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1.
PLoS Biol ; 20(12): e3001730, 2022 12.
Article in English | MEDLINE | ID: mdl-36469518

ABSTRACT

The brain as a central regulator of stress integration determines what is threatening, stores memories, and regulates physiological adaptations across the aging trajectory. While sleep homeostasis seems to be linked to brain resilience, how age-associated changes intersect to adapt brain resilience to life history remains enigmatic. We here provide evidence that a brain-wide form of presynaptic active zone plasticity ("PreScale"), characterized by increases of active zone scaffold proteins and synaptic vesicle release factors, integrates resilience by coupling sleep, longevity, and memory during early aging of Drosophila. PreScale increased over the brain until mid-age, to then decreased again, and promoted the age-typical adaption of sleep patterns as well as extended longevity, while at the same time it reduced the ability of forming new memories. Genetic induction of PreScale also mimicked early aging-associated adaption of sleep patterns and the neuronal activity/excitability of sleep control neurons. Spermidine supplementation, previously shown to suppress early aging-associated PreScale, also attenuated the age-typical sleep pattern changes. Pharmacological induction of sleep for 2 days in mid-age flies also reset PreScale, restored memory formation, and rejuvenated sleep patterns. Our data suggest that early along the aging trajectory, PreScale acts as an acute, brain-wide form of presynaptic plasticity to steer trade-offs between longevity, sleep, and memory formation in a still plastic phase of early brain aging.


Subject(s)
Drosophila melanogaster , Drosophila , Animals , Drosophila melanogaster/genetics , Synapses/physiology , Aging/physiology , Brain/physiology , Neuronal Plasticity/physiology
2.
Small ; 20(24): e2311764, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38506607

ABSTRACT

The development of novel method for drug-resistant bacteria detection is imperative. A simultaneous dual-gene Test of methicillin-resistant Staphylococcus aureus (MRSA) is developed using an Argonaute-centered portable biosensor (STAR). This is the first report concerning Argonaute-based pathogenic bacteria detection. Simply, the species-specific mecA and nuc gene are isothermally amplified using loop-mediated isothermal amplification (LAMP) technique, followed by Argonaute-based detection enabled by its programmable, guided, sequence-specific recognition and cleavage. With the strategy, the targeted nucleic acid signals gene are dexterously converted into fluorescent signals. STAR is capable of detecting the nuc gene and mecA gene simultaneously in a single reaction. The limit of detection is 10 CFU/mL with a dynamic range from 10 to 107 CFU/mL. The sample-to-result time is <65 min. This method is successfully adapted to detect clinical samples, contaminated foods, and MRSA-infected animals. This work broadens the reach of Argonaute-based biosensing and presents a novel bacterial point-of-need (PON) detection platform.


Subject(s)
Biosensing Techniques , Methicillin-Resistant Staphylococcus aureus , Nucleic Acid Amplification Techniques , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Biosensing Techniques/methods , Nucleic Acid Amplification Techniques/methods , Argonaute Proteins/metabolism , Argonaute Proteins/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Penicillin-Binding Proteins/genetics , Animals , Micrococcal Nuclease/metabolism , Micrococcal Nuclease/genetics
3.
Nature ; 560(7718): 336-339, 2018 08.
Article in English | MEDLINE | ID: mdl-30038286

ABSTRACT

A ferroelectric is a material with a polar structure whose polarity can be reversed (switched) by applying an electric field1,2. In metals, itinerant electrons screen electrostatic forces between ions, which explains in part why polar metals are very rare3-7. Screening also excludes external electric fields, apparently ruling out the possibility of ferroelectric switching. However, in principle, a thin enough polar metal could be sufficiently penetrated by an electric field to have its polarity switched. Here we show that the topological semimetal WTe2 provides an embodiment of this principle. Although monolayer WTe2 is centro-symmetric and thus non-polar, the stacked bulk structure is polar. We find that two- or three-layer WTe2 exhibits spontaneous out-of-plane electric polarization that can be switched using gate electrodes. We directly detect and quantify the polarization using graphene as an electric-field sensor8. Moreover, the polarization states can be differentiated by conductivity and the carrier density can be varied to modify the properties. The temperature at which polarization vanishes is above 350 kelvin, and even when WTe2 is sandwiched between graphene layers it retains its switching capability at room temperature, demonstrating a robustness suitable for applications in combination with other two-dimensional materials9-12.

