Publications by authors named "Jingwen Wang"

277 Publications

Enhanced degradation of tetrabromobisphenol A by Fe/sulfite process under simulated sunlight irradiation.

Chemosphere 2021 Jul 6;285:131442. Epub 2021 Jul 6.

School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China; Hubei Provincial Engineering Research Center for Water Quality Safety and Pollution Control, Huazhong University of Science and Technology, Wuhan, 430074, China; Key Laboratory of Water & Wastewater Treatment (MOHURD), Huazhong University of Science and Technology, Wuhan, 430074, China. Electronic address:

Degradation of tetrabromobisphenol A (TBBPA), an emerging micropollutant, by photo/Fe/sulfite process was investigated under different operational conditions and water matrices. 91% of TBBPA was efficiently degraded within 30 min in the Fe/sulfite system under sunlight irradiation when the initial pH was 6.0, which is much higher than that of TBBPA without irradiation (52%). The acceleration of radical generation and direct photolysis by photo irradiation were responsible for the enhanced TBBPA degradation. Although this process showed better performance on TBBPA degradation in weak acid conditions, the high removal efficiency was also achieved at near-neutral pH. HO, SO and direct photolysis contributed to TBBPA degradation. Direct photolysis and SO presented the dominant contribution. The degradation rate increased with elevating the Fe dose (10-40 μM), but slightly decreased when the Fe dose was further raised to 100 μM. Similarly, the degradation efficiency initially increased with increasing the sulfite dose (100-400 μM), but decreased when the sulfite concentration reached 1000 μM. Dissolved oxygen played a crucial role in TBBPA degradation, the presence of water matrices such as humic acid (0.8-4.0 mg/L), bicarbonate (0.5-10 mM) and chloride (0.5-10 mM) retarded TBBPA degradation. This study proposed a new efficient strategy to enhance TBBPA degradation in the Fe/sulfite process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.131442DOI Listing
July 2021

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen.

Crit Care 2021 07 12;25(1):243. Epub 2021 Jul 12.

Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People's Republic of China.

Background: Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class.

Methods: Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset.

Results: A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion.

Conclusions: Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-021-03682-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273991PMC
July 2021

Dissecting immune cell stat regulation network reveals biomarkers to predict ICB therapy responders in melanoma.

J Transl Med 2021 Jul 8;19(1):296. Epub 2021 Jul 8.

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Background: Immunotherapy is a revolutionary strategy in cancer therapy, but the resistance of which is one of the important challenges. Detecting the regulation of immune cells and biomarkers concerning immune checkpoint blockade (ICB) therapy is of great significance.

Methods: Here, we firstly constructed regulation networks for 11 immune cell clusters by integrating biological pathway data and single cell sequencing data in metastatic melanoma with or without ICB therapy. We then dissected these regulation networks and identified differently expressed genes between responders and non-responders. Finally, we trained and validated a logistic regression model based on ligands and receptors in the regulation network to predict ICB therapy response.

Results: We discovered the regulation of genes across eleven immune cell stats. Functional analysis indicated that these stat-specific networks consensually enriched in immune response corrected pathways and highlighted antigen processing and presentation as a core pathway in immune cell regulation. Furthermore, some famous ligands like SIRPA, ITGAM, CD247and receptors like CD14, IL2 and HLA-G were differently expressed between cells of responders and non-responders. A predictive model of gene sets containing ligands and receptors performed accuracy prediction with AUCs above 0.7 in a validation dataset suggesting that they may be server as biomarkers for predicting immunotherapy response.

Conclusions: In summary, our study presented the gene-gene regulation landscape across 11 immune cell clusters and analysis of these networks revealed several important aspects and immunotherapy response biomarkers, which may provide novel insights into immune related mechanisms and immunotherapy response prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-021-02962-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265039PMC
July 2021

Supramolecular wrapped sandwich like SW-SiN hybrid sheets as advanced filler toward reducing fire risks and enhancing thermal conductivity of thermoplastic polyurethanes.

J Colloid Interface Sci 2021 Jun 29;603:844-855. Epub 2021 Jun 29.

State Key Laboratory of Fire Science, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China. Electronic address:

A sandwich-like melamine/phytic acid/silicon nitride hybrid (SW-SiN) sheets were prepared by supramolecular wrapping as the hybrid flame retardants for thermoplastic polyurethane (TPU). The introduction of SiN sheets as a template could not only induce the generation of two-dimensional phytic/melamine (PAMA) capping layers, but also produce the synergistic flame-retardant effect on TPU composites. Cone test showed that heat release rate (HRR), smoke production rate (SPR) and total smoke production (TSP) values of TPU were decreased obviously by adding SW-SiN. TG-IR test indicated the dramatic inhibition of aromatic compound, hydrocarbons, CO and HCN release. Besides, the thermal conductivity of composites was obviously improved by adding SW-SiN. This work may provide better reference for developing multi-functional TPU composites for diverse application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2021.06.153DOI Listing
June 2021

Risk factors analysis of persistence, progression and recurrence in vaginal intraepithelial neoplasia.

Gynecol Oncol 2021 Jul 2. Epub 2021 Jul 2.

Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Number 20, Third Section of People's South Road, Chengdu 61 0000, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu, Sichuan, China. Electronic address:

Objective: to profile patients with vaginal intraepithelial neoplasia (VAIN), to evaluate natural history and to identify risk factors for persistence, progression and recurrence.

Methods: At West China Second University Hospital, all patients with histologically confirmed VAIN over a five-year period with minimum follow-up of 6 months were retrospectively identified. Demographics, medical history and clinical information related to the diagnosis and treatment were extracted. Clinical outcomes included normalization, persistence, progression and recurrence. We evaluated risk factors by univariate and multivariate analyses.

