Publications by authors named "Zhao Wang"

1,471 Publications

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Rapid changes in coastal ocean microbiomes uncoupled with shifts in environmental variables.

Environ Microbiol 2022 Jun 17. Epub 2022 Jun 17.

Marine Laboratory, Duke University, Beaufort, NC, USA.

Disturbances, here defined as events that directly alter microbial community composition, are commonly studied in host-associated and engineered systems. In spite of global change both altering environmental averages and increasing extreme events, there has been relatively little research into the causes, persistence and population-level impacts of disturbance in the dynamic coastal ocean. Here, we utilize 3 years of observations from a coastal time series to identify disturbances based on the largest week-over-week changes in the microbiome (i.e. identifying disturbance as events that alter the community composition). In general, these microbiome disturbances were not clearly linked to specific environmental factors and responsive taxa largely differed, aside from SAR11, which generally declined. However, several disturbance metagenomes identified increased phage-associated genes, suggesting that unexplained community shifts might be caused by increased mortality. Furthermore, a category 1 hurricane, the only event that would likely be classified a priori as an environmental disturbance, was not an outlier in microbiome composition, but did enhance a bloom in seasonally abundant phytoplankton. Thus, as extreme environmental changes intensify, assumptions of what constitutes a disturbance should be re-examined in the context of ecological history and microbiome responses.
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http://dx.doi.org/10.1111/1462-2920.16086DOI Listing
June 2022

Editorial: Multimodality Imaging in Acute Coronary Syndrome.

Front Cardiovasc Med 2022 27;9:939428. Epub 2022 May 27.

Department of Magnetic Resonance Imaging, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.3389/fcvm.2022.939428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197208PMC
May 2022

Mesenchymal stem cell-derived extracellular vesicles alleviate cervical cancer by delivering miR-331-3p to reduce LIMS2 methylation in tumor cells.

Hum Mol Genet 2022 Jun 16. Epub 2022 Jun 16.

Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin 150081, P. R. China.

This study is to investigate if extracellular vesicles (EVs) from bone marrow mesenchymal stem cells (BMSCs) deliver miR-331-3p to regulate LIMS2 methylation in cervical cancer cells. Cervical cancer cells were incubated with EVs from BMSCs with altered expression of miR-331-3p, DNMT3A or/and LIMS2 and then subjected to EdU, Transwell, flow cytometry and Western blotting analyses. Dual-luciferase reporter assay was conducted to verify the binding between miR-331-3p and DNMT3A. A xenograft model was established to evaluate the effect of BMSC-derived EV-miR-331-3p on cervical tumor growth. miR-331-3p was lowly and DNMT3A was highly expressed in cervical cancer. BMSC-derived EVs delivered miR-331-3p to control the behaviors of cervical cancer cells. miR-331-3p inhibited the expression of DNMT3A by binding DNMT3A mRNA. DNMT3A promoted LIMS2 methylation and reduced the expression of LIMS2. Overexpression of DNMT3A or silencing of LIMS2 in BMSCs counteracted the tumor suppressive effects of miR-331-3p. BMSC-derived EV-miR-331-3p also inhibited the growth of cervical tumors in vivo. BMSC-derived EVs alleviate cervical cancer partially by delivering miR-331-3p to reduce DNMT3A-dependent LIMS2 methylation in tumor cells.
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http://dx.doi.org/10.1093/hmg/ddac130DOI Listing
June 2022

Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection.

iScience 2022 Jun 23;25(6):104447. Epub 2022 May 23.

Department of Cardiovascular Diseases, Physiology and Biomedical Engineering, Center for Regenerative Medicine, Mayo Clinic Arizona, 13400 E Shea Blvd, Scottsdale, AZ, USA 85259.

Acute myocardial infarction is a leading cause of death worldwide. We have previously identified two cardioprotective molecules - FGF1 and CHIR99021- that confer cardioprotection in mouse and pig models of acute myocardial infarction. Here, we aimed to determine if improved myocardial metabolism contributes to this cardioprotection. Nanofibers loaded with FGF1 and CHIR99021 were intramyocardially injected to ischemic myocardium of adult mice immediately following surgically induced myocardial infarction. Animals were euthanized 3 and 7 days later. Our data suggested that FGF1/CHIR99021 nanofibers enhanced the heart's capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium. The impact of FGF1/CHIR99021 on metabolism was more obvious in the first three days post myocardial infarction. Taken together, these findings suggest that FGF1/CHIR99021 protects the heart against ischemic injury via improving myocardial metabolism which may be exploited for treatment of acute myocardial infarction in humans.
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http://dx.doi.org/10.1016/j.isci.2022.104447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189130PMC
June 2022

Synthesis of bio-based polyester elastomers and evaluation of their biocompatibility and biodegradability as biomedical materials.

Biomater Sci 2022 Jun 14. Epub 2022 Jun 14.

Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

Biodegradable polyester elastomers have found wide application in the tissue engineering field. In this study, an all bio-based polyester elastomer (BPE) is synthesized from five bio-based monomers; and the biodegradability and biocompatibility of the BPE are first evaluated using a subcutaneous mouse model, aiming to investigate its potential application as a soft tissue repair material. The biodegradation property of the BPE in the subcutaneous part of the back region of mice is systematically studied by monitoring the mass loss and the morphological change of the BPE over different times. It is found that the mass loss increases with increasing time, and the mass loss reaches more than 25% after implantation for 24 weeks. From the scanning electron microscope results, the BPE shows surface degradation behavior, which would be beneficial for maintaining their structural integrity until later stages of degradation and be suitable for biomedical application. Furthermore, after subcutaneous implantation of the BPE, the blood and urine routine indexes remain within normal ranges and histology of the major organs shows no abnormalities in H&E staining analysis, which indicates the excellent biocompatibility of the BPE.
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http://dx.doi.org/10.1039/d2bm00436dDOI Listing
June 2022

Microenergy acoustic pulse therapy restores function and structure of pelvic floor muscles after simulated birth injury.