4.
J Toxicol Environ Health A ; 87(10): 428-435, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38551404

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease associated with long non-coding RNAs and DNA methylation; however, the mechanisms underlying the role of lncRNA small nucleolar RNA host gene 1 (lncRNA SNHG1) and subsequent involvement of DNA methylation in AD development are not known. The aim of this study was to examine the regulatory mechanisms attributed to lncRNA SNHG1 gene utilizing 2 strains of senescence-accelerated mouse prone 8 (SAMP8) model of AD and compared to senescence-accelerated mouse resistant (SAMR) considered a control. Both strains of the mouse were transfected with either blank virus, psLenti-U6-SNHG1(low gene expression) virus, and psLenti-pA-SNHG1(gene overexpression) virus via a single injection into the brains for 2 weeks. At 2 weeks mice were subjected to a Morris water maze to determine any behavioral effects followed by sacrifice to extract hippocampal tissue for Western blotting to measure protein expression of p-tau, DNMT1, DNMT3A, DNMT3B, TET1, and p-Akt. No marked alterations were noted in any parameters following blank virus transfection. In SAMP8 mice, a significant decrease was noted in protein expression of DNMT1, DNMT3A, DNMT3B, and p-Akt associated with rise in p-tau and TET1. Transfection with ps-Lenti-U6-SNHG1 alone in SAMR1 mice resulted in a significant rise in DNMTs and p-Akt and a fall in p-tau and TET1. Transfection of SAMP8 with ps-Lenti-U6-SNHG1 blocked effects on overexpression noted in this mouse strain. However, knockdown of lncRNA SNHG1 yielded the opposite results as found in SAMR1 mice. In conclusion, the knockdown of lncRNA SNHG1 enhanced DNA methylation through the PI3K/Akt signaling pathway, thereby reducing the phosphorylation levels of tau in SAMP8 AD model mice with ameliorating brain damage attributed to p-tau accumulation with consequent neuroprotection.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , RNA, Long Noncoding , Mice , Animals , Alzheimer Disease/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , DNA Methylation , Proto-Oncogene Proteins c-akt/metabolism , Neurodegenerative Diseases/genetics , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism
5.
J Toxicol Environ Health A ; 87(10): 421-427, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38551405

ABSTRACT

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.


Subject(s)
Dementia, Vascular , Lignans , Neuroblastoma , Polycyclic Compounds , Rats , Humans , Animals , Dementia, Vascular/drug therapy , Dementia, Vascular/etiology , Dementia, Vascular/metabolism , Maze Learning/physiology , Hypoxia , Cognition , Hippocampus , Oxygen/pharmacology , Cyclooctanes
6.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Article in English | MEDLINE | ID: mdl-34385302

ABSTRACT

Regulation of the nucleocytoplasmic trafficking of signaling components, especially transcription factors, is a key step of signal transduction in response to extracellular stimuli. In the brassinosteroid (BR) signal transduction pathway, transcription factors from the BRASSINAZOLE RESISTANT1 (BZR1) family are essential in mediating BR-regulated gene expression. The subcellular localization and transcriptional activity of BZR1 are tightly regulated by reversible protein phosphorylation; however, the underlying mechanism is not well understood. Here, we provide evidence that both BZR1 phosphorylation and dephosphorylation occur in the nucleus and that BR-regulated nuclear localization of BZR1 is independent from its interaction with, or dephosphorylation by, protein phosphatase 2A. Using a photoconvertible fluorescent protein, Kaede, as a living tag to distinguish newly synthesized BZR1 from existing BZR1, we demonstrated that BR treatment recruits cytosolic BZR1 to the nucleus, which could explain the fast responses of plants to BR. Additionally, we obtained evidence for two types of protein turnover mechanisms that regulate BZR1 abundance in plant cells: a BR- and 26S proteosome-independent constitutive degradation mechanism and a BR-activated 26S proteosome-dependent proteolytic mechanism. Finally, treating plant cells with inhibitors of 26S proteosome induces the nuclear localization and dephosphorylation of BZR1, even in the absence of BR signaling. Based on these results, we propose a model to explain how BR signaling regulates the nucleocytoplasmic trafficking and reversible phosphorylation of BZR1.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , DNA-Binding Proteins/metabolism , Gene Expression Regulation, Plant/physiology , Active Transport, Cell Nucleus , Arabidopsis/genetics , Arabidopsis Proteins/genetics , DNA-Binding Proteins/genetics , Mutation , Plants, Genetically Modified , Seedlings
7.
Int J Biometeorol ; 68(2): 393-400, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38110789