Results: A total of 1478 patients fulfilled the inclusion criteria with a median follow-up of 14 months (range, 6-60 months). In 86.6% of patients, VAIN went into normalization, 6.4% persisted, 3.5% progressed and 3.5% recurred. Besides, 24 (7.1%) VAIN 3 patients and 4 (0.8%) progressed to cancer, accounting for 85.7% and 14.3% of cancer cases, respectively. VAIN 3 patients treated with excision yielded superior outcomes. Risk factors for persistence were HPV 16, 56, 59 and 43 infections, for progression were prior hysterectomy for cervical lesions and HPV 56 infection, for recurrence were HPV 61 infection.

Conclusion: Although VAIN will regress in most patients, there are still risks of persistence, recurrence and progression, even malignancy. Therefore, a long-term follow-up is recommended. Patients with VAIN 3 are at higher risk of progressing to cancer and excision is preferred. HPV 16, 56, 59 and 43 infections might associate with an increased risk of persistence and patients with prior hysterectomy for cervical lesions tend to progress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2021.06.027DOI Listing
July 2021

Using TIF-Seq2 to investigate association between 5´ and 3´mRNA ends.

Methods Enzymol 2021 28;655:85-118. Epub 2021 May 28.

SciLifeLab, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden. Electronic address:

The development of high-throughput technologies has revealed pervasive transcription in all genomes that have been investigated so far. This has uncovered a highly interleaved transcriptome organization involving thousands of overlapping coding and non-coding RNA isoforms that challenge our traditional definitions of genes and functional regions of the genome. In this chapter, we discuss the application of an improved Transcript Isoform Sequencing approach (TIF-Seq2) able to concurrently determine the start and end sites of individual RNA molecules. We exemplify its use for the investigation of the human transcriptome and show how it is especially well suited to discriminate between overlapping molecules and accurately define their boundaries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/bs.mie.2021.03.017DOI Listing
July 2021

Association Between Three-Dimensional Transrectal Ultrasound Findings and Tumor Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: An Observational Study.

Front Oncol 2021 4;11:648839. Epub 2021 Jun 4.

Department of Abdominal Radiation Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.

Background: There is a significant demand for the development of non-surgical methods for the evaluation of complete response to tumor therapy. Predicting ability and image quality of routine imaging has not been satisfactory. To avoid the deficiencies, we assessed the capability of three-dimensional transrectal ultrasound in predicting the response to neoadjuvant chemoradiotherapy in rectal cancer patients.

Methods: The inclusion criteria were patients with locally advanced rectal adenocarcinoma, receiving capecitabine-based neoadjuvant chemoradiotherapy, distance from anal verge (≤6 cm), clinical stage T3-4 and/or N+ without evidence of distant metastasis, and restaging ycT0-3a (T3a <5 mm) after the end of neoadjuvant chemoradiotherapy. Three-dimensional transrectal ultrasound was performed 7 weeks after neoadjuvant chemoradiotherapy to discern the patients with complete response from the others. Eight main parameters were obtained from three-dimensional transrectal ultrasound: thickness of muscularis on the residual side, thickness of contralateral muscularis, angle of residual arc, regularity of the shape, integrity of the mucosal layer, blurring of the margin, internal echo, and posterior echo. The association between tumor response and three-dimensional transrectal ultrasound parameters was analyzed, and a model was developed by logistic regression.

Results: Between 2014 and 2019, 101 patients were recruited; 72 cases received total mesorectal excision, and 29 cases underwent watch-and-wait. Among the three-dimensional transrectal ultrasound parameters, the adjusted-thickness of the muscularis (<0.01), angle of the residual arc (<0.01), and regularity of the residual shape (<0.01) were strongly associated with tumor response. In the dataset with total mesorectal excision cases (TME dataset), the residual adjusted-thickness (odds ratio [OR]=4.88, 95% confidence interval [CI]=1.44-16.6, =0.01) and regularity of the residual shape (OR=5.00, 95% CI=1.13-22.2, =0.03) were kept in the final logistic model. The area under the curve of the logistic model was 0.84. Among these parameters, residual adjusted-thickness correlated significantly with tumor response. Additionally, we observed similar results in the whole population of 101 cases (whole dataset) and in the cross-validation.

Conclusion: Three-dimensional transrectal ultrasound model is a valuable method for predicting tumor response in rectal cancer patients undergoing neoadjuvant chemoradiotherapy, which should be included as a factor for evaluating clinical complete response.

Trial Registration: This trial was registered with ClinicalTrials.gov, number NCT02605265. Registered 9 November 2015 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT02605265.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.648839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223675PMC
June 2021

Molybdenum disulfide (MoS): A novel activator of peracetic acid for the degradation of sulfonamide antibiotics.

Water Res 2021 May 26;201:117291. Epub 2021 May 26.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

Sulfonamide antibiotics (SAs) are typical antibiotics and have attracted increasing concerns about their wide occurrence in environment as well as potential risk for human health. In this study, we applied a novel advanced oxidation process in SAs degradation by combining molybdenum sulfide and peracetic acid (MoS/PAA). Reactive oxygen species (ROS) including HO, CHC(O)O, CHC(O)OO, and O were generated from PAA by MoS activation and contributed to SAs degradation. The effects of initial pH, the dosages of PAA and MoS, and humic acid for SAs degradation were further evaluated by selecting sulfamethoxazole (SMX) as a target SA in the MoS/PAA process. Results suggested that the optimum pH for SMX removal was 3, where the degradation efficiency of SMX was higher than 80% after reaction for 15 min. Increasing PAA (0.075-0.45 mM) or MoS (0.1-0.4 g/L) dosages facilitated the SMX degradation, while the presence of humic acids retarded the SMX removal. This MoS/PAA process also showed good efficiencies in removing other SAs including sulfaguanidine, sulfamonomethoxine and sulfamerazine. Their possible degradation pathways were proposed based on the products identification and DFT calculation, showing that apart from the oxidation of amine groups to nitro groups in SAs, MoS/PAA induced SO extrusion reaction for SAs that contained six-membered heterocyclic moieties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.watres.2021.117291DOI Listing
May 2021

Sandwiched Cathodes Assembled from CoS -Modified Carbon Clothes for High-Performance Lithium-Sulfur Batteries.

