Publications by authors named "Yan Zheng"

1,316 Publications

  • Page 1 of 1

The Level of D-Dimer Is Positively Correlated With the Severity of Pneumonia in Children.

Front Cell Infect Microbiol 2021 15;11:687391. Epub 2021 Jul 15.

Department of Pulmonology, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Objective: pneumonia (MPP) is an important disease in children. Studies have demonstrated that the levels of D-dimer are elevated in some children with MPP, especially those with thrombotic complications. However, the potential association between MPP and D-dimer remains unclear. In our study, we sought to explore the relationship between the levels of plasma D-dimer and clinical characteristics of MPP patients.

Methods: Retrospective analysis was conducted on 356 patients who were hospitalized in our hospital for MPP between January 1, 2017, and December 31, 2019. According to the peak value of D-dimer, patients were divided into three groups: the normal group (D-dimer<0.55 mg/L), the mild-moderately elevated group (D-dimer 0.55-5.5 mg/L) and the severely elevated group (D-dimer >5.5 mg/L). The demographic and clinical information, radiological findings, laboratory data, and treatments of patients were compared among different groups.

Results: 106 patients were in the normal group, 204 patients were in the mild-moderately elevated group, and 46 patients were in the severely elevated group. More severe clinical and radiographic manifestations, longer length of fever, hospital stay and antibiotic therapy duration, higher incidences of extra-pulmonary complications, refractory MPP (RMPP), severe MPP (SMPP) were found in the elevated group, when compared with the normal group (<0.01). Meanwhile, we found that the percentage of neutrophil (N%) and CD lymphocyte (CD %), C-reactive protein (CRP), lactate dehydrogenase (LDH), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ) trended higher with increasing D-dimer, whereas the percentage of lymphocyte (L%) and prealbumin (PAB) trended lower (<0.01). In addition, the proportions of patients requiring oxygen therapy, glucocorticoid, bronchoscopy, immunoglobulin use, thoracentesis, or ICU admission were significantly higher in the severely elevated group than those in the other two groups (<0.01). Correlation analysis showed that N%, L%, CRP, LDH, IL-10, length of fever, length of stay, and length of antibiotic therapy had strong correlations with the level of D-dimer.

Conclusions: MPP patients with higher levels of D-dimer had more severe clinical manifestations and needed longer duration of treatment, which might be closely related to the severity of lung inflammation after MP infection.
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http://dx.doi.org/10.3389/fcimb.2021.687391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319762PMC
July 2021

The Risk of Immune-Related Thyroid Dysfunction Induced by PD-1/PD-L1 Inhibitors in Cancer Patients: An Updated Systematic Review and Meta-Analysis.

Front Oncol 2021 12;11:667650. Epub 2021 Jul 12.

Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.

Background: Thyroid dysfunction is common for cancer patients receiving PD-1/PD-L1 inhibitor therapies. To clarify the incidence risk of thyroid dysfunction would be important for guiding anti-PD-1 and anti-PD-L1 immunotherapy. Therefore, the updated meta-analysis was conducted to evaluate the incidence risk of thyroid dysfunction caused by PD-1/PD-L1 inhibitors.

Methods: PD-1/PD-L1 inhibitor related clinical trials were collected by a systematic search of the PubMed. Some relevant studies were identified by a manual search. The incidence risk of all grades and grades 3-5 was analyzed and evaluated by random effect model. The Newcastle Ottawa Scale was used for the quality assessment of all clinical trials.

Results: Forty-three clinical trials were collected. Compared with chemotherapy, the risk of hypothyroidism of all grades was significantly higher (OR=7.15, 95%CI:[4.85, 10.55], I = 40%, Z=9.91(0.00001)) in PD-1/PD-L1 group. Similar results could also be noted, when the control group was placebo or CTLA-4. When PD-1/PD-L1 was combined with other treatments for cancer patients, the risk of hypothyroidism of all grades was also significantly increased. Similar to the analysis results of hypothyroidism, PD-1/PD-L1 inhibitors played the same role in increasing the risk of hyperthyroidism and thyroiditis. Few significant analysis results was noted, when the risk of thyroid dysfunction of grades 3-5 was assessed.

Conclusion: Whether used alone or in combination with other anti-tumor drugs, PD-1/PD-L1 inhibitors increased the risk of thyroid dysfunction, especially for hypothyroidism. Furthermore, PD-1/PD-L1 was better than chemotherapy and CTLA-4 in increasing the risk of thyroid dysfunction.
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http://dx.doi.org/10.3389/fonc.2021.667650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312489PMC
July 2021

ILT4 in Colorectal Cancer Cells Induces Suppressive T Cell Contexture and Disease Progression.

Onco Targets Ther 2021 20;14:4239-4254. Epub 2021 Jul 20.

Department of Pathology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250013, People's Republic of China.

Purpose: Immune checkpoint blockade (ICB) therapy shows little or no clinical benefit in most colorectal cancer (CRC) patients, due to the immunosuppressive T cell contexture in the tumor microenvironment (TME). Immunoglobulin-like transcript (ILT) 4 is an immunosuppressive molecule in myeloid cells. ILT4 is enriched in solid tumor cells, facilitating their proliferation, invasion, and metastasis. However, the regulatory role of ILT4 in T cell immunity of CRC is still undetermined. Here, we aimed to explore how tumor cell-derived ILT4 orchestrates T cell infiltration, subset distribution, and function in CRC.

Methods: A total of 145 paraffin-embedded cancer tissues and the corresponding clinicopathological information were collected from CRC patients. Immunohistochemical (IHC) staining and public database analyses determined the correlation of ILT4 expression with different T cell subset densities, IFN-γ levels, and patient outcomes. Paired Ig-like receptor B (PIR-B, ILT4 mouse ortholog)-overexpressing/-downregulated MC38 cells were subcutaneously injected into C57BL/6 mice as a CRC transplantation model. The frequencies, subsets, and IFN-γ levels of T cells in mouse blood and spleens were determined using flow cytometry and immunohistochemistry, respectively.