Transl Androl Urol 2022 May;11(5):595-606

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.

Background: The mechanisms of the microenergy acoustic pulse (MAP) therapy on restoring structure and function of pelvic floor muscles (PFM) after simulated birth injury are not well understood.

Methods: A total 24 female Sprague-Dawley rats were randomly grouped into sham control (sham), vaginal balloon dilation and ovariectomy (VBDO), VBDO + β-aminopropionitrile (BAPN, an irreversible LOX inhibitor), and VBDO + BAPN and treated with MAP (n=6 in each group). The MAP therapy was administered 2 times per week for 4 weeks with 1-week washout, the functional and histological studies were conducted in all 24 rats. The viscoelastic behavior of the PFM, including iliococcygeus (IC) and pubococcygeus (PC), was examined with a biomechanical assay. The structure of the PFM was assessed by immunofluorescence and Masson's trichrome staining.

Results: The leak point pressure (LPP) assay demonstrated that the MAP therapy group had higher LPPs compared to that of VBDO and BAPN groups. In the sham group, the muscular stiffness (K) of IC muscle was significantly higher than that of PC muscle while the pelvic floor muscle rebound activity (MRA) of PC muscle was stronger than that of IC muscle (291.26±45.33 and 241.18±14.23 N/cm, respectively). Both VBDO and BAPN decreased the MRA and increased the K in both IC and PC. Histologic examination revealed increased fibrous tissue (collagen) and degeneration of muscle fibers in both VBDO and BAPN groups. MAP therapy significantly reduced the collagen content and improved the architecture of muscle fibers.

Conclusions: MAP appears to restore the structure and function of PFM by regenerating muscular fibers and improving biomechanical properties in an animal model of simulated birth injury.
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http://dx.doi.org/10.21037/tau-22-30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177267PMC
May 2022

Niche Partitioning of Labyrinthulomycete Protists Across Sharp Coastal Gradients and Their Putative Relationships With Bacteria and Fungi.

Front Microbiol 2022 24;13:906864. Epub 2022 May 24.

Center for Marine Environmental Ecology, School of Environmental Science and Engineering, Tianjin University, Tianjin, China.

While planktonic microbes play key roles in the coastal oceans, our understanding of heterotrophic microeukaryotes' ecology, particularly their spatiotemporal patterns, drivers, and functions, remains incomplete. In this study, we focus on a ubiquitous marine fungus-like protistan group, the Labyrinthulomycetes, whose biomass can exceed that of bacterioplankton in coastal oceans but whose ecology is largely unknown. Using quantitative PCR and amplicon sequencing of their 18S rRNA genes, we examine their community variation in repeated five-station transects across the nearshore-to-offshore surface waters of North Carolina, United States. Their total 18S rRNA gene abundance and phylotype richness decrease significantly from the resource-rich nearshore to the oligotrophic offshore waters, but their Pielou's community evenness appears to increase offshore. Similar to the bacteria and fungi, the Labyrinthulomycete communities are significantly structured by distance from shore, water temperature, and other environmental factors, suggesting potential niche partitioning. Nevertheless, only several Labyrinthulomycete phylotypes, which belong to aplanochytrids, thraustochytrids, or unclassified Labyrinthulomycetes, are prevalent and correlated with cohesive bacterial communities, while more phylotypes are patchy and often co-occur with fungi. Overall, these results complement previous time-series observations that resolve the Labyrinthulomycetes as persistent and short-blooming ecotypes with distinct seasonal preferences, further revealing their partitioning spatial patterns and multifaceted roles in coastal marine microbial food webs.
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http://dx.doi.org/10.3389/fmicb.2022.906864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171235PMC
May 2022

Rational assembly of RGD/MoS/Doxorubicin nanodrug for targeted drug delivery, GSH-stimulus release and chemo-photothermal synergistic antitumor activity.

J Photochem Photobiol B 2022 May 31;233:112487. Epub 2022 May 31.

Pharmaceutical Analysis Division, School of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China. Electronic address:

Herein, we present the facile design and construction of a nanodrug system integrating targeted drug delivery and synergistic chemo-photothermal antitumor activity. MoS nanosheets were synthesized and modified by αβ integrin binding peptide (Arg-Gly-Asp, RGD) using lipoic acid functionalized polyethylene glycol (LA-PEG-COOH), forming a well dispersed and targeted delivery nanocarrier. Further, covalent coupling of antitumor drug, thiolated doxorubicin (DOX) via disulfide linkage resulted in a novel nanodrug, RGD/MoS/DOX. The prepared nanocarrier showed favorable stability, biocompatibility and photothermal conversion efficiency. Fluorescence imaging revealed that Hela cells could endocytose far more nanodrug than H9c2 normal myocardial cells due to the targeted delivery characteristic. Particularly, GSH-induced disulfide bond cleavage facilitated the effective release of DOX from the nanodrug in the tumor microenvironment. The survival rate of Hela cells incubated with the nanodrug for 48 h was 22.2 ± 1.2%, which dramatically reduced to 8.9 ± 1.4% in combination with 808 nm NIR irradiation, demonstrating powerful photothermal induced tumor-killing efficacy. In contrast, the survival rates of H9c2 cells treated by the nanodrug and free DOX were 68.5 ± 2.6% and 6.7 ± 2.6%, respectively, an indication of the notably alleviated cardiotoxicity of the designed nanodrug. The cell apoptosis experiment further verified the synergistic chemo-photothermal effect, thus paving a way toward design of high-efficiency and low-toxicity antitumor nanodrug.
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http://dx.doi.org/10.1016/j.jphotobiol.2022.112487DOI Listing
May 2022

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial.

Signal Transduct Target Ther 2022 Jun 6;7(1):172. Epub 2022 Jun 6.

Lanzhou Institute of Biological Products Company Limited, Lanzhou, China.