Adv Sci (Weinh) 2021 Jun 2:e2101019. Epub 2021 Jun 2.

School of Materials Science and Engineering, China University of Petroleum, Qingdao, Shandong, 266580, P. R. China.

Structural design of advanced cathodes is a promising strategy to suppress the shuttle effect for lithium-sulfur batteries (LSBs). In this work, the carbon cloth covered with CoS nanoparticles (CC-CoS ) is prepared to function as both three-dimensional (3D) current collector and physicochemical barrier to retard migration of soluble lithium polysulfides. On the one hand, the CC-CoS film works as a robust 3D current collector and host with high conductivity, high sulfur loading, and high capability of capturing polysulfides. On the other hand, the 3D porous CC-CoS film serves as a multifunctional interlayer that exhibits efficient physical blocking, strong chemisorption, and fast catalytic redox reaction kinetics toward soluble polysulfides. Consequently, the [email protected]/[email protected] cell with a sulfur loading of 1.2 mg cm exhibits a high rate capability (≈823 mAh g at 4 C) and delivers excellent capacity retention (a decay of ≈0.021% per cycle for 1000 cycles at 4 C). Moreover, the sandwiched cathode of CC-CoS @S/[email protected] is designed for high sulfur loading LSBs. The CC-CoS @S/[email protected] cells with sulfur loadings of 4.2 and 6.1 mg cm deliver high reversible capacities of 1106 and 885 mAh g , respectively, after 100 cycles at 0.2 C. The outstanding electrochemical performance is attributed to the sandwiched structure with active catalytic component.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202101019DOI Listing
June 2021

Spata2 Knockdown Exacerbates Brain Inflammation via NF-κB/P38MAPK Signaling and NLRP3 Inflammasome Activation in Cerebral Ischemia/Reperfusion Rats.

Neurochem Res 2021 Sep 1;46(9):2262-2275. Epub 2021 Jun 1.

Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Brain inflammation induced by ischemic stroke is an important cause of secondary brain injury. The nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and NLRP3 inflammasome signaling are believed to drive the progression of brain inflammation. Spermatogenesis-associated protein2 (SPATA2) functions as a partner protein that recruits CYLD, a negative regulator of NF-κB signaling, to signaling complexes. However, the role of SPATA2 in the central nervous system remains unclear and whether it is involved in regulating inflammatory responses remains controversial. Rats were subjected to transient middle cerebral artery occlusion followed by reperfusion (tMCAO/R) surgery. The expression and localization of SPATA2 in the brain were investigated. The lentivirus-mediated shRNA was employed to inhibit SPATA2 expression. The inflammatory responses and outcomes of Spata2 knockdown were investigated. SPATA2 was co-localized with CYLD in neurons. SPATA2 expression was reduced in tMCAO/R rats. Spata2 knockdown resulted in increased microglia, increased expression of Tnfa, Il-1β, and Il-18, decreased Garcia score, and increased infarct volume. Spata2 knockdown resulted in the activation of P38MAPK and NLRP3 inflammasome and the increased activation of NF-κB signaling. These results suggest that SPATA2 plays a protective role against brain inflammation induced by ischemia/reperfusion injury. Therefore, SPATA2 could be a potential therapeutic target for treating ischemic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11064-021-03360-8DOI Listing
September 2021

Evaluating global ecosystem water use efficiency response to drought based on multi-model analysis.

Sci Total Environ 2021 Jul 11;778:146356. Epub 2021 Mar 11.

State Key Laboratory of Urban and Regional Ecology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; College of Resources and Environment, University of Chinese Academy of Sciences, China.

Drought has serious consequences on terrestrial ecosystems, particularly for their carbon and water processes. As an important indicator to examine the balance of ecosystem water and carbon cycles, ecosystem water use efficiency (WUE) has been widely used to investigate ecosystem responses to drought. However, the response of WUE to drought and the role of different ecosystem processes in controlling the response of WUE to drought are not well studied. In this paper, we used four WUE datasets from different remote sensing-driven (RS-driven) models and three drought indices (Standardized Precipitation Evapotranspiration Index, soil moisture anomaly index and water storage anomaly-based drought index) to comprehensively investigate the response of WUE to drought and its dominant ecosystem processes during the period of 2001-2018. The results showed the WUE datasets from four different RS-driven models had discrepancies in WUE temporal trends, particularly in tropical and subtropical forest and semi-arid regions. The Spearman correlation analysis revealed that the positive correlations between WUE and drought accounted for more than half of global vegetated lands, while negative relationship mainly occurred in the high latitude regions. We further explored the dominant ecosystem processes (represented by GPP and ET) in controlling WUE response to drought, and found ET controlled WUE-drought relationship in the high latitude areas and semi-arid/sub-humid regions, while GPP dominated it in tropical forest regions. Additionally, the effects of GPP and ET on controlling WUE response to drought were examined to change with different drought indices, especially in the semi-arid regions. Our study suggests multi-model analysis tend to reduce uncertainties in analyzing WUE response to drought caused by a single WUE data. Moreover, our results highlight the different role of ecosystem processes in controlling WUE response to drought and provide new information for the underlying mechanism of drought impacts on ecosystem water and carbon cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2021.146356DOI Listing
July 2021

and the Volatile of Attenuate Chronic Myocardial Ischemia Injury in a Pig Model: A Metabonomic Approach for the Mechanism Study.

Oxid Med Cell Longev 2021 28;2021:8840896. Epub 2021 Apr 28.

National Drug Clinical Trial Institute, The Second Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang 712000, China.

