from the same population who obtained effective NIPT results and matched by age at a 1:2 ratio. Abnormal pregnancy rates between the two groups were analyzed using Chi-square analysis. NIPT failure risk factors were analyzed using logistic regression analysis.

Results: Logistic regression analysis showed that increased maternal age (OR = 0.988; 95% CI = 0.982-0.994), increased pregnancy age (OR = 0.989; 95%CI = 0.988-0.991), and decreased cell-free fetal DNA concentration (OR = 1.050; 95%CI = 1.043-1.058) were independent risk factors for NIPT failure. Fifteen cases showed fetus loss in cases of NIPT failure. There was a significant difference in abnormal pregnancy rate between the NIPT success and failure groups (χ2 = 50.943, P < 0.05).

Expert Commentary: The specific interventions, guidance, and precautions are needed for pregnant women who have no effective NIPT results.
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http://dx.doi.org/10.1080/14737159.2022.2049245DOI Listing
March 2022

The assessment of spirituality between cancer and chronic inpatients: a cross-sectional study.

Support Care Cancer 2022 May 26;30(5):4157-4167. Epub 2022 Jan 26.

Department of Quality Control, Chongqing University, Three Gorges Hospital/Chongqing Three Gorges Central Hospital, Chongqing, China.

Purpose: Spiritual well-being had a protective effect on quality of life in cancer, due to the cultural, regional, and custom differences; it was rarely been discussed between cancer and chronic diseases in Chongqing, China. We aimed at comparing the level of spirituality in two groups and discussing its factors of subjects with cancer at county regions.

Methods: A cross-sectional questionnaire survey was distributed to 630 inpatients who received treatment between January and December 2020 in Chongqing University Three Gorges Hospital. In addition to basic demographic data, spirituality was measured using the Chinese version of Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12). The mean, standard deviation, independent t-tests, ANOVA, and multiple regression were used for statistical description and analysis.

Results: Significant differences were found between cancer and chronic diseases in total scores of FACIT-Sp-12 and each domain (P < 0.05). The meaning, peace, faith, and total scores in cancer were 11.21 ± 3.38, 10.66 ± 4.46, 11.43 ± 3.54, and 33.3 ± 10.35, respectively, which were lower than chronic diseases (13.00 ± 3.21, 12.95 ± 4.76, 12.66 ± 3.64, 38.61 ± 10.88, respectively). The spiritual well-being had significant differences in gender, character, and emotional with spouse for cancer (P < 0.05). The male and extravert character were significantly associated with a greater spiritual well-being.

Conclusion: The study shows a medium level of spiritual well-being in cancer, which stands the population with lower economic and education in county regions. It suggests that under the current nursing mode, we should provide specifically spiritual care to the female, introvert, and those with poor relationship with spouses and create a harmonious doctor-patient environment to improve the spiritual well-being.
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http://dx.doi.org/10.1007/s00520-022-06847-4DOI Listing
May 2022

Cell-Free DNA Screening for Sex Chromosome Abnormalities and Pregnancy Outcomes, 2018-2020: A Retrospective Analysis.

J Pers Med 2022 Jan 4;12(1). Epub 2022 Jan 4.

Department of Otolaryngology Heard and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008, China.

To evaluate the efficacy of non-invasive prenatal screening (NIPT) for detecting fetal sex chromosome abnormalities, a total of 639 women carrying sex chromosome abnormalities were selected from 222,107 pregnant women who participated in free NIPT from April 2018 to December 2020. The clinical data, prenatal diagnosis results, and follow-up pregnancy outcomes of participants were collected. The positive predictive value (PPV) was used to analyze the performance of NIPT. Around 235 cases were confirmed with sex chromosome abnormalities, including 229 cases with sex chromosome aneuploidy (45, X ( = 37), 47, XXX ( = 37), 47, XXY ( = 110), 47, XYY ( = 42)) and 6 cases with structural abnormalities. The total incidence rate was 0.11% (235/222,107). The PPV of NIPT was 45.37% (235/518). NIPT accuracy for detecting sex chromosome polysomes was higher than that for sex chromosome monomers. The termination of pregnancy rate for fetal diagnosis of 45, X, and 47, XXY was higher than that of 47, XXX, and 47, XYY. The detection rate of fetal sex chromosome abnormalities was higher in 2018-2020 than in 2010-2012 (χ = 69.708, < 2.2 × 10), indicating that NIPT is greatly efficient to detect fetal sex chromosome abnormalities.
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http://dx.doi.org/10.3390/jpm12010048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780735PMC
January 2022

Effects of short-term nitrogen and phosphorus addition on leaf stoichiometry of a dominant alpine grass.