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1-3 months, 4-6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01-63.85 folds on day 28 after vaccination, whereas only 4.20-16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.
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http://dx.doi.org/10.1038/s41392-022-00984-2DOI Listing
June 2022

Insulin resistance enhances binge ethanol-induced liver injury through promoting oxidative stress and up-regulation CYP2E1.

Life Sci 2022 Aug 2;303:120681. Epub 2022 Jun 2.

Department of Toxicology, the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, The Fourth Military Medical University, Xi'an, 710032, PR China. Electronic address:

Alcoholic liver disease (ALD) has caused a serious burden on public and personal health in crowd with ethanol abuse. The effects of insulin resistance (IR) on ALD and the mechanisms underlying these responses are still not well understood. In this study, we investigated the changes of liver injury, inflammation, apoptosis, mitochondrial dysfunction and CYP2E1 changes in liver of mice exposed to ethanol with IR or not. We found IR increased the sensitivity of liver injury in mice exposed to ethanol, manifested as the increase serum activities of AST and ALT, the accumulation of triglycerides, the deterioration of liver pathology and increase of inflammatory factors. IR also exacerbated apoptosis and mitochondrial dysfunction in liver of mice exposed to ethanol. The increase of oxidative stress and the decrease of antioxidant defense ability might be responsible for the sensitizing effects of IR on ethanol-induced liver injury, supported by the increase of MDA levels and the decline of GSH/GSSG, the inactivation of antioxidant enzymes SOD, GR through the inhibition of Nrf-2 pathway. The activation of CYP2E1 might be also involved in the sensitizing effects of IR on ethanol induced liver injury in mice. These results demonstrated that IR exhibited a significant pro-oxidative and pro-apoptosis effects to aggravate alcoholic liver injury. Our study helped us to better understand the sensitive role of IR on ALD and suggested that alcohol intake may be more harmful for people with IR.
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http://dx.doi.org/10.1016/j.lfs.2022.120681DOI Listing
August 2022

Snake Venom Hydrogels as a Rapid Hemostatic Agent for Uncontrolled Bleeding.

Adv Healthc Mater 2022 Jun 2:e2200574. Epub 2022 Jun 2.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD, 4072, Australia.

Uncontrolled bleeding from traumatic injury remains the leading cause of preventable death with loss of balance between blood clotting (coagulation) and blood clot breakdown (fibrinolysis). A major limitation of existing hemostatic agents is that they require a functioning clotting system to control the bleeding and are largely based on gauze delivery scaffolds. Herein, a novel rapid wound sealant, composed of two recombinant snake venom proteins, the procoagulant ecarin, to rapidly initiate blood clotting and the antifibrinolytic textilinin, to prevent blood clot breakdown within a synthetic thermoresponsive hydrogel scaffold is developed. In vitro, it is demonstrated that clotting is rapidly initiated with only nanomolar concentrations of venom protein and clot breakdown is effectively inhibited by textilinin. A stable clot is formed within 60 s compared to normal clot formation in 8 min. In vivo studies reveal that the snake venom hydrogel rapidly controls warfarin-induced bleeding, reducing the bleed volume from 48% to 12% and has demonstrated immune compatibility. A new class of hemostatic agents that achieve formation of rapid and stable blood clots even in the presence of blood thinners is demonstrated here.
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http://dx.doi.org/10.1002/adhm.202200574DOI Listing
June 2022

Fast, Sensitive, and Highly Selective Room-Temperature Hydrogen Sensing of Defect-Rich Orthorhombic NbO Nanobelts with an Abnormal -Type Sensor Response.

ACS Appl Mater Interfaces 2022 Jun 26;14(22):25937-25948. Epub 2022 May 26.

Hubei Engineering Research Center for Safety Detection and Control of Hydrogen Energy - Hubei Key Laboratory of Ferro- & Piezo-electric Materials and Devices, Faculty of Physics and Electronic Science, Hubei University, Wuhan 430062, P. R. China.

The research and development of low-power-consumption and room-temperature hydrogen sensors are of great significance for the safe application of hydrogen energy. Herein, orthorhombic NbO nanobelts are prepared through a combined procedure of hydrothermal, ion exchange, and annealing treatment in Ar. The topological transformation process results in the formation of abundant surface defects including chemical defects such as Nb, oxygen vacancies, and disordered microregions, which lead to the abnormal -type conducting and hydrogen sensing behavior. Moreover, the orthorhombic NbO nanobelts exhibit fast and sensitive room-temperature hydrogen sensing performance, which shows greater advancement than the monoclinic, tetragonal, and hexagonal NbO one-dimensional (1D) nanostructures. The response time and lowest limit of detection of the as-fabricated room-temperature sensor decrease to 28 s and 3.5 ppm, respectively. The sensor also exhibits a highly selective hydrogen response against CO, CH, ethanol, HS, and NH. The hydrogen response of the NbO nanobelts can be attributed to the redox reaction between hydrogen and preadsorbed oxygens. The defective surface structure and the prolonged dimension of the nanobelts give rise to the highly reactive surface and the suppression of the negative nanojunction effect, which greatly improves the sensing performance. The orthorhombic lattice structure can also promote gas adsorption and diffusion behavior due to its specific catalytic and pathway effect. The results of this work can be helpful for the rational design and defect engineering of the NbO-based 1D nanostructures for room-temperature hydrogen sensing applications.
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http://dx.doi.org/10.1021/acsami.2c05786DOI Listing
June 2022

Facile synthesis of multiphase cobalt-iron spinel with enriched oxygen vacancies as a bifunctional oxygen electrocatalyst.

Phys Chem Chem Phys 2022 Jun 8;24(22):13839-13847. Epub 2022 Jun 8.