(SM) coupled with (DO) has been used to relieve cardiovascular diseases in China for many years. Our previous studies have integrated that SM-the volatile oil of DO (SM-DOO)-has a cardioprotective effect on chronic myocardial ischemia based on a pharmacological method, but the cardioprotective mechanism has not been elucidated completely in the metabonomic method. In the present study, a metabonomic method based on high-performance liquid chromatography time-of-flight mass spectrometry (HPLC-Q-TOF-MS) was performed to evaluate the effects of SM-DOO on chronic myocardial ischemia induced by an ameroid constrictor, which was placed on the left anterior descending coronary artery (LAD) of pigs. Pigs were divided into three groups: sham, model, and SM-DOO group. With multivariate analysis, a clear cluster among the different groups was obtained and the potential biomarkers were recognized. These biomarkers were mainly related to energy metabolism, glucose metabolism, and fatty acid metabolism. Furthermore, the protein expressions of phosphorylated AMP-activated protein kinase (p-AMPK) and glucose transporter-4 (GLUT4) were significantly upregulated by SM-DOO. The result indicated that SM-DOO could regulate the above biomarkers and metabolic pathways, especially energy metabolism and glucose metabolism. By analyzing and verifying the biomarkers and metabolic pathways, further understanding of the cardioprotective effect of SM-DOO with its mechanism was evaluated. Metabonomic is a reliable system biology approach for understanding the cardioprotective effects of SM-DOO on chronic myocardial ischemia and elucidating the mechanism underlying this protective effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8840896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099511PMC
April 2021

Flame-Retardant ADP/PEO Solid Polymer Electrolyte for Dendrite-Free and Long-Life Lithium Battery by Generating Al, P-rich SEI Layer.

Nano Lett 2021 May 11;21(10):4447-4453. Epub 2021 May 11.

State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei, Anhui 230026, China.

The poly(ethylene oxide) solid polymer electrolyte (PEO SPE) has recently received much attention, however, the organic components in the SPE are still flammable. In this paper, we find that the high efficiency halogen-free aluminum (Al) diethyl hypophosphite flame retardant (ADP) is effective in reducing the flammability of PEO SPE. The SEI layer containing Al and phosphorus (P) inhibits the growth of lithium dendrite and enhances the cycle life of the battery. The capacity of a LiFePO/SPE/Li battery containing ADP is still 123.2 mAh g at 1.0 C and the Coulombic efficiency is as high as 99.95% after 1000 cycles (60 °C). At the same time, Al, P-rich SEI can inhibit the growth of lithium dendrite and the cycle stability of the battery is further enhanced.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.nanolett.1c01137DOI Listing
May 2021

Cholesterol was identified as a biomarker in human melanocytic nevi using DESI and DESI/PI mass spectrometry imaging.

Talanta 2021 Aug 29;231:122380. Epub 2021 Mar 29.

National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, 230029, China. Electronic address:

The rapid differentiation between diseased tissue and healthy normal tissue is of great importance for the intraoperative diagnosis. Herein, desorption electrospray ionization (DESI) and DESI/post-photoionization (DESI/PI) mass spectrometry imaging were combined to in situ visualize the distribution of biochemicals within the tissue regions of human melanocytic nevi under the ambient condition with a spatial resolution of around 200 μm. Plenty of polar and nonpolar lipids were found to be specifically distributed in melanocytic nevi with statistical significance and could be used to differentiate the healthy normal tissue and melanocytic nevi. Cholesterol was further confirmed to be a potential biomarker for melanocytic nevi diagnosis by multivariate statistical analysis and immunohistochemistry of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and translocator protein (TSPO) enzymes. This work provides a visual way for the diagnosis of human melanocytic nevi by lipid profiling, which benefits the understanding of the pathological mechanism of melanocytic nevi and provides a new insight to control melanin growth from the synthesis, transport, and metabolism of cholesterol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.talanta.2021.122380DOI Listing
August 2021

Impact of Electrostatic Interaction on Bulk Morphology in Efficient Donor-Acceptor Photovoltaic Blends.

Angew Chem Int Ed Engl 2021 Jul 7;60(29):15988-15994. Epub 2021 Jun 7.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Bulk heterojunctions comprising mixed donor (D) and acceptor (A) materials have proven to be the most efficient device structures for organic photovoltaic (OPV) cells. The bulk morphology of such cells plays a key role in charge generation, recombination, and transport, thus determining the device performance. Although numerous studies have discussed the morphology-performance relationship of these cells, the method of designing OPV materials with the desired morphology remains unclear. Herein, guided by molecular electrostatic potential distributions, we have established a connection between the chemical structure and bulk morphology. We show that the molecular orientation at the D-A interface and the domain purity in the blend can be effectively modulated by modifying the functional groups. Enhancing the D-A interaction is beneficial for charge generation. However, the resulting low domain purity and increased charge transfer ratio in its hybridization with the local excitation states lead to severe charge recombination. Fine-tuning the bulk morphology can give balanced charge generation and recombination, which is crucial for further boosting the efficiency of the OPV cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202102622DOI Listing
July 2021

A New Conjugated Polymer that Enables the Integration of Photovoltaic and Light-Emitting Functions in One Device.

Adv Mater 2021 Jun 25;33(22):e2101090. Epub 2021 Apr 25.

Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Exploring the intriguing bifunctional nature of organic semiconductors and investigating the feasibility of fabricating bifunctional devices are of great significance in realizing various applications with one device. Here, the design of a new wide-bandgap polymer named PBQx-TCl (optical bandgap of 2.05 eV) is reported, and its applications in photovoltaic and light-emitting devices are studied. By fabricating devices with nonfullerene acceptors BTA3 and BTP-eC9, it is shown that the devices exhibit a high power conversion efficiency (PCE) of 18.0% under air mass 1.5G illumination conditions and an outstanding PCE of 28.5% for a 1 cm device and 26.0% for a 10 cm device under illumination from a 1000 lux light-emitting diode. In addition, the PBQx-TCl:BTA3-based device also demonstrates a moderate organic light-emitting diode performance with an electroluminescence external quantum efficiency approaching 0.2% and a broad emission range of 630-1000 nm. These results suggest that the polymer PBQx-TCl-based devices exhibit outstanding photovoltaic performance and potential light-emitting functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202101090DOI Listing
June 2021

Social Support and Mortality in Community-Dwelling Chinese Older Adults: The Mediating Role of Frailty.