PeerJ 2021 22;9:e12611. Epub 2021 Dec 22.

Xinjiang Key Laboratory of Desert Plant Roots Ecology and Vegetation Restoration, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi, China.

The effects of increasing nitrogen (N) and phosphorus (P) deposition on the nutrient stoichiometry of soil and plant are gaining improving recognition. However, whether and how the responses of N cycle coupled with P of the soil-plant system to external N and P deposition in alpine grassland is still unclear. A short-term external N and P addition experiment was conducted in an alpine grazing grassland in the KunLun Mountain to explore the effects of short-term N and P addition on the nutrient stoichiometry in soil and plant. Different rates of N addition (ranging from 0.5 g N m yr to 24 g N m yr) and P addition (ranging from 0.05 g N m yr to 3.2 g P m yr) were supplied, and the soil available N, P, leaf N and P stoichiometry of which dominant in the alpine ecosystem were measured. Results showed that N addition increased soil inorganic N, leaf C, leaf N, and leaf N:P ratio but decreased soil available P and leaf C:P. Furthermore, P addition increased soil available P, leaf P, soil inorganic N, leaf N, and leaf C and reduced leaf C:N, C:P, and N:P ratios. Leaf N:P was positively related to N addition gradient. Leaf C:P and leaf N:P were significantly negatively related to P addition gradient. Although external N and P addition changed the value of leaf N:P, the ratio was always lower than 16 in all treatments. The influences of P addition on soil and plant mainly caused the increase in soil available P concentration. In addition, the N and P cycles in the soil-plant system were tightly coupled in P addition but decoupled in N addition condition. The nutrient stoichiometry of soil and leaf responded differently to continuous N and P addition gradients. These data suggested that the alpine grazing grassland was limited by P rather than N due to long-term N deposition and uniform fertilization. Moreover, increasing P addition alleviated P limitation. Therefore, the imbalanced N and P input could change the strategy of nutrient use of the grass and then change the rates of nutrient cycling in the alpine grassland ecosystem in the future.
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http://dx.doi.org/10.7717/peerj.12611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710051PMC
December 2021

Discriminating invasive adenocarcinoma among lung pure ground-glass nodules: a multi-parameter prediction model.

J Thorac Dis 2021 Sep;13(9):5383-5394

Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Patients with consistent lung pure ground-glass nodules (pGGNs) have a high incidence of lung adenocarcinoma that can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Regular follow-up is recommended for AIS and MIA, while surgical resection should be considered for IAC. This study sought to develop a multi-parameter prediction model to increase the diagnostic accuracy in discriminating between IAC and AIS or MIA.

Methods: The training data set comprised consecutive patients with lung pGGNs who underwent resection from January to December 2017 at the Zhongshan Hospital. Of the 370 resected pGGNs, 344 were pathologically confirmed to be AIS, MIA, or IAC and were included in the study. The 26 benign pGGNs were excluded. We compared differences in the clinical features (e.g., age and gender), the content of serum tumor biomarkers, the computed tomography (CT) parameters (e.g., nodule size and the maximal CT value), and the morphologic characteristics of nodules (e.g., lobulation, spiculation, pleura indentation, vacuole sign, and normal vessel penetration or abnormal vessel) between the pathological subtypes of AIS, MIA, and IAC. An abnormal vessel was defined as "vessel curve" or "vessel enlargement". Statistical analyses were performed using the chi-square test, analysis of variance (ANOVA), and rank test. The IAC prediction model was constructed via a multivariate logistical regression. Our prediction model for lung pGGNs was further validated in a data set comprising consecutive patients from multiple medical centers in China from July to December 2018. In total, 345 resected pGGNs were pathologically diagnosed as lung adenocarcinoma in the validation data set.