Results: High ILT4 expression in CRC cells was associated with decreased T cell infiltration, disease progression, and poor patient survival. T cell subset analyses indicated that ILT4-high patients showed reduced CD8 T cell but elevated FOXP3 regulatory T (Treg) cell frequencies in the TME. High ILT4 levels predicted lower IFN-γ production by tumor-infiltrating lymphocytes (TILs), especially by CD8T cells in human CRC tissues. Moreover, PIR-B overexpression accelerated MC38 growth in mice, decreased CD3/CD8/IFN-γ T cell densities, and elevated Treg infiltration in the TME, blood, and spleens. PIR-B knockdown had the opposite effects.

Conclusion: ILT4 in CRC cells induced immunosuppressive T cell subset infiltration and impaired IFN-γ production in TILs, suggesting that ILT4 might be a potential immunotherapeutic target and prognostic biomarker.
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http://dx.doi.org/10.2147/OTT.S290348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312509PMC
July 2021

The Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) burden of care study: Analysis of local treatments for lung metastases and systemic chemotherapy in 220 patients in the PulMiCC cohort.

Colorectal Dis 2021 Jul 26. Epub 2021 Jul 26.

Sussex Health Outcomes Research and Education in Cancer (SHORE-C), University of Sussex, Falmer, UK.

Aim: The aim of this work was to examine the burden of further treatments in patients with colorectal cancer following a decision about lung metastasectomy.

Method: Five teams participating in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study provided details on subsequent local treatments for lung metastases, including the use of chemotherapy. For patients in three groups (no metastasectomy, one metastasectomy or multiple local interventions), baseline factors and selection criteria for additional treatments were examined.

Results: The five teams recruited 220 patients between October 2010 and January 2017. No lung metastasectomy was performed in 51 patients, 114 patients had one metastasectomy and 55 patients had multiple local interventions. Selection for initial metastasectomy was associated with nonelevated carcinoembryonic antigen, fewer metastases and no prior liver metastasectomy. These patients also had better Eastern Cooperative Oncology Group scores and lung function at baseline. Four sites provided information on chemotherapy in 139 patients: 79 (57%) had one to five courses of chemotherapy, to a total of 179 courses. The patterns of survival after one or multiple metastasectomy interventions showed evidence of guarantee-time bias contributing to an impression of benefit over no metastasectomy. After repeated metastasectomy, a significantly higher risk of death was observed, with no apparent reduction in chemotherapy usage.

Conclusion: Repeated metastasectomy is associated with a higher risk of death without reducing the use of chemotherapy. Continued monitoring without surgery might reassure patients with indolent disease or allow response assessment during systemic treatment. Overall, the carefully collected information from the PulMICC study provides no indication of an important survival benefit from metastasectomy.
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http://dx.doi.org/10.1111/codi.15833DOI Listing
July 2021

Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma.

Br J Haematol 2021 Jul 22. Epub 2021 Jul 22.

University Medical Center Groningen, Groningen, Netherlands, on behalf of HOVON/PPLC.

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10  CAR-T cells/kg (day 0) and once-daily oral dexamethasone [10 mg, day 0 (before axi-cel) through day 2]. Forty patients received axi-cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty-eight per cent of patients did not experience CRS or NEs within 72 h of axi-cel. With a median follow-up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.
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http://dx.doi.org/10.1111/bjh.17527DOI Listing
July 2021

METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis.

Front Med (Lausanne) 2021 6;8:607585. Epub 2021 Jul 6.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China.

Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the -methyladenosine (mA) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response the NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fmed.2021.607585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290917PMC
July 2021

Paper-based wearable electronics.

iScience 2021 Jul 17;24(7):102736. Epub 2021 Jun 17.

Department of Biomedical, Biological & Chemical Engineering, University of Missouri, Columbia, MO 65211, USA.

Skin-interfaced wearable electronics can find a broad spectrum of applications in healthcare, human-machine interface, robotics, and others. The state-of-the-art wearable electronics usually suffer from costly and complex fabrication procedures and nonbiodegradable polymer substrates. Paper, comprising entangled micro- or nano-scale cellulose fibers, is compatible with scalable fabrication techniques and emerges as a sustainable, inexpensive, disposable, and biocompatible substrate for wearable electronics. Given various attractive properties (e.g., breathability, flexibility, biocompatibility, and biodegradability) and rich tunability of surface chemistry and porous structures, paper offers many exciting opportunities for wearable electronics. In this review, we first introduce the intriguing properties of paper-based wearable electronics and strategies for cellulose modifications to satisfy specific demands. We then overview the applications of paper-based devices in biosensing, energy storage and generation, optoelectronics, soft actuators, and several others. Finally, we discuss some challenges that need to be addressed before practical uses and wide implementation of paper-based wearable electronics.
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http://dx.doi.org/10.1016/j.isci.2021.102736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261674PMC
July 2021

Tunable polarization-sensitive, long-wave infrared MDM subwavelength grating structure with wide-angle, narrow-band, and high absorption.

Opt Express 2021 Jul;29(14):21473-21491

This paper proposes a polarization-sensitive, metal-dielectric-metal (MDM) subwavelength grating structure based on surface plasmon resonance that achieves wide-angle, narrow-band, and high absorption in the long-infrared region. The resonance characteristics of the MDM structure, excited by magnetic resonance (MR), cause the transverse magnetic (TM) and transverse electric (TE) modes to polarize. A model of the inductor capacitor (LC) circuit is also presented. Structural simulations demonstrate a near-perfect absorption characteristic (99.99%) at 9 µm center wavelength. For TM polarization with incident angles ranging from 0° to 89°, the MDM grating structure produced absorption rates over 90%, 81%, and 71% for incident angles of 66°, 73°, and 77°, respectively. The absorption peaks in the long-wave infrared band can be adjusted by varying the duty cycle or period, without adjusting structural parameters. The spectral absorption curve shows a red shift and maintains high absorption, with wide-angle and narrow-band, across various azimuth angles (0-90°), during an increase in duty cycle or period. This method reduces the difficulty and complexity of micro-nano processing, and enables multiple absorbers in the long-infrared band (7.5-13 µm) to be processed and prepared on the same substrate surface.
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http://dx.doi.org/10.1364/OE.428427DOI Listing
July 2021

A Scoping Review of Cross-Sectional Studies on Traditional Chinese Medicine.