Risk Manag Healthc Policy 2021 16;14:1583-1593. Epub 2021 Apr 16.

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China.

Purpose: Population ageing is posing an unprecedented challenge globally, necessitating a better understanding of modifiable factors and underlying pathways that could contribute to health and longevity in older age. We thus aim to investigate how the modifiable social support (and its various sources) is related to mortality among older adults, as well as whether and to what extent geriatric frailty plays a role in mediating the relationship.

Methods: We included 11,934 community-dwelling adults (≥65) from four waves of the Chinese Longitudinal Healthy Longevity Survey (2008-2018). Frailty was constructed by 44 health deficits, following a validated frailty index scale. Social support was measured using a sum score of three dimensions (family support, social service and social security) with 22 items. The outcome was all-cause mortality. Multivariate logistic or linear regression models were employed when appropriate to assess the associations among social support, frailty and mortality. Mediation analysis was applied to examine the role of frailty underlying the pathway between social support and mortality risk.

Results: A higher sum score of social support at baseline reduced mortality risk during the 10-year follow-up period (AOR=0.947, 95% CI=0.917~0.977). Amongst three sources of social support, family support and social security availability showed significantly protective effect against mortality, while social service revealed only non-significant effect. A higher level in the overall social support (β=-0.066, 95% CI=-0.113~-0.020) or family support (β=-0.121, 95% CI=-0.202~-0.039) was also significantly associated with decreased frailty. Meanwhile, frailty partially mediated the relationship of mortality with the overall social support and family support, where the proportion of mediation equaled to 17.1% and 20.5%, respectively.

Conclusion: Social support could be associated with reduced risks for frailty and mortality, and such protective influences are especially manifested in its family support component among Chinese older adults. Frailty functions as potential mediator underlying the association of mortality with social support and family support. Our findings indicate the importance of social support as an integral part of geriatric care and underline the potential benefits of frailty assessment and intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S296018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057827PMC
April 2021

IRS-2/Akt/GSK-3/Nrf2 Pathway Contributes to the Protective Effects of Chikusetsu Saponin IVa against Lipotoxicity.

Oxid Med Cell Longev 2021 3;2021:8832318. Epub 2021 Apr 3.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an Shaanxi 710032, China.

Chronic hyperlipidemia leads to pancreatic -cell apoptosis and dysfunction through inducing oxidative stress. Chikusetsu saponin IVa (CHS) showed antioxidant and antidiabetic properties in our previous studies; however, its protective effects against lipotoxicity-induced -cell oxidative stress and dysfunction are not clear. This study was designed to investigate the effects of CHS against lipotoxicity-induced -cell injuries and its possible mechanism involved. High-fat (HF) diet and a low dose of streptozotocin- (STZ-) induced type 2 diabetes mellitus (T2DM) model and TC3 cells subjected to 0.5 mM palmitate (PA) to imitate the lipotoxic model were performed. Pancreatic functions, ROS, and antioxidant protein measurements were performed to evaluate the effects of CHS on cell injuries. Protein expression levels were measured by Western blotting. Furthermore, siRNA-targeted Nrf2, PI3K/Akt inhibitor (LY294002), or GSK-3 inhibitor (LiCl) was used to investigate the crosstalk relationships between proteins. As the results showed, CHS treatment inhibited apoptosis, promoted insulin release, and reduced oxidative stress. CHS treatment significantly increased the expression of Nrf2 in the cytoplasm and nuclear protein. The antioxidative and benefit effects of CHS were inhibited by siNrf2. The phosphorylation of IRS-2, PI3K, Akt, and GSK-3 was markedly increased by CHS which were inhibited by PA. In addition, inhibition of PI3K/Akt or GSK-3 with specific inhibitors dramatically abrogated the protective effects of CHS, revealing that the IRS-2/Akt/GSK-3 signaling axis was involved in the protective effects of CHS. These results demonstrate that CHS protected TC3 cells against PA-induced oxidative stress and cell dysfunction through Nrf2 by the IRS-2/Akt/GSK-3-mediated pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/8832318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041533PMC
May 2021

Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH.

Cell Rep 2021 Apr;35(3):108992

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, PRC; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, PRC. Electronic address:

Plant-nectar-derived sugar is the major energy source for mosquitoes, but its influence on vector competence for malaria parasites remains unclear. Here, we show that Plasmodium berghei infection of Anopheles stephensi results in global metabolome changes, with the most significant impact on glucose metabolism. Feeding on glucose or trehalose (the main hemolymph sugars) renders the mosquito more susceptible to Plasmodium infection by alkalizing the mosquito midgut. The glucose/trehalose diets promote proliferation of a commensal bacterium, Asaia bogorensis, that remodels glucose metabolism in a way that increases midgut pH, thereby promoting Plasmodium gametogenesis. We also demonstrate that the sugar composition from different natural plant nectars influences A. bogorensis growth, resulting in a greater permissiveness to Plasmodium. Altogether, our results demonstrate that dietary glucose is an important determinant of mosquito vector competency for Plasmodium, further highlighting a key role for mosquito-microbiota interactions in regulating the development of the malaria parasite.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.108992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116483PMC
April 2021

The Microbiota of Three Anopheles Species in China.