Results: In the training data set, patients with pGGNs ≥10 mm in size had a high incidence (74.5%) of IAC. The maximal CT value of IAC [-416.1±121.2 Hounsfield unit (HU)] was much higher than that of MIA (-507.7±138.0 HU) and AIS (-602.6±93.3 HU) (P<0.001). IAC was more common in pGGNs that displayed any of the following CT manifestations: lobulation, spiculation, pleura indentation, vacuole sign, and vessel abnormality. The IAC prediction model was constructed using the parameters that were assessed as risk factors (i.e., the nodule size, maximal CT value, and CT signs). The receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this model for diagnosing IAC was 0.910, which was higher than that of the AUC for nodule size alone (0.891) or the AUC for the maximal CT value alone (0.807) (P<0.05, respectively). A multicenter validation data set was used to validate the performance of our prediction model in diagnosing IAC, and our model was found to have an AUC of 0.883, which was higher than that of the AUC of 0.827 for the module size alone model or the AUC of 0.791 for the maximal CT value alone model (P<0.05, respectively).

Conclusions: Our multi-parameter prediction model was more accurate at diagnosing IAC than models that used only nodule size or the maximal CT value alone. Thus, it is an efficient tool for identifying the IAC of malignant pGGNs and deciding if surgery is needed.
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http://dx.doi.org/10.21037/jtd-21-786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482342PMC
September 2021

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration.

Cell Rep 2021 10 6;37(3):109869. Epub 2021 Oct 6.

School of Life Sciences, Ningxia University, Yinchuan, People's Republic of China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, People's Republic of China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, People's Republic of China. Electronic address:

The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb-Nb-Nb, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb-Nb-Nb exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb-Nb-Nb provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb-Nb-Nb is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.
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http://dx.doi.org/10.1016/j.celrep.2021.109869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492916PMC
October 2021

HER2 promotes epithelial-mesenchymal transition through regulating osteopontin in gastric cancer.

Pathol Res Pract 2021 Nov 5;227:153643. Epub 2021 Oct 5.

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Pathology, School of Basic Medical Sciences & Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

Aims: HER2 and osteopontin (OPN) are both important biomarkers in gastric cancer (GC). The relationships between them remain to be revealed. The purpose of this study is to explore the role of OPN in epithelial-mesenchymal transition (EMT) in HER2 positive GCs.

Methods: Nanostring analysis was used to compare the mRNA levels of 730 cancer related genes between paired HER2 3+ and non-3+ areas in GC patients. Immunohistochemistry (IHC) staining was performed to analyze the expression levels of OPN, as well as EMT markers including E-cad, N-cad, twist and vimentin in both areas. To further verify the role of OPN in EMT, the expression levels of OPN and EMT markers, tumor invasion/migration were analyzed after down-regulating HER2 and OPN in GC cell lines MKN-45 and N-87.

Results: Nanostring analysis identified 8 differential expression genes between HER2 3+ and non-3+ areas. Among them, the expression level of OPN was positively correlated with that of HER2. In GC specimens, OPN showed higher expression level in HER2 3+ areas where higher E-cad expression levels and lower N-cad and twist levels were also found. After knocking down OPN and HER2 by siRNA, both cell lines show decreased invasion/migration abilities, along with the down-regulation of the EMT phenotype, supporting by the decrease of E-cad, and the increase of N-cad and twist at both mRNA and protein levels. In addition, HER2 knock-down lead to a dramatic decrease of OPN expression.

Conclusions: These findings indicate that HER2 may promote EMT via the regulation of OPN in GCs.
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http://dx.doi.org/10.1016/j.prp.2021.153643DOI Listing
November 2021

Neuroimaging Studies of Acupuncture on Low Back Pain: A Systematic Review.

Front Neurosci 2021 20;15:730322. Epub 2021 Sep 20.

Acupuncture and Tuina School, Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

This study was conducted in order to investigate the study design and main outcomes of acupuncture neuroimaging studies on low back pain (LBP). Neuroimaging studies of acupuncture on LBP were collected from three English databases such as PubMed and four Chinese databases such as China National Knowledge Infrastructure (CNKI) from inception to December 31, 2020. Study selection, data extraction, and assessment of risk of bias were performed independently by two investigators. The quality of studies was appraised with the Cochrane's risk of bias tools. Information on basic information, methodology, and brain imaging data were extracted. The literature search returned 310 potentially eligible studies and 19 articles met inclusion criteria; 78.9% of studies chose manual acupuncture as the intervention, 89.5% of studies evaluated functional changes elicited by acupuncture, and 68.4% of studies used resting-state fMRI as imaging condition. The most frequently reported acupuncture-induced brain alterations of LBP patients were in the prefrontal cortex, insula, cerebellum, primary somatosensory cortex, and anterior cingulate cortex. There was a significant correlation between improved clinical outcomes and changes in the brain. The results suggested that improving abnormal structure and functional activities in the brain of the LBP patient is an important mechanism of acupuncture treatment for LBP. The brain regions involved in acupuncture analgesia for LBP were mainly located in the pain matrix, default mode network (DMN), salience network (SN), and descending pain modulatory system (DPMS). However, it was difficult to draw a generalized conclusion due to the heterogeneity of study designs. Further well-designed multimodal neuroimaging studies investigating the mechanism of acupuncture on LBP are warranted.
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http://dx.doi.org/10.3389/fnins.2021.730322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488100PMC
September 2021

Acupuncture for chronic persistent asthma: a case report.