Am J Chin Med 2021 14;49(6):1275-1296. Epub 2021 Jul 14.

Hong Kong Chinese Medicine Clinical Study Center, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China.

Cross-sectional studies on traditional Chinese medicine (TCM-CSs) have become the most published type of TCM observational study; however, the research scope of current TCM-CSs is unknown. A scoping review of the literature was performed. A descriptive approach to summarize the core study characteristics was prepared, along with structured tables and figures to identify salient points of similarities and differences noted across studies. The reporting quality of TCM-CSs was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) cross-sectional checklist. Eight databases (Embase, CENTRAL, MEDLINE, AMED, CBM, CNKI, WanFang, and VIP) were systematically searched for TCM-CSs published up until 20 January 2020. The literature screening and evaluating were independently conducted by two researchers. When there was disagreement, a third-party senior researcher made the judgment. A total of 198 TCM-CSs published between 1997 and 2019 were included, 160 English studies and 38 Chinese studies, respectively. More TCM-CSs were published in each successive year. The journal published more TCM-CSs (24) than any other journal. Most TCM-CSs were conducted in mainland China (81, 40.9%), followed by Taiwan, China (44, 22.2%) and HKSAR, China (19, 9.6%). The most commonly used sampling method was purposive sampling (94, 47.5%), following by convenience sampling (60, 30.3%). The research topics can be summarized in four major categories as follows: constitution-related research (11.1%), TCM pattern-related research (18.7%), TCM intervention-related research (55.1%), and others (15.6%). The average sufficient reporting rate of included TCM-CSs according to the STROBE cross-sectional checklist was 45.6%. Papers written in English reported 9 items (items 2, 4, 14a, 16a, 18, 19, 20, 21, and 22) more frequently than papers written in Chinese. The number of TCM-CSs is increasing. Research topics are diverse; however, the reporting quality is unsatisfactory. In particular, TCM-CSs need greater transparency and standardization.
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http://dx.doi.org/10.1142/S0192415X21500610DOI Listing
July 2021

Influential factors and prediction model of mammographic density among Chinese women.

Medicine (Baltimore) 2021 Jul;100(28):e26586

Department of Neurosurgery, Liaoning Cancer Hospital& Institute (Cancer Hospital of China Medical University), Shenyang, China.

Abstract: To evaluate the characteristics and influential factors of breast density and establish a new model for predicting breast density in Chinese women, so as to provide a basis for breast cancer screening techniques and duration.A total of 9412 women who were selected from screening and intervention techniques for Breast and Cervical Cancer Project between April 2018 and June 2019 were enrolled in this study. Selected women were randomly assigned to training and validation sets in a ratio of 1:1. Univariable and multivariable analyzes were performed by Logistic regression model. Nomogram was generated according to the results of multivariate analysis. Calibration, area under curve (AUC) and akaike information criterion (AIC) were used for measuring accuracy of prediction model.There were 377 (4.0%) women in breast imaging reporting and data system (BI-RADS) A category, 2164 (23.0%) in B category, 5749 (61.1%) in C category and 1122 (11.9%) in D category. Age duration, educational attainment, history of benign diseases, breastfeeding history, menopausal status, and body mass index (BMI) were imputed as independent influential factors for breast density in multivariable analysis. The AUC and AIC of training and validation set were 0.7158, 0.7139, and 4915.378, 4998.665, respectively.This study indicated that age, educational attainment, history of benign breast disease, breastfeeding history, menopausal status and BMI were independent influential factors of breast density. Nomogram generated on the basis of these factors could relatively predict breast density, which in turn could be used for recommendations of breast cancer screening techniques.
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http://dx.doi.org/10.1097/MD.0000000000026586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284716PMC
July 2021

Effects of miR-202-5p silencing PIK3CA gene expression on proliferation, invasion, and epithelial-mesenchymal transition of cervical cancer SiHa cells through inhibiting PI3K/Akt/mTOR signaling pathway activation.

Mol Cell Biochem 2021 Jul 9. Epub 2021 Jul 9.

Department of Gynecology and Obstetrics, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang City, 050031, Hebei Province, People's Republic of China.