J Am Mosq Control Assoc 2021 03;37(1):38-40

Microbiota are vital for the development, physiology, and vectorial capacity of mosquitoes. The composition and role of microbiota in Anopheles species, especially Anopheles gambiae and Anopheles stephensi, have been extensively studied, but little is known about the microbiota of Anopheles species in China. We characterized the microbial communities of Anopheles dirus, Anopheles sinensis, and Anopheles lesteri by 16S rRNA sequencing. There were distinct differences in the composition of microbiota in An. lesteri and the other 2 species. The discriminatory genera in the 3 species were analyzed by the linear discriminant analysis effect size method. Our results provide an overview of the population structure of microbiota in 3 native Anopheles species and will pave the way for further understanding of their role in mosquito physiology and vector competence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2987/20-6940DOI Listing
March 2021

Comparative Study of Cytotoxicity, DNA Damage and Oxidative Stress Induced by Heavy Metals Cd(II), Hg(II) and Cr(III) in Yeast.

Curr Microbiol 2021 May 26;78(5):1856-1863. Epub 2021 Mar 26.

Department of Wine, Food and Molecular Biosciences, Lincoln University, Lincoln, Canterbury, 7647, New Zealand.

Wide range of applications of heavy metals and improperly discarded their castoffs possess serious threats to environment and human health. In this study, cytotoxicity, DNA damage and oxidative stress induced by Cd(II), Hg(II) and Cr(III) were comparatively studied in yeast Saccharomyces cerevisiae. Cd(II), Hg(II), and Cr(III) all produced strong cytotoxicity resulting in growth inhibition and cell mortality to varying degrees (Hg(II) > Cd(II) > Cr(III)). Hg(II) produced more oxidative stress. Cr(III) caused more serious DNA damage in vitro. Cd(II) also caused both obvious DNA damage and oxidative stress at higher concentration, but not as efficiently as Cd(II) and Hg(II). A further null mutation sensitivity assay showed that the relative sensitivity of rad1∆ to the metals was Cr(III) > Cd(II) > Hg(II), and that of trx1∆ to the metals was Hg(II) > Cd(II) > Cr(III). These data provide a clear evidence that the Cr(III) can cause significant DNA damage and potential genotoxicity; Hg(II) can strongly inhibit SOD activity, produce lipid peroxidation and cause serious membrane injury, suggesting these heavy metals can cause different toxic effects in different ways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00284-021-02454-4DOI Listing
May 2021

Rhein protects 5/6 nephrectomized rat against renal injury by reducing inflammation via NF-κB signaling.

Int Urol Nephrol 2021 Jul 25;53(7):1473-1482. Epub 2021 Mar 25.

Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, 127 Changlexi Street, Xi׳an, 710032, Shaanxi, China.

Background/aims: Inflammation is well known to play a pivotal role in renal injury. Rhein is a major component of the medicinal Rhubarb. The aim of this study was to investigate whether Rhein protects against renal injury and explore its underlying mechanism.

Methods: 5/6 nephrectomization (5/6 Nx) was operated on Sprague-Dawley rats. Human kidney tubular epithelial (HK-2) cells were treated with lipopolysaccharide (LPS). The level of blood urea nitrogen (BUN) and serum creatinine (SCr) was examined. Kidney tissues were stained with hematoxylin and eosin to check the morphology. The cell viability was examined. The levels of cytokines and chemokines were measured by ELISA kit. The protein expression was determined by western blot.

Results: Rhein significantly decreased SCr and BUN levels in 5/6 Nx rat. The morphologic findings indicated noteworthy amelioration of the damaged renal tissue in Rhein-treated rats. Rhein significantly protects HK-2 cells from LPS-mediated apoptosis. The productions of inflammatory signaling molecules (TNF-α, IL-6 and MCP-1) were inhibited by Rhein. LPS-induced NF-κB activation was also attenuated by Rhein via blocking its nuclear translocation by inhibiting phosphorylation of IκBα.

Conclusion: These findings provide evidence that Rhein protect against renal injury, and NF-κB signaling pathway is involved in this protective effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-020-02739-wDOI Listing
July 2021

Lyciumamide A, a dimer of phenolic amide, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro.

J Mol Histol 2021 Jun 23;52(3):449-459. Epub 2021 Mar 23.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.

Currently, the excessive activation of N-methyl-D-aspartate receptors (NMDARs) is considered to be a crucial mechanism of brain injury. Lycium barbarum A (LyA) is a dimer of phenol amides isolated from the fruit of Lycium barbarum. Our previous studies have shown that LyA has potential antioxidant activity. This study aimed to explore the neuroprotective effect of LyA and its potential mechanism. Firstly, the molecular docking was used to preliminarily explore the potential function of LyA to block NMDAR. Then, the ability of LyA was further verified by NMDA-induced human neuroblastoma SH-SY5Y cells in vivo. Treatment with LyA significantly attenuated NMDA-induced neuronal insults by increasing cell viability, reducing lactate dehydrogenase (LDH) release, and increasing cell survival. Meanwhile, LyA significantly reversed the increase in intracellular calcium and in ROS production induced by NMDA. Finally, the western blot indicated that LyA could suppress the Ca influx and increase the p-NR2B, p-CaMKII, p-JNK, and p-p38 level induced by NMDA. These above findings provide evidence that LyA protect against brain injury, and restraining NMDARs and suppressing mitochondrial oxidative stress and inhibiting cell apoptosis may be involved in the protective mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10735-020-09952-yDOI Listing
June 2021

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study.

Cancer Biol Med 2021 Mar 23. Epub 2021 Mar 23.

Department of Hematology, Peking Union Medical College Hospital, Beijing 100730, China.

Objective: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL).

Methods: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS).

Results: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable.

Conclusions: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0413DOI Listing
March 2021

A Yeast-Based Drug Discovery Platform To Identify Plasmodium falciparum Type II NADH Dehydrogenase Inhibitors.