ABSTRACT

BACKGROUND: Low air quality related to ambient air pollution is the largest environmental risk to health worldwide. Interactions between air pollution emissions may affect associations between air pollution exposure and chronic diseases. Therefore, this study aimed to quantify interactions among air pollution emissions and assess their effects on the association between air pollution and diabetes. METHODS: After constructing long-term emission networks for six air pollutants based on data collected from routine monitoring stations in Northeast China, a mutual information network was used to quantify interactions among air pollution emissions. Multiple linear regression analysis was then used to explore the influence of emission interactions on the association between air pollution exposure and the prevalence of diabetes based on data reported from the Northeast Natural Cohort Study in China. RESULTS: Complex network analysis detected three major emission sources in Northeast China located in Shenyang and Changchun. The effects of particulate matter (PM2.5 and PM10) and ground-level ozone (O3) emissions were limited to certain communities but could spread to other communities through emissions in Inner Mongolia. Emissions of sulfur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO) significantly influenced other communities. These results indicated that air pollutants in different geographic areas can interact directly or indirectly. Adjusting for interactions between emissions changed associations between air pollution emissions and diabetes prevalence, especially for PM2.5, NO2, and CO. CONCLUSIONS: Complex network analysis is suitable for quantifying interactions among air pollution emissions and suggests that the effects of PM2.5 and NO2 emissions on health outcomes may have been overestimated in previous population studies while those of CO may have been underestimated. Further studies examining associations between air pollution and chronic diseases should consider controlling for the effects of interactions among pollution emissions.


Subject(s)
Air Pollutants , Air Pollution , Diabetes Mellitus , Ozone , Humans , Air Pollutants/analysis , Nitrogen Dioxide/analysis , Cohort Studies , Prevalence , Air Pollution/analysis , Particulate Matter/analysis , Ozone/analysis , Sulfur Dioxide/analysis , China/epidemiology , Diabetes Mellitus/epidemiology , Chronic Disease , Environmental Exposure/analysis
8.
J Wound Ostomy Continence Nurs ; 51(2): 111-116, 2024.
Article in English | MEDLINE | ID: mdl-38527319

ABSTRACT

PURPOSE: The primary aims of this study were to evaluate the prevalence of wound-related pain (WRP) in patients with chronic wounds and assess the use of pain relief measures. DESIGN: A cross-sectional study. SUBJECTS AND SETTING: A convenience sample of patients with chronic wounds was recruited from outpatient clinics of 12 hospitals covering 7 of 13 cities in the Jiangsu province located in eastern China from July 10 to August 25, 2020. The sample comprised 451 respondents, and their mean age was 54.85 (SD 19.16) years; 56.1% (253/451) patients were male. METHODS: An investigator-designed questionnaire was used to collect pain-related information from patients. The questionnaire consisted of 4 parts: (1) basic demographic and clinical information (patient and wound characteristics); (2) wound baseline pain; (3) wound-related procedural pain and pain relief method; and (4) the effect of WRP on the patient. Pain was assessed using the Numerical Rating Scale (NRS) scored from 0 (no pain) to 10 (worst pain). Severity of pain was based on NRS scores' classification as mild (1-3), moderate (4-6), and severe (7-10). The survey was conducted from July 10 to August 25, 2020. Participants were instructed on use of the NRS and then completed the questionnaire following dressing change independently. RESULTS: The 3 most common types of chronic wounds were traumatic ulcers, surgical wounds, and venous leg ulcers. The 3 most prevalent locations were lower limbs, feet, and thorax/abdomen. Of all patients, 62.5% (282/451) and 93.8% (423/451) patients experienced wound baseline pain and wound-related procedural pain, respectively. The mean score of wound baseline pain was 3.76 (SD 1.60) indicating moderate pain. During wound management, the highest pain score was 6.45 (SD 2.75) indicating severe pain; the most severe pain scores were associated with debridement. The use of drugs to relieve wound pain was low, while the use of nondrug-based analgesia was relatively high. Because of WRP, patients with chronic wounds feared dressing changes, hesitated to move, and showed a decline in sleep quality. CONCLUSIONS: Wound baseline pain and wound-related procedural pain were very common in patients with chronic wounds. In the future, targeted intervention plans should be developed by combining drug-based and nondrug-based analgesia according to pain severity.