Acupunct Med 2022 02 19;40(1):106-108. Epub 2021 Sep 19.

Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

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http://dx.doi.org/10.1177/09645284211040086DOI Listing
February 2022

Rare NRXN1 missense variants identified in autism interfered protein degradation and Drosophila sleeping.

J Psychiatr Res 2021 11 2;143:113-122. Epub 2021 Sep 2.

Center for Medical Genetics and Hunan Provincial Key Laboratory for Medical Genetics, School of Life Sciences, Central South University, Changsha, China; CAS Center for Excellence in Brain Science and Intelligences Technology (CEBSIT), Shanghai, China; Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan, China. Electronic address:

NRXN1 is involved in synaptogenesis and have been implicated in Autism spectrum disorders. However, many rare inherited missense variants of NRXN1 have not been thoroughly evaluated. Here, functional analyses in vitro and in Drosophila of three NRXN1 missense mutations, Y282H, L893V, and I1135V identified in ASD patients in our previous study were performed. Our results showed these three mutations interfered protein degradation compared with NRXN1-WT protein. Expressing human NRXN1 in Drosophila could lead to abnormal circadian rhythm and sleep behavior, and three mutated proteins caused milder phenotypes, indicating the mutations may change the function of NRXN1 slightly. These findings highlight the functional role of rare NRXN1 missense variants identified in autism patients, and provide clues for us to better understand the pathogenesis of abnormal circadian rhythm and sleep behavior of other organisms, including humans.
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http://dx.doi.org/10.1016/j.jpsychires.2021.09.013DOI Listing
November 2021

A Model of Waardenburg Syndrome Using Patient-Derived iPSCs With a Mutation Displays Compromised Maturation and Function of the Neural Crest That Involves Inner Ear Development.

Front Cell Dev Biol 2021 6;9:720858. Epub 2021 Aug 6.

Department of Otorhinolaryngology, Xiangya Hospital Central South University, Changsha, China.

Waardenburg syndrome (WS) is an autosomal dominant inherited disorder that is characterized by sensorineural hearing loss and abnormal pigmentation. is one of its main pathogenicity genes. The generation of patient-specific induced pluripotent stem cells (iPSCs) is an efficient means to investigate the mechanisms of inherited human disease. In our work, we set up an iPSC line derived from a WS patient with mutation and differentiated into neural crest cells (NCCs), a key cell type involved in inner ear development. Compared with control-derived iPSCs, the mutant iPSCs showed significantly decreased efficiency of development and differentiation potential at the stage of NCCs. After that, we carried out high-throughput RNA-seq and evaluated the transcriptional misregulation at every stage. Transcriptome analysis of differentiated NCCs showed widespread gene expression alterations, and the differentially expressed genes (DEGs) were enriched in gene ontology terms of neuron migration, skeletal system development, and multicellular organism development, indicating that has a pivotal part in the differentiation of NCCs. It's worth noting that, a significant enrichment among the nominal DEGs for genes implicated in inner ear development was found, as well as several genes connected to the inner ear morphogenesis. Based on the protein-protein interaction network, we chose four candidate genes that could be regulated by in inner ear development, namely, , , , and . In conclusion, SOX10 deficiency in this WS subject had a significant impact on the gene expression patterns throughout NCC development in the iPSC model. The DEGs most significantly enriched in inner ear development and morphogenesis may assist in identifying the underlying basis for the inner ear malformation in subjects with WS.
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http://dx.doi.org/10.3389/fcell.2021.720858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379019PMC
August 2021

A comparative study of the RuiBreath and NIOX VERO analyzers for detecting fractional exhaled nitric oxide.