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing, China

Conventional methods utilizing protein activity assay or parasite survival to screen for malaria inhibitors suffer from high experimental background and/or inconvenience. Here, we introduce a yeast-based system to facilitate chemical screening for specific protein or pathway inhibitors. The platform comprises several isogeneic strains that differ only in the target of interest, so that a compound which inhibits one strain but not the other is implicated in working specifically against the target. We used NDH2 (PfNDH2), a type II NADH dehydrogenase, as a proof of principle to show how well this works. Three isogenic strains harboring, respectively, exogeneously introduced PfNDH2, its own complex I (a type I NADH dehydrogenase), and PfNDH2 with its own complex I, were constructed. In a pilot screen of more than 2,000 compounds, we identified a highly specific inhibitor that acts on PfNDH2. This compound poorly inhibits the parasites at the asexual blood stage; however, is highly effective in repressing oocyst maturation in the mosquito stage. Our results demonstrate that the yeast cell-based screen platform is feasible, efficient, economical, and has very low background noise. Similar strategies could be extended to the functional screen for interacting molecules of other targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.02470-20DOI Listing
May 2021

Polyethylenimine quantity and molecular weight influence its adjuvanting properties in liposomal peptide vaccines.

Bioorg Med Chem Lett 2021 05 9;40:127920. Epub 2021 Mar 9.

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia. Electronic address:

We recently reported that polyethylenimine (PEI; molecular weight of 600 Da) acted as a vaccine adjuvant for liposomal group A Streptococcus (GAS) vaccines, eliciting immune responses in vivo with IgG antibodies giving opsonic activity against five Australian GAS clinical isolates. However, to date, no investigation comparing the structure-activity relationship between the molecular weight of PEI and its adjuvanting activity in vaccine development has been performed. We hypothesized that the molecular weight and quantity of PEI in a liposomal vaccine will impact its adjuvanting properties. In this study, we successfully formulated liposomes containing different molecular weights of PEI (600, 1800, 10k and 25k Da) and equivalents of PEI (0.5, 1 and 2) of branched PEI. Outbred mice were administrated the vaccine formulations intranasally, and the mice that received a high ratio of PEI 600 reported a stronger immune response than the mice that received a lower ratio of PEI 600. Interestingly, mice that received the same quantity of PEI 600, PEI 10k and PEI 25k showed similar immune responses in vivo and in vitro. This comparative study highlights the ratio of PEI present in the liposome vaccines impacts adjuvanting activity, however, PEI molecular weight did not significantly enhance its adjuvanting properties. We also report that the stability of PEI liposomes is critical for vaccines to elicit the desired immune response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2021.127920DOI Listing
May 2021

Frailty Predicts Increased Health Care Utilization Among Community-Dwelling Older Adults: A Longitudinal Study in China.

J Am Med Dir Assoc 2021 Mar 2. Epub 2021 Mar 2.

Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, China; Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China. Electronic address:

Objectives: Frailty, a multidimensional syndrome characterized by vulnerability to stressors, is an emerging public health priority with high prevalence in older adults. Frailty has been identified to predictive negative health outcomes, yet quantified evidence regarding its effect on health care systems is scarce. This study examines how frailty affects health care utilization, and explores whether these associations varied by gender.

Design: Cohort study with a 2-year follow-up.

Setting: and Participants: Data were derived from 2 waves (2011 and 2013) of the China Health and Retirement Longitudinal Study, and 3119 community-dwelling participants aged ≥60 years were analyzed.

Methods: Frailty was assessed by a validated frailty phenotype scale, and measures for health care utilization were self-reported. Panel data approach of mixed-effects regression models was used to examine the associations.

Results: Longitudinal results demonstrated that compared with robustness, prefrailty and frailty were both significantly associated with increased likelihood of outpatient visit, inpatient visit, and inpatient length of stay, even after adjusting for multimorbidity in multivariate analyses (all P < .05). Every 1-component increase in frailty was also found to significantly increase the risk for health care utilization [any outpatient visit: adjusted odds ratio (OR) 1.30, 95% confidence interval (CI) 1.14-1.48; number of outpatient visits: adjusted incident rate ratio (IRR) 1.34, 95% CI 1.18-1.53; any inpatient visit: adjusted OR 1.44, 95% CI 1.22-1.71; number of inpatient visits: adjusted IRR 1.40, 95% CI 1.20-1.62; inpatient length of stay: adjusted IRR 1.50, 95% CI 1.18-1.92]. The preceding associations were similarly observed irrespective of gender.

Conclusions And Implications: Frailty is a significant predictor for increased health care utilization among community-dwelling older adults. These findings have important implications for routine clinical practice and public health investment. Early screening and intervention for potentially modifiable frailty could translate into considerable savings for households and health care systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamda.2021.01.082DOI Listing
March 2021

Total glycosides from stems of Cistanche tubulosa alleviate depression-like behaviors: bidirectional interaction of the phytochemicals and gut microbiota.

Phytomedicine 2021 Mar 22;83:153471. Epub 2021 Jan 22.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China. Electronic address:

Background: As the most frequently used kidney-yang tonifying herb in traditional Chinese medicine, dried succulent stems of Cistanche tubulosa (Schenk) Wight (CT) have been shown to be effective in the treatment of depression. However, the antidepressant components and their underlying mechanism remain unclear.

Purpose: To explore the active components of CT against depression, as well as the potential mechanisms.

Study Design And Methods: Behavioral despair tests were used to assess the antidepressant activities of polysaccharides, oligosaccharides and different glycoside-enriched fractions separated from CT, as well as the typical gut microbiota metabolites including 3-hydroxyphenylpropionic acid (3-HPP) and hydroxytyrosol (HT). Furthermore, the effects of bioactive fractions and metabolites on chronic unpredictable mild stress (CUMS) model were explored with multiple pharmacodynamics and biochemical analyses. Changes in colonic histology and the intestinal barrier were observed by staining and immunohistochemical analysis. Gut microbial features and tryptophan-kynurenine metabolism were explored using 16S rRNA sequencing and western-blotting, respectively.