National Engineering Research Centre of Industry Crystallization Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

The multiphase cobalt-iron spinel was firstly synthesized a facile cold plasma method and applied as a bifunctional electrocatalyst for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Compared with the single-phase obtained by the traditional calcination method, the CoFeO and CoO phase were obtained by the plasma method. The multivalence states of cobalt and iron facilitated electron transport in electrochemical reactions. The plasma sample had a small particle size (5 nm) due to the low operation temperature. Notably, electron impact produced more oxygen vacancies and a larger surface area on CoFeO, which increased the active sites and electronic conductivity. Electrochemical investigations indicated that the multiphase spinel obtained with a quasi-four-electron transfer process showed an onset potential of 0.76 V the RHE for the oxygen reduction reaction. In the oxygen evolution reaction, the potential of current density at 10 mA cm was 1.53 V RHE. As for the overall electrocatalytic activity, the multiphase spinel had a Δ (the difference between (OER) and (ORR)) of 0.89 V, exhibiting greater bifunctional activity than the other prepared catalysts.
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http://dx.doi.org/10.1039/d2cp00761dDOI Listing
June 2022

Label-free proteomics-based analysis of peripheral nerve injury induced by Japanese encephalitis virus.

J Proteomics 2022 Jul 20;264:104619. Epub 2022 May 20.

Neurology Center, Ningxia Medical University General Hospital, Yinchuan 750004, China; Diagnosis and Treatment Engineering Technology Research Center of Nervous System Diseases of Ningxia Hui Autonomous Region, Yinchuan 750004, China. Electronic address:

Japanese encephalitis (JE) is just an acute encephalitis syndrome contributed to Japanese encephalitis virus (JEV) infection. It the chief causes of viral encephalitis in Asia. In recent years, association of JEV infection with neurological problems such as Guillain-Barré syndrome(GBS) had reported. Nevertheless, its potential pathogenic mechanism has not previously been reported. Therefore, it is urgent to study the relationship between peripheral nerve injury (PNI) and JEV infection. Here, we use the liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique to make out the protein expression levels of mice sciatic nerve between JEV infection group and the sham group. In general, 4303 proteins were designated by MS, and 187 differentially expressed proteins(DEPs) were found. There were 105 proteins up-regulated in the injured sciatic nerve, and 82 proteins were down-regulated. Functional enrichment analysis of DEPs showed that the up-regulated proteins were mainly related to immune regulatory response, and down-regulated proteins were related to ribosomal structural components and translation. SIGNIFICANCE: The Japanese encephalitis virus, a member of the flavivirus, is a Mosquito borne virus. It leads to central nervous system injury by the immune response and inflammation in the brain. In addition, the virus also gave rise to PNI. It is a major public health problem in Asia. The diversity of clinical symptoms has brought serious challenges to the diagnosis and treatment of the disease. Label-Free Proteomics was undertaken to explore the potential mechanisms between JEV and peripheral nervous system in this study. It provided strong evidence that tissue damage is caused by the immune-mediated mechanisms rather than the virus, which offers a basis for the prevention of the disease and further looking for treatment targets.
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http://dx.doi.org/10.1016/j.jprot.2022.104619DOI Listing
July 2022

WZYH01 and WZYH02 Improve Salt Tolerance of Maize ( L.) in Saline Soil.

Front Plant Sci 2022 6;13:891372. Epub 2022 May 6.

State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan, China.

With the increasing shortage of land resources and people's attention to the ecological environment, the application of microbial fertilizer with natural soil microorganisms as the main component has attracted increasing attention in saline agriculture. In this study, two salt-tolerant strains, YL07 () and YL10 (), were isolated from maize ( L.) rhizosphere soil with a saturated conductivity (EC) of 6.13 dS/m and pH of 8.32 (Xinjiang, China). The effects of WZYH01 (YL07) and WZYH02 (YL10) on the growth and development of maize ( L.) under salt stress (EC = 5.9 dS/m) were further studied. The results showed that compared with uninoculation, inoculation with WZYH01 and WZYH02 significantly improved maize growth performance, biomass yield, and antioxidant levels under salt stress, and the effect of WZYH02 was more prominent than the effect of WZYH01. Moreover, inoculation with WZYH01 and WZYH02 protected maize from salt stress by regulating plant hormone [IAA and abscisic acid (ABA)] levels and increasing nutrient acquisition. In addition, the tested strains were most efficient for maize growth and health, increasing the content of K accompanied by an effective decrease in Na in maize tissues. The transcription levels of salt tolerance genes (, , , , and ) in inoculated maize were also dramatically higher than the transcription levels of the specified salt tolerance genes in uninoculated maize. In conclusion, WZYH01 and WZYH02 can alleviate the harmful effects of salt stress on crop growth, thereby promoting sustainable agricultural development.
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http://dx.doi.org/10.3389/fpls.2022.891372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121094PMC
May 2022

Real-time image-guided indocyanine green fluorescence dual-visualization technique to measure the intraoperative resection margin during thoracoscopic segmentectomy.

Asia Pac J Clin Oncol 2022 May 22. Epub 2022 May 22.

Department of Thoracic Surgery, Nanjing Chest Hospital, Nanjing, China.

Aims: The primary goal of thoracoscopic segmentectomy is the complete resection of early pulmonary carcinoma while sparing as much of the normal pulmonary parenchyma as possible, but an obvious trade-off exists between the pulmonary parenchymal preservation and an adequate resection margin. In this clinical trial, we explored a real-time image-guided indocyanine green (ICG) fluorescence dual-visualization technique to confirm the resection margin by improving the intraoperative localization of the pulmonary nodule and identification of the intersegmental boundary line (IBL).

Methods: This study was utilized in 35 patients with a screening-detected lung nodule <2 cm to complete thoracoscopic segmentectomy from December 2020 to June 2021. Computed tomography-guided localization of the pulmonary nodule with ICG solution was performed on the day of surgery. During the surgery, after dissecting the targeted pulmonary segmental arteries, ICG at 5 mg/body was injected into the systemic vein.