Subject(s)
Pain, Procedural , Varicose Ulcer , Humans , Male , Middle Aged , Female , Cross-Sectional Studies , Pain , Surveys and Questionnaires , Surgical Wound Infection
9.
J Am Chem Soc ; 145(50): 27900-27910, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-38078405

ABSTRACT

The fabrication of formamidinium lead iodide (FAPbI3) perovskite solar cells (PSCs) involves the addition of methylammonium chloride (MACl) to promote low-temperature α-phase formation and grain growth. However, as the added MACl deprotonates and volatilizes into methylamine (MA0) and HCl for removal, MA0 can chemically interact with formamidinium (FA+), forming methyl formamidinium (MFA+) as a byproduct. Despite its significance, the chemical interactions among FAPbI3 perovskites, MACl additives, and their byproducts remain poorly understood. Our findings reveal that the FA+ and MA0 reaction primarily yields a mixture of cis/trans-N-methyl formamidinium iodide (MFAI) isomers, with cis-MFAI prevailing as the dominant species. Moreover, MFAI subsequently reacts with PbI2 to yield fully formed cis-MFAPbI3 2H-phase perovskite. We elucidated the effects of MFAI on the crystal growth, phase stability, and band gap of formamidine-based perovskites through the growth of single crystals. This research offers valuable insights into the role of these byproducts in influencing the efficiency and long-term stability of future PSCs.

10.
Magn Reson Med ; 89(4): 1506-1513, 2023 04.
Article in English | MEDLINE | ID: mdl-36426774

ABSTRACT

PURPOSE: MRI studies in human subjects often require multiple scanning sessions/visits. Changes in a subject's head position across sessions result in different alignment between brain tissues and the magnetic field which leads to changes in magnetic susceptibility. These changes can have considerable impacts on acquired signals. Head ALignment Optimization (HALO), a software tool was developed by the authors for active head alignment between sessions. METHODS: HALO provides real-time visual feedback of a subject's current head position relative to the position in a previous session. The tool was evaluated in a pilot sample of seven healthy human subjects. RESULTS: HALO was shown to enable subjects to actively align their head positions to the desired position of their initial sessions. The subjects were able to improve their head alignment significantly using HALO and achieved good alignment with their first session meeting stringent criteria similar to that used for within-run head motion (less than 2 mm translation or 2 degrees rotation in any direction from the desired position). Moreover, we found a negative correlation between the post-alignment rotation and similarity in inter-session BOLD patterns around the air-tissue interface near sinus which further highlighted the impact of tissue-field alignment on BOLD data quality. CONCLUSION: Utilization of HALO in longitudinal studies may help to improve data quality by ensuring the consistency of susceptibility gradients in brain tissues across sessions. HALO has been made publicly available.


Subject(s)
Magnetic Resonance Imaging , Software , Humans , Rotation , Longitudinal Studies
11.
Opt Express ; 31(20): 31796-31805, 2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37858996

ABSTRACT

We propose an efficient and polarization-insensitive edge coupler (EC) constructed principally with two cascaded vertical waveguide tapers. The proposed edge coupler only requires ordinary 365 nm (i-line) ultraviolet source for lithography process. We experimentally demonstrate the proposed EC on two kinds of photonic integrated circuit (PIC) platforms: silicon nitride (Si3N4) and lithium niobate thin film. Both achieve polarization-insensitive fiber chip coupling efficiency of >70% in the C-band. Our proposed EC have the advantages of efficient, cost-saving, and easy to implement and could serve as an effective solution to facilitate low-loss chip-fiber coupling.

12.
Opt Express ; 31(19): 30658-30668, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37710605

ABSTRACT

We propose an electro-optic tunable optical filter based on sidewall long period waveguide grating (LPWG) in lithium niobate on insolator (LNOI). The operation of our proposed filter is based on the mode coupling, filtering, and absorption achieved, respectively, with two corrugated sidewall LPWGs, a tapered waveguide, and two metal ribbons. Our typical fabricated devices achieved a 16.32-dB rejection band and an EO tuning efficiency of ∼0.344 nm/V. Our proposed LPWG and filter are compact and could be integrated with other LNOI waveguide devices to realize more sophisticated functions for on-chip optical signal processing.

