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Abstract Lung metastasis is the major cause of death in patients with triple-negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) represent the M2-like phenotype with potent immunosuppressive activity, and play a pro-tumor role in TNBC lung metastasis. Sohlh2 belongs to the basic helix-loop-helix transcription factor family. However, its role in macrophages polarization remains unknown, especially in TNBC progression. Here we demonstrated that Sohlh2 overexpression promoted M2 macrophage polarization. Moreover, high expression of Sohlh2 in M2-like macrophage enhanced TNBC cell growth, migration and lung metastasis in vivo and in vitro. Mechanistically, we revealed that Sohlh2 functioned through up-regulating LXRα, ABCA1, ABCG1 expression and disturbing the lipid homeostasis on the membrane of macrophages. Sohlh2 could directly bind to the promoter of LXRα and promote its transcription activity. E3 ubiquitin ligase TRIM21 promoted Sohlh2 ubiquitination and degradation, and suppressed M2 macrophage polarization and TNBC progression. Collectively, our findings suggested that Sohlh2 in macrophage could be a novel therapeutic target for TNBC metastatic treatment.

Thirst and water intake are regulated by the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO), located around the anteroventral third ventricle, which plays a critical role in sensing dynamic changes in sodium and water balance in body fluids. Meanwhile, neural circuits involved in thirst regulation and intracellular mechanisms underlying the osmosensitive function of OVLT and SFO are reviewed. Having specific Nax channels in the glial cells and other channels (such as TRPV1 and TRPV4), the OVLT and SFO detect the increased Na+ concentration or hyperosmolality to orchestrate osmotic stimuli to the insular and cingulate cortex to evoke thirst. Meanwhile, the osmotic stimuli are relayed to the supraoptic nucleus (SON) and paraventricular nucleus of the hypothalamus (PVN) via direct neural projections or the median preoptic nucleus (MnPO) to promote the secretion of vasopressin which plays a vital role in the regulation of body fluid homeostasis. Importantly, the vital role of OVLT in sleep-arousal regulation is discussed, where vasopressin is proposed as the mediator in the regulation when OVLT senses osmotic stimuli.

Tobacco has a strong cadmium (Cd) enrichment capacity, meaning that it can absorb large quantities from the environment, but too much Cd will cause damage to the plant. It is not yet clear how the plant can dynamically respond to Cd stress. Here, we performed a temporal transcriptome analysis of tobacco roots under Cd treatment from 0 to 48 h. The number of differentially expressed genes (DEGs) was found to change significantly at 3 h of Cd treatment, which we used to define the early and middle stages of the Cd stress response. The gene ontology (GO) term analysis indicates that genes related to photosynthesis and fatty acid synthesis were enriched during the early phases of the stress response, and in the middle phase biological process related to metal ion transport, DNA damage repair, and metabolism were enriched. It was also found that plants use precursor mRNA (pre-mRNA) processes to first resist Cd stress, and with the increasing of Cd treatment time, the overlapped genes number of DEGs and DAS increased, suggesting the transcriptional levels and post-transcriptional level might influence each other. This study allowed us to better understand how plants dynamically respond to cadmium stress at the transcriptional and post-transcriptional levels and provided a reference for the screening of Cd-tolerant genes in the future.

Premenstrual syndrome (PMS), a recurrent and moderate disorder that occurs during the luteal phase of the menstrual cycle and quickly resolves after menstruation, is characterized by somatic and emotional discomfort that can be severe enough to impair daily activities. Current therapeutic drugs for PMS such as selective serotonin reuptake inhibitors are not very satisfying. As a critical pineal hormone, melatonin has increasingly been suggested to modulate PMS symptoms. In this review, we update the latest progress on PMS-induced sleep disturbance, mood changes, and cognitive impairment and provide possible pathways by which melatonin attenuates these symptoms. Moreover, we focus on the role of melatonin in PMS molecular mechanisms. Herein, we show that melatonin can regulate ovarian estrogen and progesterone, of which cyclic fluctuations contribute to PMS pathogenesis. Melatonin also modulates gamma-aminobutyric acid and the brain-derived neurotrophic factor system in PMS. Interpreting the role of melatonin in PMS is not only informative to clarify PMS etiology but also instructive to melatonin and its receptor agonist application to promote female health. As a safe interaction, melatonin treatment can be effective in alleviating symptoms of PMS. However, symptoms such as sleep disturbance, depressive mood, cognitive impairment are not specific and can be easily misdiagnosed. Connections between melatonin receptor, ovarian steroid dysfunction, and PMS are not consistent among past studies. Before final conclusions are drawn, more well-organized and rigorous studies are recommended.