Results: We observed no toxicity. The dual-visualization technique was successfully implemented in all 35 patients to achieve a negative resection margin, which was more than 2 (mean 2.71 ± 0.59) cm, or the size of the tumor based on the final pathological examinations. No intraoperative complications occurred and only one patient had postoperative prolonged air leaks, which was ceased 8 days later after conservative management without reoperation.

Conclusions: This method is a safe and feasible alternative to ensure a negative resection margin without removing an unreasonable amount of pulmonary parenchyma during pulmonary segmentectomy. Future studies will be needed to compare this method to alternative techniques in a clinical trial.
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http://dx.doi.org/10.1111/ajco.13771DOI Listing
May 2022

The role of placebo response in the efficacy outcome assessment in viloxazine extended-release pivotal trials in paediatric subjects with attention-deficit/hyperactivity disorder.

Br J Clin Pharmacol 2022 May 19. Epub 2022 May 19.

Supernus Pharmaceuticals, Inc., Rockville, MD, USA.

Aims: Four Phase 3 studies evaluated efficacy and safety of viloxazine extended-release in the treatment of attention-deficit/hyperactivity disorder (ADHD). The primary efficacy objective-change from baseline in ADHD Rating Scale-5 (ADHD-RS-5) Total score at end of study (EOS)-was not met in one of the studies (812P304). A band-pass analysis was performed to evaluate the impact of placebo response on the results.

Methods: The distribution of placebo response at EOS of each trial was evaluated. The 2.5 and 97.5 percentiles of the distribution of ADHD-RS-5 Total score were used as boundaries for the band-pass analysis. An independent mixed model for repeated measures analysis was conducted for each trial using all eligible data (active and placebo) from the total and band-pass filtered populations.

Results: The 2.5 and 97.5 percentiles at EOS were 3.5 and 53.5, respectively. Application of the band-pass filter (filtering out all subjects [active, n = 305 (32.1%) and placebo, n = 134 (33.5%)] of clinical sites with placebo scores <3.5 or >53.5) revealed statistically significant improvement at the primary endpoint (600-mg/d viloxazine ER vs. placebo) in Study 812P304 (mean [confidence interval] = 4.9537 [0.5405-9.3669]), previously masked by a high placebo response (mean [confidence interval] = 3.5756 [-0.3332-7.4844]). The outcome of the analysis indicated that the impact of the band-pass adjustment is greater when placebo response is higher.

Conclusion: This analysis indicated that a higher placebo response in Study 812P304 confounded the assessment of treatment effect. Application of the band-pass methodology confirmed the positive results of the 3 prior studies and the signal detection confounder in the fourth study.
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http://dx.doi.org/10.1111/bcp.15412DOI Listing
May 2022

Physiological response of barley seedlings to salinity and artemisinin combined stresses under freeze-thaw environment.

Environ Sci Pollut Res Int 2022 May 19. Epub 2022 May 19.

College of Plant Science, Jilin University, Changchun, 130062, China.

In the Qinghai-Tibet Plateau, both the large daily temperature difference and soil salinization make plants susceptible to abiotic stresses such as freeze-thaw and salinity. Meanwhile, crops in this area can be affected by artemisinin, an antimalarial secondary metabolite produced in Artemisia. Under freeze-thaw and salinity stresses, artemisinin was induced as an allelopathy stress factor to explore the physiological response of highland barley, including the relative electrical conductivity (RC), soluble protein (SP) content, malondialdehyde (MDA) content, antioxidant enzyme activity, and water use efficiency (WUE). Compared with the control group, the contents of RC and MDA in seedling leaves under stress were significantly increased by 24.74-402.37% and 20.18-77.95%, indicating that cell membrane permeability was greatly damaged, and WUE was significantly decreased by 15.77-238.59%. The activity of enzymes increased under single stress and decreased under combined stress. Salinity, artemisinin, and freeze-thaw stress show a synergistic relationship; that is, compound stresses were more serious than single stress. In summary, the results of this study revealed the physiological and ecological responses of barley seedlings under different habitat stresses and the interactions among different stress factors.
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http://dx.doi.org/10.1007/s11356-022-20800-2DOI Listing
May 2022

Microscopic-Level Insights into the Mechanism of Enhanced NH Synthesis in Plasma-Enabled Cascade N Oxidation-Electroreduction System.

J Am Chem Soc 2022 Jun 19;144(23):10193-10200. Epub 2022 May 19.

State Key Laboratory of Fine Chemicals, Liaoning Key Lab for Energy Materials and Chemical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.

Integrated/cascade plasma-enabled N oxidation and electrocatalytic NO (where = 2, 3) reduction reaction (pNOR-eNORR) holds great promise for the renewable synthesis of ammonia (NH). However, the corresponding activated effects and process of plasma toward N and O molecules and the mechanism of eNORR to NH are unclear and need to be further uncovered, which largely limits the large-scale deployment of this process integration technology. Herein, we systematically investigate the plasma-enabled activation and recombination processes of N and O molecules, and more meaningfully, the mechanism of eNORR at a microscopic level is also decoupled using copper (Cu) nanoparticles as a representative electrocatalyst. The concentration of produced NO in the pNOR system is confirmed as a function of the length for spark discharge as well as the volumetric ratio for N and O feeding gas. The successive protonation process of NO and the key N-containing intermediates (e.g., -NH) of eNORR are detected with infrared spectroscopy. Besides, Raman spectroscopy further reveals the dynamic reconstruction process of Cu nanoparticles during the eNORR process. The Cu nanoparticle-driven pNOR-eNORR system can finally achieve a high NH yield rate of ∼40 nmol s cm and Faradaic efficiency of nearly 90%, overperforming the benchmarks reported in the literature. It is anticipated that this work will stimulate the practical development of the pNOR-eNORR system for the green electrosynthesis of NH directly from air and water under ambient conditions.
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http://dx.doi.org/10.1021/jacs.2c00089DOI Listing
June 2022

Spiritual care needs and their associated influencing factors among elderly patients with moderate-to-severe chronic heart failure in China: A cross-sectional study.