13.
Crit Rev Food Sci Nutr ; : 1-22, 2023 Sep 10.
Article in English | MEDLINE | ID: mdl-37691410

ABSTRACT

Food safety problems have become one of the most important public health issues worldwide. Therefore, the development of rapid, effective and robust detection is of great importance. Amongst a range of methods, nucleic acid isothermal amplification (NAIA) plays a great role in food safety detection. However, the widespread application remains limited due to a few shortcomings. CRISPR/Cas system has emerged as a powerful tool in nucleic acid detection, which could be readily integrated with NAIA to improve the detection sensitivity, specificity, adaptability versatility and dependability. However, currently there was a lack of a comprehensive summary regarding the integration of NAIA and CRISPR/Cas in the field of food safety detection. In this review, the recent advances in food safety detection based on CRISPR/Cas-integrated NAIA were comprehensively reviewed. To begin with, the development of NAIA was summarized. Then, the types and working principles of CRISPR/Cas were introduced. The applications of the integration of NAIA and CRISPR/Cas for food safety were mainly introduced and objectively discussed. Lastly, current challenges and future opportunities were proposed. In summary, this technology is expected to become an important approach for food safety detection, leading to a safer and more reliable food industry.

14.
Proc Natl Acad Sci U S A ; 117(35): 21766-21774, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32817516

ABSTRACT

Leaf architecture directly determines canopy structure, and thus, grain yield in crops. Leaf droopiness is an agronomic trait primarily affecting the cereal leaf architecture but the genetic basis and underlying molecular mechanism of this trait remain unclear. Here, we report that DROOPY LEAF1 (DPY1), an LRR receptor-like kinase, plays a crucial role in determining leaf droopiness by controlling the brassinosteroid (BR) signaling output in Setaria, an emerging model for Panicoideae grasses. Loss-of-function mutation in DPY1 led to malformation of vascular sclerenchyma and low lignin content in leaves, and thus, an extremely droopy leaf phenotype, consistent with its preferential expression in leaf vascular tissues. DPY1 interacts with and competes for SiBAK1 and as a result, causes a sequential reduction in SiBRI1-SiBAK1 interaction, SiBRI1 phosphorylation, and downstream BR signaling. Conversely, DPY1 accumulation and affinity of the DPY1-SiBAK1 interaction are enhanced under BR treatment, thus preventing SiBRI1 from overactivation. As such, those findings reveal a negative feedback mechanism that represses leaf droopiness by preventing an overresponse of early BR signaling to excess BRs. Notably, plants overexpressing DPY1 have more upright leaves, thicker stems, and bigger panicles, suggesting potential utilization for yield improvement. The maize ortholog of DPY1 rescues the droopy leaves in dpy1, suggesting its conserved function in Panicoideae. Together, our study provides insights into how BR signaling is scrutinized by DPY1 to ensure the upward leaf architecture.


Subject(s)
Brassinosteroids/metabolism , Plant Leaves/metabolism , Setaria Plant/genetics , Gene Expression Regulation, Plant/genetics , Mutation , Phenotype , Phosphorylation , Plant Leaves/genetics , Plant Leaves/growth & development , Plant Proteins/genetics , Plants, Genetically Modified/metabolism , Poaceae/genetics , Poaceae/metabolism , Setaria Plant/metabolism , Signal Transduction/physiology , Transcription Factors/metabolism
15.
Curr Psychol ; 42(11): 8897-8918, 2023.
Article in English | MEDLINE | ID: mdl-34400856

