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1.
Nat Commun ; 15(1): 6977, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143099

ABSTRACT

Materials demonstrating positive thermal expansion (PTE) or negative thermal expansion (NTE) are quite common, whereas those exhibiting zero thermal expansion (ZTE) are notably scarce. In this work, we identify the mechanical descriptors, namely in-plane tensile stiffness and out-of-plane bending stiffness, that can effectively classify PTE and NTE 2D crystals. By utilizing high throughput calculations and the state-of-the-art symbolic regression method, these descriptors aid in the discovery of ZTE or 2D Invar monolayers with the linear thermal expansion coefficient (LTEC) within  ±2 × 10-6 K-1 in the middle range of temperatures. Additionally, the descriptors assist the discovery of large PTE and NTE 2D monolayers with the LTEC larger than  ±15 × 10-6 K-1, which are so-called 2D anti-Invar monolayers. Advancing our understanding of materials with exceptionally low or high thermal expansion is of substantial scientific and technological interest, particularly in the development of next-generation electronics at the nanometer or even Ångstrom scale.

2.
Small ; : e2406929, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180443

ABSTRACT

Chemical bath deposition (CBD) is an effective technique used to produce high-quality SnO2 electron transport layers (ETLs) employed in perovskite solar cells (PSCs). By optimizing the CBD process, high-quality SnO2 films are obtained with minimal oxygen vacancies and close energy level alignment with the perovskite layer. In addition, the 3D perovskite layers are passivated with n-butylammonium iodide (BAI), iso-pentylammonium iodide (PNAI), or 2-methoxyethylammonium iodide (MOAI) to form 3D/2D heterojunctions, resulting in defect passivation, suppressing ion migration and improving charge carrier extraction. As a result of these heterojunctions, the power conversion efficiency (PCE) of the PSCs increased from 21.39% for the reference device to 23.70% for the device containing the MOAI-passivated film. The 2D perovskite layer also provides a hydrophobic barrier, thus enhancing stability to humidity. Notably, the PNAI-based device exhibited remarkable stability, retaining approximately 95% of its initial efficiency after undergoing 1000-h testing in an N2 environment at room temperature.

3.
Neuropharmacology ; 260: 110129, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39179173

ABSTRACT

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants.


Subject(s)
Depression , Hypothalamo-Hypophyseal System , Mice, Inbred C57BL , MicroRNAs , Paraventricular Hypothalamic Nucleus , Pituitary-Adrenal System , Stress, Psychological , Animals , MicroRNAs/metabolism , MicroRNAs/genetics , Paraventricular Hypothalamic Nucleus/metabolism , Male , Mice , Hypothalamo-Hypophyseal System/metabolism , Depression/metabolism , Depression/genetics , Pituitary-Adrenal System/metabolism , Stress, Psychological/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Social Defeat
4.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740583

ABSTRACT

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Subject(s)
Cell Movement , Drug Therapy, Combination , Nanoparticles , Neoplasms , Silicon Dioxide , Cell Movement/drug effects , Silicon Dioxide/chemistry , Drug Therapy, Combination/methods , Neoplasms/drug therapy , Nanoparticle Drug Delivery System/chemistry , Nanoparticle Drug Delivery System/therapeutic use , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nanoparticles/ultrastructure , A549 Cells , Microscopy, Electron, Transmission , Humans
5.
Angew Chem Int Ed Engl ; 63(32): e202407193, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38744679

ABSTRACT

As a leading contender to replace lead halide perovskites, tin-based perovskites have demonstrated ever increasing performance in solar cells and light-emitting diodes (LEDs). They tend to be processed with dimethyl sulfoxide (DMSO) solvent, which has been identified as a major contributor to the Sn(II) oxidation during film fabrication, posing a challenge to the further improvement of Sn-based perovskites. Herein, we use NMR spectroscopy to investigate the kinetics of the oxidation of SnI2, revealing that autoamplification takes place, accelerating the oxidation as the reaction progresses. We propose a mechanism consistent with these observations involving water participation and HI generation. Building upon these insights, we have developed low-temperature Sn-based perovskite LEDs (PeLEDs) processed at 60 °C, achieving enhanced external quantum efficiencies (EQEs). Our research underscores the substantial potential of low-temperature DMSO solvent processes and DMSO-free solvent systems for fabricating oxidation-free Sn-based perovskites, shaping the future direction in processing Sn-containing perovskite materials and optoelectronic devices.