Palliat Support Care 2022 04;20(2):264-274

School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: The significance of spiritual care needs among chronic diseases patients has been emphasized across countries and cultures in many studies. However, there were few studies on spiritual care needs among elderly patients with moderate-to-severe chronic heart failure (CHF) in China.

Objective: To investigate spiritual care needs and associated influencing factors among elderly patients with moderate-to-severe CHF, and to examine the relationships among spiritual care needs, self-perceived burden, symptom management self-efficacy, and perceived social support.

Methods: A cross-sectional design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 474 elderly patients with moderate-to-severe CHF were selected from seven hospitals in Tianjin, China. The sociodemographic characteristics questionnaire, the Spiritual Needs Questionnaire Scale, the Self-Perceived Burden Scale, the Self-efficacy for Symptom Management Scale, and the Perceived Social Support Scale were used. Descriptive statistics, univariate, multiple linear regression, and Pearson's correlation analysis were used to analyze data.

Results: The total score of spiritual care needs among 474 elderly patients with moderate-to-severe CHF was 37.95 ± 14.71, which was moderate. Religious belief, educational background, self-perceived burden, symptom management self-efficacy, and perceived social support were the main factors affecting spiritual care needs, and spiritual care needs were negatively correlated with self-perceived burden (r = -0.637, p < 0.01) and positively correlated with symptom management self-efficacy (r = 0.802, p < 0.01) and social support (r = 0.717, p < 0.01).

Significance Of Results: The spiritual care needs of elderly patients with moderate-to-severe CHF were moderate, which were influenced by five factors. It is suggested that clinical nurses, families, and society should take targeted spiritual care measures to improve patients' symptom management self-efficacy and perceived social support from many aspects, and reduce self-perceived burden to meet their spiritual care needs and improve the quality and satisfaction of spiritual care in nursing practice.
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http://dx.doi.org/10.1017/S1478951521001279DOI Listing
April 2022

ATF4 Protects the Heart From Failure by Antagonizing Oxidative Stress.

Circ Res 2022 Jun 16;131(1):91-105. Epub 2022 May 16.

Division of Cardiology, Department of Internal Medicine (X.W., G.Z., S.D., E.L.N., C.L., Q.L., X.L., A.F., B.A.R., T.G.G., J.A.H., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.

Background: Cellular redox control is maintained by generation of reactive oxygen/nitrogen species balanced by activation of antioxidative pathways. Disruption of redox balance leads to oxidative stress, a central causative event in numerous diseases including heart failure. Redox control in the heart exposed to hemodynamic stress, however, remains to be fully elucidated.

Methods: Pressure overload was triggered by transverse aortic constriction in mice. Transcriptomic and metabolomic regulations were evaluated by RNA-sequencing and metabolomics, respectively. Stable isotope tracer labeling experiments were conducted to determine metabolic flux in vitro. Neonatal rat ventricular myocytes and H9c2 cells were used to examine molecular mechanisms.

Results: We show that production of cardiomyocyte NADPH, a key factor in redox regulation, is decreased in pressure overload-induced heart failure. As a consequence, the level of reduced glutathione is downregulated, a change associated with fibrosis and cardiomyopathy. We report that the pentose phosphate pathway and mitochondrial serine/glycine/folate metabolic signaling, 2 NADPH-generating pathways in the cytosol and mitochondria, respectively, are induced by transverse aortic constriction. We identify ATF4 (activating transcription factor 4) as an upstream transcription factor controlling the expression of multiple enzymes in these 2 pathways. Consistently, joint pathway analysis of transcriptomic and metabolomic data reveal that ATF4 preferably controls oxidative stress and redox-related pathways. Overexpression of ATF4 in neonatal rat ventricular myocytes increases NADPH-producing enzymes' whereas silencing of ATF4 decreases their expression. Further, stable isotope tracer experiments reveal that ATF4 overexpression augments metabolic flux within these 2 pathways. In vivo, cardiomyocyte-specific deletion of ATF4 exacerbates cardiomyopathy in the setting of transverse aortic constriction and accelerates heart failure development, attributable, at least in part, to an inability to increase the expression of NADPH-generating enzymes.

Conclusions: Our findings reveal that ATF4 plays a critical role in the heart under conditions of hemodynamic stress by governing both cytosolic and mitochondrial production of NADPH.
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http://dx.doi.org/10.1161/CIRCRESAHA.122.321050DOI Listing
June 2022

TLR2/TLR4-Enhanced TIPE2 Expression Is Involved in Post-Hemorrhagic Shock Mesenteric Lymph-Induced Activation of CD4+T Cells.

Front Immunol 2022 29;13:838618. Epub 2022 Apr 29.

Institute of Microcirculation, Hebei North University, Zhangjiakou, China.

Purpose: Post hemorrhagic shock mesenteric lymph (PHSML) return contributes to CD4 T cell dysfunction, which leads to immune dysfunction and uncontrolled inflammatory response. Tumor necrosis factor α induced protein 8 like-2 (TIPE2) is one of the essential proteins to maintain the immune homeostasis. This study investigated the role of TIPE2 in regulation of CD4 T lymphocyte function in interaction of PHSML and TLR2/TLR4.

Methods: The splenic CD4 T cells were isolated from various mice (WT, TLR2, TLR4) by immunomagnetic beads, and stimulated with PHSML, normal lymphatic fluid (NML), respectively. Application of TIPE2-carrying interfering fragments of lentivirus were transfected to WT, TLR4, and TLR2 CD4 T cells, respectively. After interference of TIPE2, they were stimulated with PHSML and NML for the examinations of TIPE2, TLR2, and TLR4 mRNA expressions, proliferation, activation molecules on surface, and cytokine secretion function.