ABSTRACT

Motivated from the shortage of the existing research studies on impacts of dangerously contagious diseases on firms' financial performance, this study sheds light on the impacts of Coronavirus (Covid-19) outbreak on financial performance upon on the quarterly data of 126 Chinese listed firms across 16 industries. Overall, the Covid-19 outbreak reduced Chinese listed firms' financial performance proxied by the revenue growth rate, ROA, ROE, and asset turnover. This outbreak's negative effects on Chinese firms' profitability were much smaller than that on their revenue growth rates. While this outbreak's negative effects on financial performance of Chinese listed firms were bigger for those that were seriously affected by this pandemic like airlines, travel, and entertainment (ATE), this pandemic's effects were positive for the medicine industry. In the meanwhile, Chinese listed firms that located in high-risk regions suffered a bigger financial loss during the outbreak, and especially there was a strong Hubei effect. The corporate culture and CSR moderated the inverse relationship between this outbreak and Chinese firms' financial performance. Findings of this study contribute to enrich the existing literature on impacts of the Covid-19 outbreak on firms' financial performance worldwide and suggest helpful practical and theoretical implications.

16.
Lab Invest ; 102(6): 613-620, 2022 06.
Article in English | MEDLINE | ID: mdl-35042950

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common primary liver malignancies and is the third leading cause of tumor-related mortality worldwide. Despite advances in HCC treatment, diagnosis at the later stages, and the complex mechanisms relating to the cause and pathogenesis, results in less than 40% of HCC patients being eligible for potential therapy. Prolonged inflammation and resulting immunosuppression are major hallmarks of HCC; however, the mechanisms responsible for these processes have not been clearly elucidated. In this study, we identified SOCS-7, an inhibitor of cytokine signaling, as a novel regulator of immunosuppression in HCC. We found that SOCS-7 mediated E3 ubiquitin ligase activity on a signaling adaptor molecule, Shc1, in Huh-7 cells. Overexpression of SOCS-7 reduced the induction of immunosuppressive factors, TGF-ß, Versican, and Arginase-1, and further reduced STAT3 activation. Furthermore, using an in vivo tumor model, we confirmed that SOCS-7 negatively regulates immunosuppression and inhibits tumor growth by targeting Shc1 degradation. Together, our study identified SOCS-7 as a possible therapeutic target to reverse immunosuppression in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Src Homology 2 Domain-Containing, Transforming Protein 1 , Suppressor of Cytokine Signaling Proteins , Carcinoma, Hepatocellular/pathology , Humans , Immunosuppression Therapy , Liver Neoplasms/pathology , Signal Transduction , Src Homology 2 Domain-Containing, Transforming Protein 1/genetics , Src Homology 2 Domain-Containing, Transforming Protein 1/metabolism , Suppressor of Cytokine Signaling Proteins/genetics , Suppressor of Cytokine Signaling Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism
17.
Metab Eng ; 69: 188-197, 2022 01.
Article in English | MEDLINE | ID: mdl-34890798

ABSTRACT

Phenazines (Phzs), a family of chemicals with a phenazine backbone, are secondary metabolites with diverse properties such as antibacterial, anti-fungal, or anticancer activity. The core derivatives of phenazine, phenazine-1-carboxylic acid (PCA) and phenazine-1,6-dicarboxylic acid (PDC), are themselves precursors for various other derivatives. Recent advances in genome mining tools have enabled researchers to identify many biosynthetic gene clusters (BGCs) that might produce novel Phzs. To characterize the function of these BGCs efficiently, we performed modular construct assembly and subsequent multi-chassis heterologous expression using chassis-independent recombinase-assisted genome engineering (CRAGE). CRAGE allowed rapid integration of a PCA BGC into 23 diverse γ-proteobacteria species and allowed us to identify top PCA producers. We then used the top five chassis hosts to express four partially refactored PDC BGCs. A few of these platforms produced high levels of PDC. Specifically, Xenorhabdus doucetiae and Pseudomonas simiae produced PDC at a titer of 293 mg/L and 373 mg/L, respectively, in minimal media. These titers are significantly higher than those previously reported. Furthermore, selectivity toward PDC production over PCA production was improved by up to 9-fold. The results show that these strains are promising chassis for production of PCA, PDC, and their derivatives, as well as for function characterization of Phz BGCs identified via bioinformatics mining.