6.
Huan Jing Ke Xue ; 45(2): 780-791, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471917

ABSTRACT

Rain-source urban rivers have the characteristics of small water capacity, lack of dynamic water supply, and being easily polluted. This study analyzed the spatial and temporal distribution characteristics of river water quality and the response of characteristic pollutants to rainfall based on daily rainfall data and 21 water quality indicators of nine major river basins in Shenzhen (excluding Shenzhen-Shantou) from 2015 to 2021 by using the single-factor assessment method, comprehensive pollution index method, hierarchical cluster analysis, and Pearson correlation. The results showed that: ① in 2015, the water quality of most sections in the whole region was inferior Class V water. After October 2018, the overall water quality of rivers was greatly improved, which was consistent with the background of Shenzhen's special water control activities in 2018. By 2021, the water quality of approximately 62% of sections reached Class Ⅰ-Ⅲ water standards. ② The water pollution in the densely populated western part of Shenzhen was more serious than that in the eastern part, and the water pollution in the lower reaches of the estuaries and tributaries was more serious than that in the upper reaches. ③ The water quality of the Pingshan River, Guanlan River, Longgang River, and Maozhou River was significantly affected by rainfall. ④ The main characteristic pollution indexes of the Shenzhen River were DO, permanganate index, COD, BOD5, NH4+-N, TP, petroleum, and anionic surfactant. For the Pingshan River and Longgang River, rainfall increased the concentrations of TP and NH4+-N. For the Maozhou River, rainfall increased the concentrations of TP and COD. For the Shenzhen River, rainfall increased the concentrations of COD, TP, and NH4+-N. The above results reveal the spatio-temporal variation in rain-source river water quality in Shenzhen and its response to non-point source pollution caused by rainfall events and provide a scientific reference for building a higher quality water environment in Shenzhen.

7.
Org Biomol Chem ; 22(14): 2819-2823, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38511315

ABSTRACT

An efficient method was developed for the one-pot construction of C-B and C-I via visible light-induced transformation of nitroarenes. This protocol relies on the photochemical properties of nitroarenes under visible light, followed by reduction with B2pin2 and diazotization with tBuONO. An array of arylboronates and iodobenzenes were constructed smoothly after excitation with purple LEDs at room temperature. In addition, the synthetic utility of this method was further demonstrated in the late-stage modification of a drug molecule. The advantages of this strategy include metal-free system, mild reaction conditions and acceptable substrate scope.

8.
Mikrochim Acta ; 191(3): 127, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38334844

ABSTRACT

A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core-shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0-400 µM with a detection limit of 2.78 µM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples.


Subject(s)
Aminophenols , Nanostructures , Oxides , Manganese Compounds , Glucose , Silicon Dioxide
9.
Int J Neuropsychopharmacol ; 26(10): 680-691, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37603290

ABSTRACT

BACKGROUND: Although depression has been a serious neuropsychiatric disorder worldwide, current antidepressants used in clinical practice have various weaknesses, including delayed onset and low rates of efficacy. Recently, the development of new antidepressants from natural herbal medicine has become one of the important research hotspots. Cucurbitacin B is a natural compound widely distributed in the Cucurbitaceae and Cruciferae families and has many pharmacological activities. The present study aimed to investigate whether cucurbitacin B possess antidepressant-like effects in mice. METHODS: The antidepressant-like effects of cucurbitacin B on mice behaviors were explored using the forced swim test, tail suspension test, open field test, sucrose preference test, and a chronic unpredictable mild stress model of depression together. Then, western blotting and immunofluorescence were used to examine the effects of cucurbitacin B on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) signaling cascade and neurogenesis in the hippocampus of mice. Furthermore, BDNF-short hairpin RNA, K252a, and p-chlorophenylalanine methyl ester were adopted together to determine the antidepressant mechanism of cucurbitacin B. RESULTS: It was found that administration of cucurbitacin B indeed produced notable antidepressant-like effects in mice, which were accompanied with significant promotion in both the hippocampal BDNF-TrkB pathway and neurogenesis. The antidepressant mechanism of cucurbitacin B involves the hippocampal BDNF-TrkB system but not the serotonin system. CONCLUSIONS: Cucurbitacin B has the potential to be a novel antidepressant candidate.