Results: PHSML stimulation significantly upregulated TIPE2, TLR2, and TLR4 mRNA expressions, decreased proliferation, CD25 expression, and IFN-γ secretion, and increased the secretion ability of IL-4 in WT CD4 T cells. TIPE2 silencing enhanced proliferative capacity, upregulated CD25 expression, and increased IFNγ secretion in CD4 T cells. PHSML stimulated TLR2CD4 T or TLR4CD4 T cells of which TIPE2 were silenced. TLR2 or TLR4 knockout attenuated PHSML-induced CD4 T cells dysfunction; PHSML stimulation of silent TIPE2-expressing TLR2CD4 T or TLR4CD4 T revealed that the coexistence of low TIPE2 expression with lack of TLR2 or TLR4 eliminated this beneficial effect.

Conclusion: TIPE2 improves the PHSML-mediated CD4T cells dysfunction by regulating TLR2/TLR4 pathway, providing a new intervention target following hemorrhagic shock-induced immune dysfunction.
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http://dx.doi.org/10.3389/fimmu.2022.838618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101470PMC
April 2022

The Prognostic Nutritional Index May Predict Left Atrial Appendage Thrombus or Dense Spontaneous Echo Contrast in Patients With Atrial Fibrillation.

Front Cardiovasc Med 2022 29;9:860624. Epub 2022 Apr 29.

Department of Ultrasonography, Ningbo First Hospital, Ningbo, China.

Objectives: The prognostic nutritional index (PNI) is an independent predictor of adverse outcomes in patients with cardiovascular diseases. The presence of left atrial appendage thrombus (LAAT) or spontaneous echo contrast (SEC) is associated with ischemic stroke. The present study aimed to investigate the relationship between the PNI and LAAT/dense SEC in patients with non-valvular atrial fibrillation (AF).

Methods: In patients with non-valvular AF, we compared demographics, clinical characteristics, and prevalence of LAAT/dense SEC according to the levels of the PNI. The relationship between the PNI and LAAT/dense SEC was observed.

Results: A total of 406 patients with non-valvular AF were consecutively included from March 2015 to February 2019. Of the study population, 53 patients had LAAT/dense SEC. The percentages of LAAT/dense SEC were 20.4, 14.1, and 4.5% in subjects from the lowest to the highest tertile of the PNI, respectively. Multivariate logistic analysis demonstrated that the PNI was an independent predictor for LAAT/dense SEC (OR 0.89; 95% CI, 0.82-0.97; = 0.007). Receiver operating characteristic curve analysis revealed that the optimal cutoff value of the PNI for predicting LAAT/dense SEC was 48.0 (area under the curve: 0.68; 95% CI, 0.61-0.75; < 0.001). The sensitivity and specificity were 83.0 and 47.6%, respectively. The risk of LAAT/dense SEC in patients with a PNI ≤ 48.0 was 2.57-fold higher than that in those with a PNI > 48.0.

Conclusion: The PNI, calculated based on serum albumin and lymphocyte count, was inversely correlated with LAAT/dense SEC in patients with non-valvular AF. Therefore, it may be considered a predictor for LAAT/dense SEC.
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http://dx.doi.org/10.3389/fcvm.2022.860624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098831PMC
April 2022

Assessment of a full-scale solid-state anaerobic co-digestion: A multi-component substrate analysis by using ORWARE.

Waste Manag 2022 Jun 10;146:36-43. Epub 2022 May 10.

Department of Building Engineering, Energy Systems and Sustainability Science, University of Gävle, SE-801 76, Sweden.

Long-term sustainable biogas production requires different raw material alternatives, especially when reducing the most desirable organic substrate, food waste, which has been set as a goal in the 2030 Agenda. In Sweden, horse manure (HM) is generated in large quantities, and due to its physical and chemical characteristics, it has the potential to be used as a raw material to produce biogas through anaerobic digestion (AD). In order to investigate the challenges that HM digestion can impose in terms of methane yield and/or digestate quality, the modified ORganic WAste REsearch (ORWARE) AD model was applied. The aim was to study the effects of different substrates and combinations of these on the AD process during a full-scale solid-state (SS)-AD. In this sense, the model allows for the analysis of the digestion process of multicomponent substrates at the element level. The simulation results suggested that the replacement of green waste (GW) by HM with wood chips as bedding material gave the best improvement in terms of energy turnover; the liquid fraction of the digestate of this mixture of substrates presented the highest concentration in all the nutrients analyzed, specifically in total carbon-biological and phosphorus. The nutrient concentrations in the digestate from the aforementioned scenario are in line with the SPCR120 certification.
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http://dx.doi.org/10.1016/j.wasman.2022.04.042DOI Listing
June 2022

Fungal-sponge composite carriers coupled with denitrification and biomineralization bacteria to remove nitrate, calcium, and cadmium in a bioreactor.

Bioresour Technol 2022 Jul 9;355:127259. Epub 2022 May 9.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

The coexistence of nitrate (NO-N) and heavy metals in the aquatic environment causes harm to both the aquatic ecosystem and human health. Here, fungal-sponge composite carriers (FSC) were assembled and immobilized with strain WZ39 in a bioreactor to remove NO-N, Ca, and Cd. Stable bioreactor performance under heavy metal pressure was achieved. The highest removal efficiencies of NO-N, Ca, and Cd reached 100, 71.81, and 92.50%, respectively. Bacteria and precipitates were found in fungal mycelium and sponge. The precipitates composed of Ca(CaCd)(PO)(OH), CaCO, and CdCO. Fluorescence excitation-emission matrix (EEM) and flow cytometric (FCM) analysis indicated bacteria in FSC exhibited a strong metabolic activity and high percentage of intact cells under heavy metal stress. High-throughput sequencing results showed Pseudomonas sp. WZ39 played a major role in the bioreactor. The potential functions associated with metabolism, heavy metal transfer, and biofilm formation had high relative abundance in the bioreactor.
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http://dx.doi.org/10.1016/j.biortech.2022.127259DOI Listing
July 2022

Mechanically Promoted Synthesis of Polymer Organogels via Disulfide Bond Cross-Linking.