Subject(s)
Phenazines , Recombinases , Multigene Family , Phenazines/metabolism , Recombinases/genetics
18.
Microb Pathog ; 166: 105510, 2022 May.
Article in English | MEDLINE | ID: mdl-35421555

ABSTRACT

Tilapia lake virus disease (TiLVD) caused by Tilapia lake virus (TiLV) is a great threat to the global tilapia culture industry. Effective prevention and control strategies have not been developed due to limited basic research of pathogenesis of TiLVD. Cell lines from different fish species have been found to be permissive to TiLV infection. In the current study, we comprehensively analyzed TiLV susceptibilities to 10 permanent growing fish cell lines. We found that the highest viral titers were generated onto TiB cells originated from the tilapia species Oreochromis mossambicus, MSF from the largemouth bass Micropterus salmoides, CAMK from the hybrid snakehead Channa argus × Channa maculata and SS derived from the perch species Siniperca chuatsi. Viral copy numbers from these four cell lines ranged from 4 × 107 copies/µL to 4.6 × 108 copies/µL. Confocal immunofluorescent microscopy also indicated that all 10 cell lines can support varying degrees of viral infection and replication. TiLV particles can be observed in cells from randomly selected three fish species using electron microscope. This study will assist in research and development of prevention and control of TiLVD.


Subject(s)
Fish Diseases , RNA Viruses , Tilapia , Viruses , Animals , Cell Line , DNA Viruses , Disease Susceptibility
19.
Int J Neuropsychopharmacol ; 25(10): 807-817, 2022 10 25.
Article in English | MEDLINE | ID: mdl-35723242

ABSTRACT

BACKGROUND: The hypothalamic neuropeptide oxytocin (OXT) may exert anxiolytic and stress-reducing actions via modulatory effects on amygdala circuits. Animal models and initial findings in humans suggest that some of these effects are mediated by interactions with other neurotransmitter systems, in particular the serotonin (5-HT) system. Against this background, the present pharmacological resting-state functional magnetic resonance imaging study aimed to determine whether effects of OXT on stress-associated amygdala intrinsic networks are mediated by 5-HT. METHODS: We employed a randomized, placebo-controlled, double-blind parallel-group, pharmacological functional magnetic resonance imaging resting-state experiment with 4 treatment groups in n = 112 healthy male participants. Participants underwent a transient decrease in 5-HT signaling via acute tryptophan depletion (ATD) or a corresponding placebo-control protocol before the administration of intranasal OXT (24 IU) or placebo intranasal spray. RESULTS: OXT and 5-HT modulation exerted interactive effects on the coupling of the left amygdala with the ipsilateral hippocampus and adjacent midbrain. OXT increased intrinsic coupling in this pathway, whereas this effect of OXT was significantly attenuated during transiently decreased central serotonergic signaling induced via acute tryptophan depletion. In the absence of OXT or 5-HT modulation, this pathway showed a trend for an association with self-reported stress perception in everyday life. No interactive effects were observed for the right amygdala. CONCLUSIONS: Together, the findings provide the first evidence, to our knowledge, that the effects of OXT on stress-associated amygdala-hippocampal-midbrain pathways are critically mediated by the 5-HT system in humans.


Subject(s)
Anti-Anxiety Agents , Oxytocin , Humans , Male , Amygdala , Anti-Anxiety Agents/pharmacology , Hippocampus , Neurotransmitter Agents/pharmacology , Oxytocin/pharmacology , Serotonin , Tryptophan , Double-Blind Method
20.
Chemistry ; 28(16): e202104514, 2022 Mar 16.
Article in English | MEDLINE | ID: mdl-35118722

ABSTRACT

Exploring new catalytic strategies for achieving efficient CO2 hydrogenation under mild conditions is of great significance for environmental remediation. Herein, a composite photocatalyst Zr-based MOF encapsulated plasmonic AuPt alloy nanoparticles (AuPt@UiO-66-NH2 ) was successfully constructed for the efficient photothermal catalysis of CO2 hydrogenation. Under light irradiation at 150 °C, AuPt@UiO-66-NH2 achieved a CO production rate of 1451 µmol gmetal -1 h-1 with 91 % selectivity, which far exceeded those obtained by Au@Pt@UiO-66-NH2 with Pt shell on Au (599 µmol gmetal -1 h-1 ) and Au@UiO-66-NH2 (218 µmol gmetal -1 h-1 ). The outstanding performances of AuPt@UiO-66-NH2 were attributed to the synergetic effect originating from the plasmonic metal Au, doped active metal Pt, and encapsulation structure of UiO-66-NH2 shell. This work provides a new way for photothermal catalysis of CO2 and a reference for the design of high-performance plasmonic catalysts.

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