Subject(s)
Antidepressive Agents , Brain-Derived Neurotrophic Factor , Depression , Animals , Humans , Mice , Antidepressive Agents/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Depression/drug therapy , Depression/metabolism , Disease Models, Animal , Hippocampus , Stress, Psychological/drug therapy , Stress, Psychological/metabolism
10.
J Affect Disord ; 338: 228-238, 2023 10 01.
Article in English | MEDLINE | ID: mdl-37257779

ABSTRACT

BACKGROUND: The salt-inducible kinase 1 (SIK1)-CREB-regulated transcription co-activator 1 (CRTC1) system in the paraventricular nucleus (PVN) of the hypothalamus has been demonstrated to participate in not only depression neurobiology but also the antidepressant mechanisms of fluoxetine, paroxetine, venlafaxine, and duloxetine. Like fluoxetine and paroxetine, escitalopram is also a well-known selective serotonin (5-HT) reuptake inhibitor (SSRI). However, recently it has been found that escitalopram can modulate a lot of targets other than the 5-HT system. Here, we speculate that escitalopram produces effects on the SIK1-CRTC1 system in the PVN. METHODS: Two mice models of depression (chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS)), various behavioral tests, enzyme linked immunosorbent assay (ELISA), western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer were used together in the present study. RESULTS: It was found that escitalopram administration not only significantly prevented the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis induced by CSDS and CUMS, but also notably reversed the effects of CSDS and CUMS on SIK1, CRTC1, and CRTC1-CREB binding in the PVN of mice. AAV-based genetic knock-down of SIK1 in PVN neurons evidently abolished the antidepressant-like effects of escitalopram in mice. LIMITATION: A shortage of this study is that only rodent models of depression were used, while human samples were not included. CONCLUSIONS: In summary, regulating the SIK1-CRTC1 system in the PVN participates in the antidepressant mechanism of escitalopram, which extends the knowledge of the pharmacological actions of escitalopram.


Subject(s)
Escitalopram , Paraventricular Hypothalamic Nucleus , Mice , Humans , Animals , Paroxetine , Fluoxetine , Serotonin , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Stress, Psychological/drug therapy , Stress, Psychological/metabolism , Depression/drug therapy , Depression/genetics , Depression/metabolism
11.
Int J Neuropsychopharmacol ; 26(10): 655-668, 2023 10 19.
Article in English | MEDLINE | ID: mdl-37025079

ABSTRACT

BACKGROUND: Although thought of as a multimodal-acting antidepressant targeting the serotonin system, more molecules are being shown to participate in the antidepressant mechanism of vortioxetine. A previous report has shown that vortioxetine administration enhanced the expression of rapamycin complex 1 (mTORC1) in neurons. It has been well demonstrated that mTORC1 participates in not only the pathogenesis of depression but also the pharmacological mechanisms of many antidepressants. Therefore, we speculate that the antidepressant mechanism of vortioxetine may require mTORC1. METHODS: Two mouse models of depression (chronic social defeat stress and chronic unpredictable mild stress) and western blotting were first used together to examine whether vortioxetine administration produced reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and medial prefrontal cortex (mPFC). Then, LY294002, U0126, and rapamycin were used together to explore whether the antidepressant effects of vortioxetine in mouse models of depression were attenuated by pharmacological blockade of the mTORC1 system. Furthermore, lentiviral-mTORC1-short hairpin RNA-enhanced green fluorescence protein (LV-mTORC1-shRNA-EGFP) was adopted to examine if genetic blockade of mTORC1 also abolished the antidepressant actions of vortioxetine in mice. RESULTS: Vortioxetine administration produced significant reversal effects against the chronic stress-induced downregulation in the whole mTORC1 signaling cascade in both the hippocampus and mPFC. Both pharmacological and genetic blockade of the mTORC1 system notably attenuated the antidepressant effects of vortioxetine in mice. CONCLUSIONS: Activation of the mTORC1 system in the hippocampus and mPFC is required for the antidepressant actions of vortioxetine in mice.