Results: Total glycosides (TG) dramatically alleviated depression-like behaviors compared to different separated fractions, reflecting in the synergistic effects of phenylethanoid and iridoid glycosides on the hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis, severe neuro- and peripheral inflammation, and deficiencies in 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor in the hippocampus. Moreover, TG mitigated low-grade inflammation in the colon and intestinal barrier disruption, and the abundances of several bacterial genera highly correlated with the HPA axis and inflammation in CUMS rats. Consistently, the expression of indoleamine 2, 3-dioxygenase 1 (IDO1) in the colon was significantly reduced after TG administration, accompanied by the suppression of tryptophan-kynurenine metabolism. On the other hand, HT also exerted a marked antidepressant effect by ameliorating HPA axis function, pro-inflammatory cytokine release, and tryptophan-kynurenine metabolism, while it was unable to largely adjust the disordered gut microbiota in the same manner as TG. Surprisingly, superior to fluoxetine, TG and HT could further improve dysfunction of the hypothalamic-pituitary-gonadal axis and abnormal cyclic nucleotide metabolism.

Conclusion: TG are primarily responsible for the antidepressant activity of CT; its effect might be achieved through the bidirectional interaction of the phytochemicals and gut microbiota, and reflect the advantage of CT in the treatment of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2021.153471DOI Listing
March 2021

Rapamycin inhibits pathogen transmission in mosquitoes by promoting immune activation.

PLoS Pathog 2021 02 24;17(2):e1009353. Epub 2021 Feb 24.

The State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.

Repeated blood meals provide essential nutrients for mosquito egg development and routes for pathogen transmission. The target of rapamycin, the TOR pathway, is essential for vitellogenesis. However, its influence on pathogen transmission remains to be elucidated. Here, we show that rapamycin, an inhibitor of the TOR pathway, effectively suppresses Plasmodium berghei infection in Anopheles stephensi. An. stephensi injected with rapamycin or feeding on rapamycin-treated mice showed increased resistance to P. berghei infection. Exposing An. stephensi to a rapamycin-coated surface not only decreased the numbers of both oocysts and sporozoites but also impaired mosquito survival and fecundity. Transcriptome analysis revealed that the inhibitory effect of rapamycin on parasite infection was through the enhanced activation of immune responses, especially the NF-κB transcription factor REL2, a regulator of the immune pathway and complement system. Knockdown of REL2 in rapamycin-treated mosquitoes abrogated the induction of the complement-like proteins TEP1 and SPCLIP1 and abolished rapamycin-mediated refractoriness to Plasmodium infection. Together, these findings demonstrate a key role of the TOR pathway in regulating mosquito immune responses, thereby influencing vector competence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1009353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939355PMC
February 2021

Cd bioavailability and nitrogen cycling microbes interaction affected by mixed amendments under paddy-pak choi continued planting.

Environ Pollut 2021 Apr 6;275:116542. Epub 2021 Feb 6.

Department of Soil, Water, & Climate, Univ. of Minnesota, 1991 Upper Buford Cir, Falcon Heights, MN, 55108, USA.

Cadmium (Cd) is the most concerning soil pollutant, and a threat to human health, especially in China. The in-situ immobilization of Cadmium by amendments is one of the most widely adopted methods to remedy soil contamination. The study was designed to evaluate the effect of organo-chemical amendments on soil Cd bioavailability and nitrogen cycling microbes under continuous planting of rice (Oryza sativa) and pak choi (Brassica chinensis L.). The experiment was carried out using four amendments, Lime, Zeolite, Superphosphate, and Biochar, at two different ratios; M1: at the ratio of 47:47:5:1, and M2 at the ratio of 71:23:5:1, respectively. Moreover, both M1 and M2 were enriched at four levels (T1: 0.5%; T2: 1%; T3: 2%; T4: 4%). Results showed that compared with CK (Cd enriched soils), the yield of rice under treatments of M1T1 and M2T1 increased by 8.93% and 8.36%, respectively. While the biomass (fresh weight) of pak choi under M1 and M2 amendments increased by 2.52-2.98 times and 0.76-2.89 times respectively, under enrichment treatments T1, T2, and T3. The total Cd concentrations in rice grains treated with M1T3 and M2T3 decreased by 89.25% and 93.16%, respectively, compared with CK. On the other hand, the total Cd concentrations in pak choi under M1T3 and M2T2 decreased by 92.86% and 90.23%, respectively. The results showed that soil pH was the main factor affecting Cd bioavailability in rice and pak choi. The Variance partitioning analysis (VPA) of rice and pak choi showed that soil pH was the most significant contributing factor. In the rice season, the contribution of soil pH (P) on Cd bioavailability was 10.14% (P = 0.102), and in the pak choi season, the contribution of soil pH was 8.38% (P = 0.133). Furthermore, the abundance of ammonia oxidation and denitrifying microorganisms had significantly correlation with soil pH and exchange Cd. In rice season, when the enrichment level of amendments increased from 0.5% (T1) to 2% (T3), the gene abundance of AOA, AOB, nirK, nirS and nosZ (І) tended to decrease. While in pak choi season, when the enrichment level increased at the level of 0.5% (T1), 1% (T2), and 2% (T3), the gene abundance of AOB, nirS, and nosZ (І) increased. Additionally, the gene abundance of AOA and nirK showed a reduction in the pak choi season contrasting to rice. And the mixed amendment M2 performed better at reducing Cd uptake than M1, which may have correlation with the ratio of lime and zeolite in them. Finally, we conclude that between these two amendments, when applied at a moderate level M2 type performed better than M1 in reducing Cd uptake, and also showed positive effects on both gene abundance and increase soil pH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.116542DOI Listing
April 2021
-->