J Thorac Dis 2021 Jul;13(7):4418-4426

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Background: Fractional exhaled nitric oxide (FeNO) measurement is a reliable, noninvasive marker of airway inflammation. Portable FeNO analyzers facilitate the assessment of airway inflammation in primary care. Differences between analyzers from different manufacturers are not comparable. Here, we aimed to compare the FeNO values obtained by a new portable device (RuiBreath, Guangzhou Ruipu Medical Technology Co., Ltd, Guangzhou, China) to those obtained by the widely used NIOX VERO portable analyzer (Aerocrine AB, Solna, Sweden) in patients with asthma.

Methods: This prospective validation study enrolled patients (≥14 years old) with asthma over a 2-month period (July and August 2019) at the Beijing Chao-Yang Hospital. At least one valid FeNO measurement was obtained using each analyzer for all the participants.

Results: There were 197 participants in this study. The FeNONIOX and FeNORuiBreath values significantly differed (P=0.016). After log-transformation, a difference was found only when the FeNONIOX was <25 ppb (P<0.001). The FeNONIOX and FeNORuiBreath values had a significant correlation (r=0.938, P<0.001), which was confirmed by the Altman-Bland plot. Using a receiver-operating characteristic curve analysis, when using 49 ppb as the cut-off point for the two devices in identifying patients with symptomatic asthma symptoms, the sensitivity and specificity were 0.42 and 0.88, respectively, by NIOX, and 0.40 and 0.89, respectively, by RuiBreath.

Conclusions: This is the first report of FeNO values obtained by the new portable RuiBreath FeNO analyzer. The FeNORuiBreath values are reliable and directly comparable with the FeNONIOX values.
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http://dx.doi.org/10.21037/jtd-21-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339745PMC
July 2021

Human Norovirus NTPase Antagonizes Interferon-β Production by Interacting With IkB Kinase ε.

Front Microbiol 2021 15;12:687933. Epub 2021 Jul 15.

State Key Laboratory of Virology, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.

Human norovirus (HuNoV) is the leading cause of epidemic acute gastroenteritis worldwide. Type I interferons (IFN)-α/β are highly potent cytokines that are initially identified for their essential roles in antiviral defense. It was reported that HuNoV infection did not induce IFN-β expression but was controlled in the presence of IFN-β in human intestinal enteroids and a gnotobiotic pig model, suggesting that HuNoV has likely developed evasion countermeasures. In this study, we found that a cDNA clone of GII.4 HuNoV, the predominantly circulating genotype worldwide, inhibits the production of IFN-β and identified the viral NTPase as a key component responsible for such inhibition. HuNoV NTPase not only inhibits the activity of IFN-β promoter but also the mRNA and protein production of IFN-β. Additional studies indicate that NTPase inhibits the phosphorylation and nuclear translocation of interferon-regulatory factor-3 (IRF-3), leading to the suppression of IFN-β promoter activation. Mechanistically, NTPase interacts with IkB kinase ε (IKKε), an important factor for IRF-3 phosphorylation, and such interaction blocks the association of IKKε with unanchored K48-linked polyubiquitin chains, resulting in the inhibition of IKKε phosphorylation. Further studies demonstrated that the 1-179 aa domain of NTPase which interacts with IKKε is critical for the suppression of IFN-β production. Our findings highlight the role of HuNoV NTPase in the inhibition of IFN-β production, providing insights into a novel mechanism underlying how HuNoV evades the host innate immunity.
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http://dx.doi.org/10.3389/fmicb.2021.687933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319745PMC
July 2021

Analysis of Threshold Effect of Urinary Heavy Metal Elements on the High Prevalence of Nephrolithiasis in Men.

Biol Trace Elem Res 2022 Mar 14;200(3):1078-1088. Epub 2021 Jul 14.

School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 550025, China.

Exposure to heavy metals in the environment exerts serious effects on kidney health. However, the effects of joint exposure on the kidneys have been rarely studied, particularly in non-occupational exposure high-risk populations. This study provided a reference threshold range of heavy metals in urine and explored the effect of joint exposure on nephrolithiasis in men. The data were obtained from the China Multi-Ethnic Cohort database, and 1502 men were included in the study. A two-piece-wise regression model was used to assess the dose-response relationship between heavy metal exposure and nephrolithiasis. The least absolute shrinkage and selection operator regression model was used to calculate the score of joint exposure to heavy metals. The threshold effect analysis revealed a linear relationship between the concentration of arsenic (As) in the urine and the prevalence of nephrolithiasis, whereas a nonlinear relationship was observed with cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). In addition, As, Cd, Cr, Hg, and Pb may significantly affect the joint exposure effect. Moreover, the final risk of nephrolithiasis increased by 123% (P for trend < 0.001). This study found a threshold relationship between heavy metals (Cd, Cr, Hg, Pb) in male urine and the occurrence of nephrolithiasis. Joint exposure to heavy metals in urine caused a high-risk effect on nephrolithiasis. The study provided a reference threshold value of related studies and indicated that environmental pollution caused by heavy metals should be reduced.
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http://dx.doi.org/10.1007/s12011-021-02740-zDOI Listing
March 2022