Subject(s)
Antidepressive Agents , Hippocampus , Mice , Animals , Vortioxetine/pharmacology , Mechanistic Target of Rapamycin Complex 1/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/metabolism , Prefrontal Cortex/metabolism , Sirolimus/pharmacology
12.
Front Public Health ; 11: 1064731, 2023.
Article in English | MEDLINE | ID: mdl-36908401

ABSTRACT

Background: Suicide is the fourth leading cause of death for adolescents, and globally, over 75% of completed suicides occur in low- and middle-income countries (LMICs). Bullying has been proven to be closely related to suicide attempts. However, further understanding of the mechanisms underlying the relationship between bullying and adolescents' suicide attempts is urgently needed. Methods: We used data from the Global School-based Student Health Survey (GSHS) (2010-2017) from 41 LMICs or regions. This study was based on questions assessing bullying victimization, suicide attempts, sleep deprivation, and body mass. Chi-square tests were used to explore the correlations among the main variables. The mediating role of sleep deprivation and the moderating role of body mass index (BMI) were analyzed using PROCESS. Results: The results showed a positive association between bullying victimization and suicide attempts. Sleep deprivation partially mediated the relationship between the frequency of being bullied and suicide attempts. In addition, sleep deprivation played a full or partial mediating role in the relationship between different types of bullying and suicide attempts. BMI moderated the relationships between the frequency of being bullied and suicide attempts, between being made fun of about one's body and sleep deprivation, and between sleep deprivation and suicide attempts. Conclusion: Being bullied has a positive effect on suicide attempts, which is mediated by sleep deprivation and moderated by body mass. The results of this study are consistent with the stress-diathesis model of suicide, suggesting that being bullied is one of the stressors of suicide in adolescents, while sleep deprivation and body mass are susceptibility diatheses of suicide. The results are conducive to identifying adolescents at a high risk of suicide, suggesting that there is a need to pay more attention to bullied adolescents, especially their sleep quality and body mass, and design effective intervention measures to improve the current situation of adolescent suicide in LMICs.


Subject(s)
Bullying , Crime Victims , Humans , Adolescent , Suicide, Attempted , Developing Countries , Sleep Deprivation
13.
Mikrochim Acta ; 190(3): 99, 2023 02 21.
Article in English | MEDLINE | ID: mdl-36809414

ABSTRACT

A versatile DNA nanomachine detection system has been developed via the combination of DNAzyme with catalytic hairpin assembly (CHA) technology for achieving accurate and sensitive detection of lead ions (Pb2+). In the presence of target Pb2+, capture DNA nanomachine formed by AuNP and DNAzyme recognized and reacted with Pb2+, which yielded an "active" DNAzyme, that induced the cleavage of substrate strand, and then released the initiator DNA (TT) for CHA. With the help of the initiator DNA TT, self-powered CHA was activated to achieve the signal amplification reaction in the detection of DNA nanomachine. Meanwhile, the initiator DNA TT was released and hybridized with the other H1 strand to initiate another CHA, replacement, and turnovers, producing enhanced fluorescence signal of fluorophore FAM (excitation 490 nm/emission 520 nm) for sensitive determination of Pb2+. Under the optimized conditions, the DNA nanomachine detection system revealed high selectivity toward Pb2+ in the concentration range 50-600 pM, with the limit of detection (LOD) of 31 pM. Recovery tests demonstrated that the DNA nanomachine detection system has excellent detection capability in real samples. Therefore, the proposed strategy can be extended and act as a basic platform for highly accurate and sensitive detection of various heavy metal ions.


Subject(s)
Biosensing Techniques , DNA, Catalytic , Lead , DNA , Ions
14.
Neuropharmacology ; 227: 109437, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36702294

ABSTRACT

Major depressive disorder is a frequently occurring neuropsychiatric disorder throughout the world. However, the limited and delayed therapeutic efficacy of monoaminergic medications has led to intensive research efforts to develop novel antidepressants. We have previously demonstrated that hippocampal salt-inducible kinase 2 (SIK2) plays a role in the pathogenesis of depression via regulating the downstream CREB-regulated transcription coactivator 1 (CRTC1)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway. HG-9-91-01 is a potent and selective inhibitor of salt-inducible kinases (SIKs). The present study aims to explore whether HG-9-91-01 has antidepressant-like actions in male C57BL/6J mice. The chronic unpredictable mild stress (CUMS) model of depression, various behavioral tests, western blotting, co-immunoprecipitation, immunofluorescence, stereotactic infusion, and viral-mediated genetic knockdown were used together. It was found that hippocampal infusion of HG-9-91-01 induced significant antidepressant-like effects in the CUMS model, accompanied with preventing the enhancement of CUMS on the hippocampal SIK2 expression and cytoplasmic translocation of CRTC1. HG-9-91-01 treatment also reversed the decreasing effects of CUMS on the BDNF signaling cascade and adult neurogenesis in the hippocampus. Moreover, the antidepressant-like actions of HG-9-91-01 in mice required the hippocampal CRTC1-CREB-BDNF pathway. In conclusion, HG-9-91-01 has potential of being a novel antidepressant candidate.