To explore the mechanism of miR-202-5p targeting the expression of PIK3CA and mediating the activation of PI3K/Akt/mTOR signaling pathway on the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer. The objects of study were 105 cases of cervical cancer and their corresponding normal tissues. qRT-PCR was used to detect the expression of miR-202-5p and PIK3CA in adjacent normal tissue and cervical cancer tissue. Dual luciferase reporter assay was used to verify the targeting relationship between miR-202-5p and PIK3CA gene. Human cervical cancer cell lines HPV-16E6, SiHa, HeLa, and CaSki were purchased for our cell experiments. The expression levels of PIK3CA in the cells were detected by qRT-PCR. The cell line with higher expression levels was selected to complete the follow-up experiment. The cultured cells were transfected and divided into the miR-202-5p mimic NC group, miR-202-5p mimic group, miR-202-5p inhibitor NC group, miR-202-5p inhibitor group, siRNA-PIK3CA NC group, siRNA-PIK3CA group, miR-202-5p inhibitor NC + siRNA-PIK3CA NC group, miR-202-5p inhibitor + siRNA-PIK3CA NC group, and miR-202-5p inhibitor + siRNA-PIK3CA group. QRT-PCR was used to detect the expression of miR-202-5p. Western blot and qRT-PCR were applied to detect the mRNA and protein expression levels of related pathway proteins (PIK3CA, PI3K, PTEN, p-Akt1, and p-mTOR) and epithelial-mesenchymal transition-related factors (N-cadherin, E-cadherin, and vimentin). Cell proliferation was detected by plate colony formation assay. Transwell assay was used to detect the invasion ability of each group. When compared with the adjacent tissues, PIK3CA mRNA expression level was significantly increased and miR-202-5p expression level was significantly decreased in cervical cancer tissues (all P < 0.05). PIK3CA was a target gene of miR-202-5p. The mRNA expression level of PIK3CA in SiHa cervical cancer cells was significantly higher than that in CaSki, HeLa, and HPV-16E6 cells (all P < 0.05), and SiHa cervical cancer cells were selected to complete the follow-up experiments. When compared with the corresponding NC group, the expression of miR-202-5p in miR-202-5p mimic group was increased. In addition, the mRNA and protein expression levels of E-cadherin and PTEN in miR-202-5p mimic and siRNA-PIK3CA groups were increased, and the protein expression of p-Akt1 and p-mTOR was decreased, and also, the mRNA and protein expression levels of PIK3CA, PI3K, N-cadherin, and vimentin were decreased (all P < 0.05); in miR-202-5p inhibitor group, the expression levels of miR-202-5p, E-cadherin, and PTEN decreased, the protein expression of p-Akt1 and p-mTOR increased, and the mRNA and protein expression of PIK3CA, PI3K, N-cadherin, and vimentin increased in miR-202-5p inhibitor group (all P < 0.05); in miR-202-5p inhibitor + siRNA-PIK3CA group, the expression of miR-202-5p decreased (P < 0.05), but the mRNA and protein expression of PIK3CA, PI3K, p-Akt1, p-mTOR, N-cadherin, E-cadherin, and vimentin had no significant changes (all P > 0.05). When compared with the corresponding NC group, the number of cell clones in miR-202-5p mimic group and siRNA-PIK3CA group was decreased, and the invasion ability of miR-202-5p inhibitor group was increased, and the invasion ability was enhanced (all P < 0.05); miR-202-5p inhibitor + siRNA-PIK3CA group showed no significant change in the number of cell clones and the rate of invasion (P > 0.05). In conclusion, the overexpression of miR-202-5p can suppress PIK3CA gene expression and the activation of PI3K/Akt/mTOR signaling pathway to suppress the proliferation, invasion, and EMT of cervical cancer.
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http://dx.doi.org/10.1007/s11010-021-04211-4DOI Listing
July 2021

Ultrastable Tb-Organic Framework as a Selective Sensor of Phenylglyoxylic Acid in Urine.

ACS Appl Mater Interfaces 2021 Jul 8;13(28):33546-33556. Epub 2021 Jul 8.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.

Industrial pollution and harmful chemicals seriously affect environment and human health. Styrene is a common air toxicant with widespread exposure sources, including smoking, automobile exhaust, and plastic pollutants. Phenylglyoxylic acid (PGA) is a typical biomarker for exposed styrene. Therefore, it is crucial to quickly identify and quantitatively detect PGA. Herein, an ultrastable terbium metal-organic framework (Tb-MOF ) was developed, and the luminescence film (/PLA) consisting of polylactic acid (PLA) and was fabricated as a sensor for rapid detection of PGA. The sensor possesses the advantages of efficient detection [limit of detection (LOD) is 1.05 × 10 mg/mL] and rapid response speed (less than 10 s) for PGA in urine. Furthermore, this sensor exhibits high stability, outstanding anti-interference ability, and excellent recyclability. Based on this film technology, a paper-based probe was then developed for portable and convenient detection. The probe could easily distinguish different concentrations of PGA under the naked eye toward practical sensing applications. Meanwhile, photoinduced electron transfer was demonstrated to be responsible for the luminescence sensing. Hence, this study indicates that Tb-MOF is a promising material to detect PGA for evaluating the effect of styrene on the body.
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http://dx.doi.org/10.1021/acsami.1c09202DOI Listing
July 2021

Lp-PLA2 inhibition prevents Ang II-induced cardiac inflammation and fibrosis by blocking macrophage NLRP3 inflammasome activation.

Acta Pharmacol Sin 2021 Jul 5. Epub 2021 Jul 5.

State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling, whereas effective pharmacological treatments targeting cardiac inflammation remain unclear. Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to vascular inflammation-related diseases by mediating macrophage migration and activation. Darapladib, the most advanced Lp-PLA2 inhibitor, has been evaluated in phase III trials in atherosclerosis patients. However, the role of darapladib in inhibiting hypertensive cardiac fibrosis remains unknown. Using a murine angiotensin II (Ang II) infusion-induced hypertension model, we found that Pla2g7 (the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue, and it was primarily localized in heart-infiltrating macrophages. As expected, darapladib significantly prevented Ang II-induced cardiac fibrosis, ventricular hypertrophy, and cardiac dysfunction, with potent abatement of macrophage infiltration and inflammatory response. RNA sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation, extracellular matrix, and proliferation. Moreover, darapladib substantially reduced the Ang II infusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1β and markedly attenuated caspase-1 activation in cardiac tissues. Furthermore, darapladib ameliorated Ang II-stimulated macrophage migration and IL-1β secretion in macrophages by blocking NLRP3 inflammasome activation. Darapladib also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in macrophages. Overall, our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition, elucidating the protective effects of suppressing NLRP3 inflammasome activation. Lp-PLA2 inhibition by darapladib represents a novel therapeutic strategy for hypertensive cardiac damage treatment.
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http://dx.doi.org/10.1038/s41401-021-00703-7DOI Listing
July 2021

A systematic study on the chemical diversity and efficacy of the inflorescence and succulent stem of .