The genomic architectures of tumour-adjacent tissues, plasma and saliva reveal evolutionary underpinnings of relapse in head and neck squamous cell carcinoma.

Br J Cancer 2021 09 6;125(6):854-864. Epub 2021 Jul 6.

Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Background: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse.

Methods: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis.

Results: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse.

Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use.
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http://dx.doi.org/10.1038/s41416-021-01464-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438056PMC
September 2021

Competitive Coordination of Chloride and Fluoride Anions Towards Trivalent Lanthanide Cations (La and Nd ) in Molten Salts.

Chemistry 2021 Aug 5;27(45):11721-11729. Epub 2021 Jul 5.

Laboratory of Nuclear Energy Chemistry, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

Molten salt electrolysis is a vital technique to produce high-purity lanthanide metals and alloys. However, the coordination environments of lanthanides in molten salts, which heavily affect the related redox potential and electrochemical properties, have not been well elucidated. Here, the competitive coordination of chloride and fluoride anions towards lanthanide cations (La and Nd ) is explored in molten LiCl-KCl-LiF-LnCl salts using electrochemical, spectroscopic, and computational approaches. Electrochemical analyses show that significant negative shifts in the reduction potential of Ln occur when F concentration increases, indicating that the F anions interact with Ln via substituting the coordinated Cl anions, and confirm [LnCl F ] (y =3) complexes are prevailing in molten salts. Spectroscopic and computational results on solution structures further reveal the competition between Cl and F anions, which leads to the formation of four distinct Ln(III) species: [LnCl ] , [LnCl F] , [LnCl F ] and [LnCl F ] . Among them, the seven-coordinated [LnCl F ] complex possesses a low-symmetry structure evidenced by the pattern change of Raman spectra. After comparing the polarizing power (Z/r) among different metal cations, it was concluded that Ln-F interaction is weaker than that between transition metal and F ions.
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http://dx.doi.org/10.1002/chem.202101505DOI Listing
August 2021

Herpes Simplex Virus Type 2 Glycoprotein D Inhibits NF-κB Activation by Interacting with p65.

J Immunol 2021 06 28;206(12):2852-2861. Epub 2021 May 28.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China;

NF-κB plays a crucial role in regulating cell proliferation, inflammation, apoptosis, and immune responses. HSV type 2 (HSV-2) is one of the most predominant sexually transmitted pathogens worldwide, and its infection increases the risk of HIV type 1 (HIV-1) acquisition and transmission. HSV-2 glycoprotein D (gD), highly homologous to HSV-1 gD, is essential for viral adhesion, fusion, entry, and spread. It is known that HSV-1 gD can bind herpesvirus entry mediator (HVEM) to trigger NF-κB activation and thereby facilitate viral replication at the early stage of infection. In this study, we found that purified HSV-2 gD triggered NF-κB activation at the early stage of infection, whereas ectopic expression of HSV-2 gD significantly downregulated TNF-α-induced NF-κB activity as well as TNF-α-induced IL-6 and IL-8 expression. Mechanistically, HSV-2 gD inhibited NF-κB, but not IFN-regulatory factor 3 (IRF3), activation and suppressed NF-κB activation mediated by overexpression of TNFR-associated factor 2 (TRAF2), IκB kinase α (IKKα), IKKβ, or p65. Coimmunoprecipitation and binding kinetic analyses demonstrated that HSV-2 gD directly bound to the NF-κB subunit p65 and abolished the nuclear translocation of p65 upon TNF-α stimulation. Mutational analyses further revealed that HSV-2 gD interacted with the region spanning aa 19-187 of p65. Findings in this study together demonstrate that HSV-2 gD interacts with p65 to regulate p65 subcellular localization and thereby prevents NF-κB-dependent gene expression, which may contribute to HSV-2 immune evasion and pathogenesis.
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http://dx.doi.org/10.4049/jimmunol.2001336DOI Listing
June 2021

Antifibrotic Role of Nintedanib in Tracheal Stenosis After a Tracheal Wound.