Subject(s)
Brain-Derived Neurotrophic Factor , Depressive Disorder, Major , Mice , Male , Animals , Brain-Derived Neurotrophic Factor/metabolism , Depressive Disorder, Major/drug therapy , Mice, Inbred C57BL , Antidepressive Agents/pharmacology , Sodium Chloride, Dietary , Stress, Psychological/metabolism , Depression/metabolism , Hippocampus , Disease Models, Animal
15.
Expert Syst Appl ; 213: 118841, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36157791

ABSTRACT

The outbreak of COVID-19 brings almost the biggest explosions of scientific literature ever. Facing such volume literature, it is hard for researches to find desired citation when carrying out COVID-19 related research, especially for junior researchers. This paper presents a novel neural network based method, called citation relational BERT with heterogeneous deep graph convolutional network (CRB-HDGCN), for COVID-19 inline citation recommendation task. The CRB-HDGCN contains two main stages. The first stage is to enhance the representation learning of BERT model for COVID-19 inline citation recommendation task through CRB. To achieve the above goal, an augmented citation sentence corpus, which replaces the citation placeholder with the title of the cited papers, is used to lightly retrain BERT model. In addition, we extract three types of sentence pair according citation relation, and establish sentence prediction tasks to further fine-tune the BERT model. The second stage is to learn effective dense vector of nodes among COVID-19 bibliographic graph through HDGCN. The HDGCN contains four layers which are essentially all sub neural networks. The first layer is initial embedding layer which generates initial input vectors with fixed size through CRB and a multilayer perceptron. The second layer is a heterogeneous graph convolutional layer. In this layer, we expand traditional homogeneous graph convolutional network into heterogeneous by subtly adding heterogeneous nodes and relations. The third layer is a deep attention layer. This layer uses trainable project vectors to reweight the node importance simultaneously according to both node types and convolution layers, which further promotes the performance of learnt node vectors. The last decoder layer recovers the graph structure and let the whole network trainable. The recommendation is finally achieved by integrating the high performance heterogeneous vectors learnt from CRB-HDGCN with the query vectors. We conduct experiments on the CORD-19 and LitCovid datasets. The results show that compared with the second best method CO-Search, CRB-HDGCN improves MAP, MRR, P@100 and R@100 with 21.8%, 22.7%, 37.6% and 21.2% on CORD-19, and 29.1%, 25.9%, 15.3% and 11.3% on LitCovid, respectively.

16.
Mol Psychiatry ; 2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36434056

ABSTRACT

Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic-pituitary-adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesised that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioural tests, virus-mediated gene transfer, enzyme-linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signalling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naive mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.

17.
Front Immunol ; 13: 1010526, 2022.
Article in English | MEDLINE | ID: mdl-36389821

ABSTRACT

Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic Escherichia coli represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in Vibrio alginolyticus. Thus, V. alginolyticus is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a V. alginolyticus-Danio rerio infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of V. alginolyticus and has promising use in aquaculture.


Subject(s)
Proteomics , Vibrio alginolyticus , Escherichia coli/metabolism , Complement System Proteins/metabolism , Glycine , Mannitol/pharmacology , Pyruvates/metabolism
18.
Redox Biol ; 58: 102512, 2022 12.
Article in English | MEDLINE | ID: mdl-36306677

ABSTRACT

Pathogenic strains of bacteria are often highly adept at evading serum-induced cell death, which is an essential complement-mediated component of the innate immune response. This phenomenon, known as serum-resistance, is poorly understood, and as a result, no effective clinical tools are available to restore serum-sensitivity to pathogenic bacteria. Here, we provide evidence that exogenous glycine reverses defects in glycine, serine and threonine metabolism associated with serum resistance, restores susceptibility to serum-induced cell death, and alters redox balance and glutathione (GSH) metabolism. More specifically, in Vibrio alginolyticus and Escherichia coli, exogenous glycine promotes oxidation of GSH to GSH disulfide (GSSG), disrupts redox balance, increases oxidative stress and reduces membrane integrity, leading to increased binding of complement. Antioxidant or ROS scavenging agents abrogate this effect and agents that generate or potentiate oxidation stimulate serum-mediated cell death. Analysis of several clinical isolates of E. coli demonstrates that glutathione metabolism is repressed in serum-resistant bacteria. These data suggest a novel mechanism underlying serum-resistance in pathogenic bacteria, characterized by an induced shift in the GSH/GSSG ratio impacting redox balance. The results could potentially lead to novel approaches to manage infections caused by serum-resistant bacteria both in aquaculture and human health.