Food Funct 2021 Jul 5. Epub 2021 Jul 5.

Key Laboratory of Chinese Medicine Resources Conservation, State Administration of Traditional Chinese Medicine of the People's Republic of China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Cynomorium songaricum is a medicinal, edible, and endangered plant species. Since inflorescences are not considered medicinal parts, their discard causes a waste of resources. To expand the medicinal uses of C. songaricum, we evaluated their chemistry and pharmacology by applying widely targeted metabolomics, network pharmacology, and molecular docking. Widely targeted metabolomics results indicated chemical diversity in C. songaricum with 599 compounds. Among them, 280 compounds were different between the succulent stem and inflorescence. With 218 upregulated compounds, inflorescence has more abundant compounds than the succulent stem, especially pigment compounds such as flavonols, flavones, and flavanones. Moreover, anthocyanin and proanthocyanidin were unique compounds in the inflorescence and succulent stem, respectively. Sixty-five compounds in inflorescence and 18 compounds in succulent stems were found to be associated with atherosclerosis in the network pharmacology analysis. Tests revealed that inflorescence had a stronger anti-atherosclerotic effect than succulent stems. Molecular docking analysis revealed that 30 compounds (29 pigment compounds) in inflorescence and 6 compounds (4 pigment compounds) in succulent stem showed strong binding affinities with three target proteins, namely ALB, MPO, and NOS2, especially amentoflavone, quercetin 7-O-rutinoside, and luteolin 7-O-glucoside (cynaroside). Results demonstrated that the inflorescence is rich in pigment compounds and has a potential anti-atherosclerosis effect. This study provides novel methods and ideas for the sustainable development of endangered medicinal plants.
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http://dx.doi.org/10.1039/d1fo01275dDOI Listing
July 2021

The molecular biology of pancreatic adenocarcinoma: translational challenges and clinical perspectives.

Signal Transduct Target Ther 2021 Jul 5;6(1):249. Epub 2021 Jul 5.

Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, Shanghai, China.

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.
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http://dx.doi.org/10.1038/s41392-021-00659-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255319PMC
July 2021

Loss of Function of Resulted in Pepper-Shaped Husk in Rice.

Life (Basel) 2021 Jun 3;11(6). Epub 2021 Jun 3.

Institute of Biotechnology, Fujian Academy of Agricultural Sciences, Fuzhou 350003, China.

Grain shape is one of the most important and complex traits determining the grain yield in rice. In this study, we discovered two rice mutants with defective shape spikelets, designated as (pepper-shaped husk 1-1/2), which were both isolated from the tissue-culture-regenerated plants of cultivar Minghui 86. The two mutants showed the same mutant phenotypes, containing pepper-shaped spikelets; shorter, smaller and compact panicles; very low seed-setting rate; high percentage of split grains; and lower grain width. Genetic analysis indicated that the mutant phenotypes were controlled by a recessive gene. Gene mapping indicated that the target gene was located on the short arm of chromosome 4. Sequencing analysis revealed that the two mutants each had a different nonsense mutation in , confirming that the target gene is . Compared with the previously reported mutant , possessed some distinct mutant phenotypes, probably because of the influence of different genetic background, suggesting that may function differently under different genetic backgrounds.
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http://dx.doi.org/10.3390/life11060523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227114PMC
June 2021

Genetically predicted body composition in relation to cardiometabolic traits: a Mendelian randomization study.

Eur J Epidemiol 2021 Jun 30. Epub 2021 Jun 30.

Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan Institute for Metabolic Diseases, and Human Phenome Institute, Fudan University, NO.180 Fenglin Road, Shanghai, 200032, China.

Fat mass and fat-free mass are found to be associated with different health outcomes in observational studies, but the underlying causality remains unclear. We aimed to investigate the causal relationships between body composition and cardiometabolic traits using a two-sample Mendelian randomization (MR) approach. Independent genetic variants associated with body fat mass, fat-free mass, and fat percentage in UK Biobank population were used as genetic instrumental variables, and their causal effects on circulatory diseases, type 2 diabetes, glycemic traits, and lipid fractions were estimated from large-scale genome-wide association studies (GWAS) in European populations. Univariable, multivariable, and bidirectional MR analyses were performed. Genetically predicted high fat mass and fat percentage significantly increased risks of most cardiometabolic diseases, and high fat-free mass had protective effects on most cardiometabolic diseases after accounting for fat mass. Fat mass, fat-free mass, and fat percentage were all positively associated with higher risks of atrial fibrillation and flutter, varicose veins, and deep vein thrombosis and pulmonary embolism. High fat mass increased fasting glucose, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, decreased high-density lipoprotein cholesterol, and high fat-free mass reduced HOMA-IR, triglycerides, and low-density lipoprotein cholesterol. Genetically predicted fat-free mass was bidirectionally negatively associated with 2-h glucose and total cholesterol. The findings may be helpful in risk stratification and tailoring management of body composition in patients with different cardiometabolic statuses.
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http://dx.doi.org/10.1007/s10654-021-00779-9DOI Listing
June 2021

Spectroscopic and docking studies of the interaction mechanisms of xylitol with α-casein and κ-casein.

Colloids Surf B Biointerfaces 2021 Jun 17;206:111930. Epub 2021 Jun 17.

College of Food Science, Shenyang Agriculture University, Shenyang, 110866, China. Electronic address:

The molecular interactions of xylitol (XY) with α-casein (α-CN) and κ-casein (κ-CN) at pH 7.4 as a function of temperature (298, 308, and 318 K) were characterized by multispectral techniques and molecular docking. The fluorescence results showed that XY strongly quenched the intrinsic fluorescence of α- and κ-CN by static quenching, as well as the presence of a single binding site for XY on both proteins with a binding constant value of ∼10 L/mol. The binding affinity of both proteins for XY decreased with increasing temperature, and Van der Waals forces, hydrogen bonding and protonation were the key forces in the interactions. The addition of XY altered the polarity of the microenvironment of proteins and changed their secondary structure from ordered to disordered. The molecular docking results showed that XY had different binding sites to α- and κ-CN, with several amino acids involved in the binding processes.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111930DOI Listing
June 2021

Nicotine Causes Mitochondrial Dynamics Imbalance and Apoptosis Through ROS Mediated Mitophagy Impairment in Cardiomyocytes.