Laryngoscope 2021 09 17;131(9):E2496-E2505. Epub 2021 May 17.

Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, China.

Objectives/hypothesis: Tracheal stenosis is an obstructive disease of the upper airway that commonly develops as a result of abnormal wound healing. We evaluated the anti-inflammatory and antifibrotic properties of nintedanib on tracheal stenosis both in vitro and in vivo.

Study Design: Prospective controlled animal study and in vitro comparative study of human cells.

Methods: An animal model of tracheal stenosis was induced via tracheal trauma. Postsurgical rats were orally administered with nintedanib (10 or 20 mg/kg/d) or saline (negative control) for 2 weeks, and tracheal specimens were harvested after 3 weeks. Degree of stenosis, collagen deposition, fibrotic surrogate markers expression, and T-lymphocytic infiltration were evaluated. Human fetal lung fibroblast-1 (HFL-1) cells were cultured to determine the effects of nintedanib on changes of cellular biological function induced by transforming growth factor-β1 (TGF-β1).

Results: Rat tracheal stenotic tissues exhibited thickened lamina propria with irregular epithelium, characterized by significantly increased collagen deposition and elevated TGF-β1, collagen I, α-SMA and fibronectin expressions. Nintedanib markedly attenuated the tracheal stenotic lesions, reduced the collagen deposition and the expression of fibrotic marker proteins, and mitigated CD4+ T-lymphocyte infiltration. Additionally, cellular proliferation and migration were decreased dose-dependently in TGF-β1-stimulated HFL-1 cells when treated with nintedanib. Furthermore, nintedanib inhibited TGF-β1-induced HFL-1 differentiation and reduced the mRNA levels of the profibrotic genes. TGF-β1-activated phosphorylation of the TGF-β/Smad2/3 and ERK1/2 pathways were also blocked by nintedanib.

Conclusion: Nintedanib effectively prevented tracheal stenosis in rats by inhibiting fibrosis and inflammation. The antifibrotic effect of nintedanib may be achieved by inhibiting fibroblasts' proliferation, migration and differentiation and suppressing the TGF-β1/Smad2/3 and ERK1/2 signaling pathways.

Level Of Evidence: NA Laryngoscope, 131:E2496-E2505, 2021.
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http://dx.doi.org/10.1002/lary.29618DOI Listing
September 2021

Correlation between ground-glass opacity on pulmonary CT and the levels of inflammatory cytokines in patients with moderate-to-severe COVID-19 pneumonia.

Int J Med Sci 2021 16;18(11):2394-2400. Epub 2021 Apr 16.

Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, P.R. China.

Comparative analysis of laboratory data in moderate-to-severe COVID-19 patients presenting with or without ground-glass opacities (GGOs). This retrospective study examined 61 patients with moderate-to-severe COVID-19, as defined by the report of the WHO-China Joint Mission on COVID-19. All patients were admitted to the Department of Infectious Diseases, Wuhan Union Hospital from Dec 28, 2019 to Feb 22, 2020 and classified into a GGO group or a non-GGO group based on CT results. The clinical characteristics and laboratory data of the two groups were compared. Data were analyzed using univariate and multivariate analysis, and using receiver operating characteristic (ROC) analysis. Forty-five patients were in the GGO group (73.8%, 21 females, 24 males, mean age 54.8±17.8 years) and 16 were in the non-GGO group (26.2%, 11 females, 5 males, mean age 53±14.9 years). The levels of IL-2, IL-4, and IFN-γ were greater in the GGO group (all P<0.05). ROC analysis indicated that an elevated level of IL-2 was a good predictor of GGO (area under the curve: 0.716, optimal cutoff: 3.205 pg/mL, 53.8% sensitivity, 87.5% specificity, p<0.05). Multivariate analysis showed that IL-2 level was a significant and independent risk factor for lung GGO (OR: 8.167; 95% CI: 1.63, 40.8; P<0.05). There were correlations between GGO in the lungs of patients with moderate-to-severe COVID-19 and the levels of IL-2, IL-4, and INF-γ. IL-2 was a significant and independent risk factor for GGO. These findings provide a basis for studying the mechanism of pulmonary lesions in COVID-19 patients.
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http://dx.doi.org/10.7150/ijms.56683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100652PMC
May 2021
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