Subject(s)
Escherichia coli , Glycine , Humans , Glutathione Disulfide/metabolism , Glycine/pharmacology , Glycine/metabolism , Escherichia coli/metabolism , Glutathione/metabolism , Oxidation-Reduction , Oxidative Stress , Cell Death
19.
Bioprocess Biosyst Eng ; 45(7): 1137-1147, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35624323

ABSTRACT

Solid-phase microbial fuel cell (SMFC) can accelerate the removal of organic pollutants through the electrons transfer between microorganisms and anodes in the process of generating electricity. Thus, the characteristics of the anode material will affect the performance of SMFCs. In this study, corn stem (CS) is first calcined into a 3D macroporous electrode, and then modified with carbon nanotubes (CNTs) through electrochemical deposition method. Scanning electron microscope analysis showed the CS/CNT anode could increase the contact area on the surface. Furthermore, electrochemical impedance spectroscopy and cyclic voltammetry analysis indicated the electrochemical double-layer capacitance of the CS/CNT anode increased while its internal resistance decreased significantly. These characteristics are crucial for increasing bacterial adhesion capability and electron transfer rate. The maximum output voltage of the SMFC with CS/CNT anode was 158.42 mV, and the removal rate of petroleum hydrocarbon (PH) reached 42.17%, 2.72 times that of unmodified CS. In conclusion, CNT-modified CS is conducive to improve electron transfer rate and microbial attachment, enhancing the removal efficiency of PH in soil.


Subject(s)
Bioelectric Energy Sources , Nanotubes, Carbon , Petroleum , Bioelectric Energy Sources/microbiology , Electrodes , Hydrocarbons , Nanotubes, Carbon/chemistry , Soil , Zea mays
20.
Biochem Pharmacol ; 202: 115097, 2022 08.
Article in English | MEDLINE | ID: mdl-35609645

ABSTRACT

Depression is a very prevalent psychiatric disorder which threats nearly one in six of the population in this world. To date, the pathogenesis of depression remains elusive and is thought to depend on multiple factors in which chronic stress is critical. Currently, it has been demonstrated that besides monoaminergic dysfunction, depression is accompanied by several other important pathological phenomena such as impaired neurogenesis and decreased brain-derived neurotrophic factor (BDNF)-cAMP response element binding protein (CREB) signaling cascade in the hippocampus. F3/Contactin is a cell-adhesion molecule which has been reported to correlate with hippocampal neurogenesis and BDNF-CREB signaling. Here we assumed that F3/Contactin may be implicated in depression, and various methods including western blotting, immunofluorescence, virus-mediated gene transfer and chronic stress models of depression were adopted together. It was found that both chronic restraint stress (CRS) and chronic social defeat stress (CSDS) significantly decreased the expression of F3/Contactin in the hippocampus. Adeno-associated virus (AAV)-mediated over-expression of hippocampal F3/Contactin notably prevented the CRS-induced and CSDS-induced depressive-like behaviors in mice. Moreover, hippocampal F3/Contactin over-expression also fully reversed the CRS-induced and CSDS-induced dysfunction in the hippocampal BDNF-CREB signaling and neurogenesis of mice. Furthermore, administration of vortioxetine, a multimodal-acting antidepressant, fully ameliorated the inhibitory actions of both CRS and CSDS on the hippocampal F3/Contactin expression. In contrast, AAV-mediated knockdown of hippocampal F3/Contactin significantly abolished the protecting effects of vortioxetine against CRS and CSDS. Collectively, hippocampal F3/Contactin is implicated in depression and could be a novel antidepressant target.


Subject(s)
Antidepressive Agents , Brain-Derived Neurotrophic Factor , Vortioxetine , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Brain-Derived Neurotrophic Factor/genetics , Brain-Derived Neurotrophic Factor/metabolism , Contactins/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Depression/drug therapy , Depression/etiology , Disease Models, Animal , Hippocampus , Humans , Mice , Mice, Inbred C57BL , Stress, Psychological/complications , Stress, Psychological/metabolism , Vortioxetine/pharmacology
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