Front Physiol 2021 10;12:650055. Epub 2021 Jun 10.

Research Center of Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Nicotine contained in traditional cigarettes, hookahs, and e-cigarettes is an important risk factor for cardiovascular disease. Our previous study showed that macroautophagic flux impairment occurred under nicotine stimulation. However, whether nicotine influences mitochondrial dynamics in neonatal rat ventricular myocytes (NRVMs) is unclear. The purpose of this study was to explore the effects and potential mechanism of nicotine on mitophagy, mitochondrial dynamics, apoptosis, and the relationship between these processes in NRVMs. Our results showed that nicotine exposure increased mitochondria-derived superoxide production, decreased mitochondrial membrane potential, and impaired PINK1/Parkin-mediated mitophagic flux in NRVMs. Interestingly, nicotine significantly promoted dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and suppressed mitofusin (MFN)-mediated fusion, which was also observed in the bafilomycin A1-treated group. These results suggest that mitophagic flux impairment may contribute to Drp-1-mediated mitochondrial fission. Finally, nicotine caused excessive mitochondrial fission and contributed to apoptosis, which could be alleviated by mdivi-1, an inhibitor of Drp1. In addition to CTSB, as we previously reported, the enzyme activity of cathepsin L (CTSL) was also decreased in lysosomes after stimulation with nicotine, which may be the main cause of the hindered mitophagic flux induced by nicotine in NRVMs. Pretreatment with Torin 1, which is an inhibitor of mTOR, activated CTSL and ameliorated nicotine-induced mTOR activation and mitophagy impairment, decreased mitochondria-derived superoxide production, and blunted mitochondrial fission and apoptosis. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) or inhibitors of p38 and JNK, which could also alleviate mitophagy impairment, exhibited similar effects as Torin1 on mitochondria. Taken together, our study demonstrated that nicotine treatment may lead to an increase in Drp1-mediated mitochondrial fission by blocking mitophagic flux by weakening the enzyme activity of CTSL and activating the ROS/p38/JNK signaling pathway. Excessive mitochondrial fission induced by nicotine ultimately leads to apoptosis. Torin1 restored the decreased CTSL enzyme activity by removing excessive ROS and alleviated the effects of nicotine on mitophagic flux, mitochondrial dynamics, and apoptosis. These results may provide new evidence on the relationship between mitophagic flux and mitochondrial dynamics and new perspectives on nicotine's effects on mitochondrial dynamics in cardiomyocytes.
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http://dx.doi.org/10.3389/fphys.2021.650055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222989PMC
June 2021

Corrigendum to: The glutamate receptors AtGLR1.2 and AtGLR1.3 increase cold tolerance by regulating jasmonate signaling in Arabidopsis thaliana.

Biochem Biophys Res Commun 2021 Aug 25;566:211-213. Epub 2021 Jun 25.

Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbrc.2021.06.061DOI Listing
August 2021

Divergence of the genetic contribution of FRIGIDA homologues in regulating the flowering time in Brassica rapa ssp. rapa.

Gene 2021 Sep 25;796-797:145790. Epub 2021 Jun 25.

Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; Plant Germplasm and Genomics Center, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China. Electronic address:

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http://dx.doi.org/10.1016/j.gene.2021.145790DOI Listing
September 2021

Accommodating Strategic Players in Distributed Algorithms for Power Dispatch Problems.

IEEE Trans Cybern 2021 Jun 24;PP. Epub 2021 Jun 24.

Distributed algorithms are gaining increasing research interests in the area of power system optimization and dispatch. Existing distributed power dispatch algorithms (DPDAs) usually assume that suppliers/consumers bid truthfully. However, this article shows the need for DPDAs to consider strategic players and to take account of their behavior deviation from what the DPDAs expect. To address this, we propose a distributed strategy update algorithm (DSUA) on top of a DPDA. The DSUA considers strategic suppliers who optimize their bids in a DPDA, using only the information accessible from a DPDA, that is, price. The DSUA also considers the cases when suppliers update bids alternately or simultaneously. Under both cases, we show the closeness of supplier bids to the Nash equilibrium via game-theoretic analysis as well as simulation.
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http://dx.doi.org/10.1109/TCYB.2021.3085400DOI Listing
June 2021

mixture attenuates renal damage in rats with diabetic nephropathy by inhibiting the PI3K/Akt/mTOR pathway.

Mol Med Rep 2021 Aug 24;24(2). Epub 2021 Jun 24.