ACS Macro Lett 2021 07 14;10(7):799-804. Epub 2021 Jun 14.

Pritzker School of Molecular Engineering, University of Chicago, Chicago, Illinois 60637, United States.

Mechanically adaptive polymers could significantly improve the life-cycle of current materials. Piezo-polymerization is a novel approach that harnesses vibrational mechanical energy through piezoelectric nanoparticles to generate chemical promoters for linear polymerization and cross-linking reactions. However, the available piezo-polymerization systems rely on reactions forming irreversible covalent bonds. Dynamic covalent linkages could impart further adaptability to these polymeric systems. Here we show the first example of the piezoelectrochemical synthesis of disulfide bonds to form organogels from polymers with thiol side groups. We demonstrate that the reaction proceeds via piezo-oxidation of the thiol to disulfide in the presence of ZnO nanoparticles and iodide anions under mechanical agitation. We use mechanical energy in the form of ultrasound (40 kHz) and low frequency vibrations (2 kHz) to synthesize a variety of organogels from common synthetic polymers. Additionally, we show that the polymers in these gels can be chemically recycled with a reducing agent. Finally, we study the thermal and mechanical properties of the composites obtained after drying the gels. We believe this new system adds to the piezo-polymerization repertoire and serves as the basis to fabricate mechanically adaptive polymeric materials via dynamic covalent bonds.
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http://dx.doi.org/10.1021/acsmacrolett.1c00337DOI Listing
July 2021

Greater Similarity Between L1 and L2's Brain Network in Adults Than in Children.

Front Neurosci 2022 25;16:816729. Epub 2022 Apr 25.

CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

It has been documented that processing L2 and L1 engages a very similar brain network in bilingual adults. However, it is not known whether this similarity is evident in bilingual children as well or it develops with learning from children to adults. In the current study, we compared brain activation in Chinese-English bilingual children and adults during L1 and L2 processing. We found greater similarity between L1 and L2 in adults than in children, supporting the convergence hypothesis which argues that when the proficiency of L2 increases, the L2's brain network converges to the L1's brain network. We also found greater differences between adults and children in the brain for L2 processing than L1 processing, even though there were comparable increase in proficiency from children to adults in L1 and L2. It suggests an elongated developmental course for L2. This study provides important insights about developmental changes in the bilingual brain.
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http://dx.doi.org/10.3389/fnins.2022.816729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9084229PMC
April 2022

Denitrification strategy of Pantoea sp. MFG10 coupled with microbial dissimilatory manganese reduction: Deciphering the physiological response based on extracellular secretion.

Bioresour Technol 2022 Jul 8;355:127278. Epub 2022 May 8.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

In this study, the manganese (Mn) reduction-coupled denitrification strategy of dissimilatory Mn reducing bacteria was insightfully investigated. Different parameters (MnO level, pH, and temperature) were optimized by kinetic fitting to improve denitrification and Mn reduction effects. The 300 mg L MnO addition achieved 98.72% NO-N removal in 12 h, which was 54.62% higher than blank group without MnO. Scale-up studies showed that the metabolic activity of the bacteria was effectively enhanced by the addition of MnO. Besides the deepening of humification in the system, tryptophan-like protein and polysaccharide as potential electron donor precursors revealed remarkable contributions to the extracellular secretion-dependent denitrification process of DMRB. The effect of EPS on Mn reduction depends mainly on the capture of MnO by the LB-EPS layer versus its dissolution in the TB-EPS layer. Ultimately, the EPS possess a dual effect of accelerated denitrification and Mn reduction efficiency due to the enhanced EET process.
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http://dx.doi.org/10.1016/j.biortech.2022.127278DOI Listing
July 2022

Fragile X Mental Retardation Protein Mediates the Effects of Androgen on Hippocampal PSD95 Expression and Dendritic Spines Density/Morphology and Autism-Like Behaviors Through miR-125a.

Front Cell Neurosci 2022 22;16:872347. Epub 2022 Apr 22.

Department of Anatomy, Hebei Medical University, Shijiazhuang, China.

Dysregulated synaptic plasticity is a key feature of neurodevelopmental disorders, including autism. This study investigated whether Fragile X mental retardation protein (FMRP), a selective RNA-binding protein that regulates synaptic protein expression by interacting with miRNAs, mediates the effects of androgens that play an important role in regulating the synaptic plasticity in the hippocampus. Experiments using mouse hippocampal neuron HT22 cells demonstrated that dihydrotestosterone (DHT) increased the expression of postsynaptic density protein 95 (PSD95) by inhibiting FMRP expression. Administration of miR-125a inhibitor upregulated the PSD95 expression and significantly increased the DHT-induced upregulation of PSD95. FMRP knockdown in HT22 cells reduced the expression of miR-125a. Moreover, miR-125a inhibitor upregulated the PSD95 expression in the DHT-treated HT22 cells with FMRP knockdown. Subsequently, the effects of androgen-mediated FMRP in regulating neural behaviors and PSD95 expression and dendritic spines density/morphology were investigated using knockout (KO) and wild-type littermate (WT) mice. The castration of WT mice reduced the androgen levels, aggravated anxiety and depression, and impaired learning and memory and sociability of mice. DHT supplementation post-castration reversed the alterations in density and maturity of dendritic spines of hippocampal neurons and behavioral disorders in WT mice; however, it did not reveal such effects in KO mice. Further, immunohistochemical staining and western blotting analyses after knocking down miR-125a revealed similar effects of castration and post-castration DHT supplementation on PSD95 protein expression. These findings clarified that FMRP mediated the effects of DHT through miR-125a in regulating the expression of hippocampal synaptic protein PSD95. This study provides evidence for the neuroprotective mechanism of androgen in PSD95 expression and dendritic spines density/morphology and suggests that treatment interventions with androgen could be helpful for the management of synaptic plasticity disorders.
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http://dx.doi.org/10.3389/fncel.2022.872347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074813PMC
April 2022
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