School of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

mixture (DMix) is a Traditional Chinese Medicine widely used for preventing and treating diabetic nephropathy (DN). Autophagy contributes to DN development and progression. The present study aimed to investigate the mechanism underlying the protective effects of DMix on the kidneys of rats with DN and to determine whether this involves autophagy. Herein, a high‑sugar and high‑fat diet, combined with the intra‑abdominal injection of low‑dose streptozocin, was used to induce DN in 40 Sprague‑Dawley male rats. In total, 10 additional rats were used as controls. The rats with DN were then randomly divided into three groups and treated with DMix, gliquidone or saline via gastric administration for 8 weeks. Body weight, kidney weight, kidney index, fasting blood glucose (FBG), blood lipid, hemoglobin A1c (HbA1c), insulin, blood urea nitrogen and serum creatinine levels, as well as the 24‑h urinary albumin excretion rate (UAER) were measured. H&E, Periodic Acid‑Schiff and Masson staining were used to examine the renal pathology. The mRNA and protein expression levels of LC3 and Beclin‑1 in renal tissues were measured using reverse transcription‑quantitative PCR and immunohistochemistry, respectively. Western blotting was conducted to measure the protein expression levels of PI3K, phosphorylated (p)‑PI3K, Akt, p‑Akt, mTOR, p‑mTOR, LC3 and Beclin‑1 in renal tissues. It was found that DMix significantly reduced the FBG, blood lipids, HbA1c and insulin levels, kidney weight, kidney index and UAER in rats with DN, as well as improved renal function. Rats with DN showed notable glomerular hypertrophy, an increase in mesangial matrix content and renal interstitial fibrosis. Moreover, DMix notably reduced kidney damage. The results demonstrated that DMix inhibited the phosphorylation of PI3K, Akt and mTOR in the kidney tissues of rats with DN, and increased the protein and mRNA expression levels of LC3 and Beclin‑1. Therefore, it was suggested that DMix has protective effects on the kidney of rats with DN, which may be associated with the inhibition of the PI3K/Akt/mTOR signaling pathway and activation of renal autophagy by this traditional medicine.
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http://dx.doi.org/10.3892/mmr.2021.12229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222963PMC
August 2021

Amplitude Mode in Quantum Magnets via Dimensional Crossover.

Phys Rev Lett 2021 Jun;126(22):227201

Department of Physics and HKU-UCAS Joint Institute of Theoretical and Computational Physics, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.

We investigate the amplitude (Higgs) mode associated with longitudinal fluctuations of the order parameter at the continuous spontaneous symmetry breaking phase transition. In quantum magnets, due to the fast decay of the amplitude mode into low-energy Goldstone excitations, direct observation of this mode represents a challenging task. By focusing on a quasi-one-dimensional geometry, we circumvent the difficulty and investigate the amplitude mode in a system of weakly coupled spin chains with the help of quantum Monte Carlo simulations, stochastic analytic continuation, and a chain-mean field approach combined with a mapping to the field-theoretic sine-Gordon model. The amplitude mode is observed to emerge in the longitudinal spin susceptibility in the presence of a weak symmetry-breaking staggered field. A conventional measure of the amplitude mode in higher dimensions, the singlet bond mode, is found to appear at a lower than the amplitude mode frequency. We identify these two excitations with the second (first) breather of the sine-Gordon theory, correspondingly. In contrast to higher-dimensional systems, the amplitude and bond order fluctuations are found to carry significant spectral weight in the quasi-1D limit.
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http://dx.doi.org/10.1103/PhysRevLett.126.227201DOI Listing
June 2021

Reversible GABAergic dysfunction involved in hippocampal hyperactivity predicts early-stage Alzheimer disease in a mouse model.

Alzheimers Res Ther 2021 06 14;13(1):114. Epub 2021 Jun 14.

Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing, 100069, China.

Background: Neuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown.

Methods: Here, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Biochemical methods, electron microscopic imaging, behavioral tests, and intraventricular drug delivery applied with osmotic pumps were used in this study.

Results: We confirmed hyperactivity of hippocampal CA1 pyramidal neurons in 5XFAD mice using whole-cell electrophysiological recording at 2.5 months old, when local Aβ-positive plaques had not developed and only mild cognitive dysfunction occurred. We further discovered attenuated inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents in CA1 pyramidal neurons, in which the intrinsic excitability was unchanged. Moreover, the density of both γ-aminobutyric acid A (GABA) receptor subunits, α1 and γ2, was reduced in synapses of the hippocampus in transgenic mice. Intriguingly, early intervention with the GABA receptor agonist gaboxadol reversed the hippocampal hyperactivity and modestly ameliorated cognitive performance in 5XFAD mice under our experimental conditions.

Conclusions: Inhibitory postsynaptic disruption critically contributes to abnormalities in the hippocampal network and cognition in 5XFAD mice and possibly in AD. Therefore, strengthening the GABAergic system could be a promising therapy for AD in the early stages.
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http://dx.doi.org/10.1186/s13195-021-00859-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204558PMC
June 2021

Construction of C-C bonds via photoreductive coupling of ketones and aldehydes in the metal-organic-framework MFM-300(Cr).

Nat Commun 2021 Jun 11;12(1):3583. Epub 2021 Jun 11.

Department of Chemistry, University of Manchester, Manchester, UK.

Construction of C-C bonds via reductive coupling of aldehydes and ketones is hindered by the highly negative reduction potential of these carbonyl substrates, particularly ketones, and this renders the formation of ketyl radicals extremely endergonic. Here, we report the efficient activation of carbonyl compounds by the formation of specific host-guest interactions in a hydroxyl-decorated porous photocatalyst. MFM-300(Cr) exhibits a band gap of 1.75 eV and shows excellent catalytic activity and stability towards the photoreductive coupling of 30 different aldehydes and ketones to the corresponding 1,2-diols at room temperature. Synchrotron X-ray diffraction and electron paramagnetic resonance spectroscopy confirm the generation of ketyl radicals via confinement within MFM-300(Cr). This protocol removes simultaneously the need for a precious metal-based photocatalyst or for amine-based sacrificial agents for the photochemical synthesis.
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http://dx.doi.org/10.1038/s41467-021-23302-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196067PMC
June 2021

Consuming Different Structural Parts of Bamboo Induce Gut Microbiome Changes in Captive Giant Pandas.

Curr Microbiol 2021 Aug 9;78(8):2998-3009. Epub 2021 Jun 9.

Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China.

Giant pandas consume different structural parts of bamboo (shoots, leaves and culms) during different seasons. Previous research showed different bamboo parts have varying nutritional content and that a long-term diet consisting of a single part of bamboo resulted in remarkable metabolic changes within captive giant pandas. However, the effects on the gut microbiome of giant pandas, as a result of a single bamboo part diet, have not been investigated. Here, we evaluated the changes in gut microbial communities based on single bamboo part diets and their potential implications by using 16S rRNA gene-based amplicon sequencing and metagenome shotgun sequencing. We found that the composition and function of the gut microbiome from captive giant pandas fed exclusively culms were significantly different from that of individuals fed shoots or leaves. During the culm feeding period, the gut microbiome showed strongest digestive capabilities for cellulose, hemicellulose and starch, and had the highest potential abilities for the biosynthesis of bile acids, fatty acids and amino acids. This suggests the microbiome aids in breaking down culm, which is more difficult for giant pandas to digest, as a means to compensate for the nutrient poor content of the culm. Genes related to fatty acid metabolism and tricarboxylic acid cycle enzymes were more abundant during the leaf stage diet than that in the shoot and culm stages. Thus, the microbiome may help giant pandas, which typically have low lipase levels, with fat digestion. These results illustrate that adaptive changes in the gut microbiome community and function may be an important mechanism to aid giant panda digestion when consuming different structural parts of bamboo.
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http://dx.doi.org/10.1007/s00284-021-02503-yDOI Listing
August 2021

XENOBIOTIC CONSTITUTIVE ANDROSTANE RECEPTOR (CAR) IS HIGHLY INDUCED IN PSORIASIS AND PROMOTES KERATINOCYTE PROLIFERATION.

J Invest Dermatol 2021 Jun 4. Epub 2021 Jun 4.

The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China.

Psoriasis is a chronic inflammatory skin disease with abnormal epidermal proliferation. Xenobiotics contribute to the pathogenesis of psoriasis. The mechanism linking xenobiotic stimuli with epidermal proliferation remains largely unknown. Here, we investigated a role of constitutive androstane receptor (CAR), a nuclear receptor (NR1I3) responsible for xenobiotics detoxification. We showed that CAR and its target genes were induced in the lesions from psoriasis patients and imiquimod (IMQ)-treated mice. Pro-inflammatory cytokines (IL-17A, IL-22, Oncostatin M, IL-1α and TNF-α) synergistically increased the expressions of CAR and its target genes in both human and mouse keratinocytes. Overexpression of CAR promoted whereas silencing of CAR attenuated the G1/S transition by regulating cyclin E and c-Myc expressions. Importantly, a selective CAR agonist CITCO or the pro-inflammatory cytokines induced cyclin E and c-Myc, which were largely blocked by clotrimazole, a selective CAR antagonist, or CAR siRNA. In addition, we showed that topical application of TCPOBOP, a selective agonist for mouse CAR, exacerbated the IMQ-induced psoriasis lesions with increased expressions of proliferative and inflammatory markers. In contrast, CAR knock-out mice developed significantly milder lesions. In conclusion, these results demonstrated that CAR plays a pathogenic role and, potentially, may be a target for the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.jid.2021.05.017DOI Listing
June 2021

LncRNA SAMMSON Mediates Adaptive Resistance to RAF Inhibition in BRAF-Mutant Melanoma Cells.

Cancer Res 2021 Jun 18;81(11):2918-2929. Epub 2021 Mar 18.

Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

The long noncoding RNA (lncRNA) SAMMSON is required for human melanoma cell growth and survival. However, whether SAMMSON regulates the response of mutant BRAF melanoma cells to RAF inhibitors remains unknown. In this work, we showed that SAMMSON is rapidly induced upon inhibition of ERK signaling, and SAMMSON overexpression conferred resistance to vemurafenib-induced cytotoxicity in melanoma cells. SOX10 mediated transcriptional induction of SAMMSON by vemurafenib, and SOX10 sumoylation at K55 was essential for this function. In addition, depletion of SAMMSON activated p53 signaling, which is dependent on the SAMMSON-interacting protein CARF. Depletion of SAMMSON sensitized mutant BRAF melanoma cells to RAF inhibitors and , while CARF knockdown reversed the enhanced sensitivity. In summary, these findings suggest that SAMMSON may function as a new mediator of adaptive resistance to RAF inhibitors in melanoma by modulating CARF-p53 signaling. SIGNIFICANCE: This study highlights the role of a SAMMSON/CARF/p53 signaling axis in modulating the adaptive resistance of mutant BRAF melanoma to RAF inhibitors.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3145DOI Listing
June 2021

Integrated analysis of long non-coding RNAs (lncRNAs) and mRNA expression profiles identifies lncRNA PRKG1-AS1 playing important roles in skeletal muscle aging.

Aging (Albany NY) 2021 05 29;13(11):15044-15060. Epub 2021 May 29.

Department of Geriatrics, The First Hospital of Jilin University, Changchun 130021, Jilin, P.R. China.

This study aimed to identify long non-coding RNAs (lncRNAs) involving in the skeletal muscle aging process. Skeletal muscle samples from old and young subjects were collected for lncRNA-sequencing. Differentially expressed genes (DEGs) and DElncRNAs between young and old groups were identified and a co-expression network was built. Further, a dexamethasone-induced muscle atrophy cell model was established to characterize the function of a critical lncRNA. A total of 424 DEGs, including 271 upregulated genes and 153 downregulated genes as well as 152 DElncRNAs including 76 up-regulated and 76 down-regulated lncRNAs were obtained. Functional analysis demonstrated that the DEGs were significantly related to immune response. Coexpression network demonstrated lncRNA AC004797.1, PRKG1-AS1 and GRPC5D-AS1 were crucial lncRNAs. Their expressions were further validated by qRT-PCR in human skeletal muscle and the muscle atrophy cell model. Further analysis suggested that knock-down of PRKG1-AS1 could significantly increase cell viability and decrease cell apoptosis. qRT-PCR and western blot analyses demonstrated that knock-down of PRKG1-AS1 could increase the expression of MyoD, MyoG and Mef2c. This study demonstrated that lncRNAs of GPRC5D-AS1, AC004797.1 and PRKG1-AS1 might involve the aging-associated disease processes.
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http://dx.doi.org/10.18632/aging.203067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221296PMC
May 2021
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