The pectin methylesterases (PMEs) play multiple roles in regulating plant development and responses to various stresses. In our study, a total of 121 PME genes were identified in the tobacco genome, which were clustered into two groups based on phylogenetic analysis together with Arabidopsis members. The investigations of gene structure and conserved motif indicated that exon/intron and motif organizations were relatively conserved in each group. Additionally, several stress-related elements were identified in the promoter region of these genes. The survey of duplication events revealed that segmental duplications were critical to the expansion of the PME gene family in tobacco. The expression profiles analysis revealed that these genes were expressed in various tissues and could be induced by diverse abiotic stresses. Notably, NtPME029 and NtPME043, were identified as homologues with AtPME3 and AtPME31, respectively. Furthermore, NtPME029 was highly expressed in roots and the over-expression of the NtPME029 gene could promote the development of roots. While NtPME043 could be induced by salt and ABA treatments, and the over-expression of the NtPME043 gene could significantly enhance the salt-stress tolerance in tobacco. Overall, these findings may shed light on the biological and functional characterization of NtPME genes in tobacco.

Alcohol use disorder (AUD) is a high-risk psychiatric disorder and a key cause of death and disability in individuals. In the development of AUD, there is a connection known as the microbiota-gut-brain axis, where alcohol use disrupts the gut barrier, resulting in changes in intestinal permeability as well as the gut microbiota composition, which in turn impairs brain function and worsens the patient’s mental status and gut activity. Potential mechanisms are explored by which alcohol alters gut and brain function through the effects of the gut microbiota and their metabolites on immune and inflammatory pathways. Alcohol and microbiota dysregulation regulating neurotransmitter release, including DA, 5-HT, and GABA, are also discussed. Thus, based on the above discussion, it is possible to speculate on the gut microbiota as an underlying target for the treatment of diseases associated with alcohol addiction. This review will focus more on how alcohol and gut microbiota affect the structure and function of the gut and brain, specific changes in the composition of the gut microbiota, and some measures to mitigate the changes caused by alcohol exposure. This leads to a potential intervention for alcohol addiction through fecal microbiota transplantation, which could normalize the disruption of gut microbiota after AUD.

The NAC (NAM, ATAF1/2, and CUC2) family acts as one of the largest families of the transcription factor in the plant kingdom and was revealed to function as the important regulators in various environmental stresses. However, a few studies were reported about the biofunctions of the NAC transcription factor in tobacco. In the current study, we characterized a novel NAC transcription factor encoding the gene NtNAC053 in tobacco, which was significantly up-regulated when exposed to salt and drought treatments. The results of cis-acting elements analysis suggested that the promoter region of NtNAC053 gene possesses a number of stress-responsive elements, and this gene could be induced by exogenous abscisic acid (ABA) treatment. Moreover, the NtNAC053–GFP fusion protein was localized in the cell nucleus and possessed a transactivation domain in its C-terminal, implying that NtNAC053 may undertake as a transcriptional activator in tobacco. Notably, the overexpression of NtNAC053 in tobacco resulted in hypersensitivity to ABA treatment. Furthermore, these overexpression lines showed significantly enhanced tolerances to drought and salt stresses. Under salt and drought stresses, these overexpression lines possessed higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Interestingly, the expressions of putative stress-related genes, including NtCOR15A, NtRAB18, NtDREB1A, NtERF5, NtKAT2, and NtERD11, were up-regulated in these overexpression lines when subjected to salt and drought stresses. The clues provided in our study suggested that the NtNAC053 gene encodes a novel NAC transcription factor and could confer the drought and salt stress tolerances by inspiring the downstream stress-responsive genes and antioxidant system in tobacco.

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.

The bZIP proteins comprise one of the largest transcription factor families and play important roles in plant growth and development, senescence, metabolic reactions, and stress responses. In this study, 49 bZIP transcription factor-encoding genes (StbZIP genes) on the potato genome were identified and analyzed. The 49 StbZIP genes, which are located on 12 chromosomes of the potato genome, were divided into 11 subgroups together with their Arabidopsis homologs based on the results of phylogenetic analysis. Gene structure and protein motif analysis revealed that members from the same subgroup often possessed similar exon/intron structures and motif organizations, further supporting the results of the phylogenetic analysis. Syntenic analysis indicated the existence of gene duplication events, which might play an important role in the expansion of the bZIP gene family in potato. Expressions of the StbZIP genes were analyzed in a variety of tissues via RNA-Seq data, suggesting functional diversity. Several StbZIP genes were found to be induced by different stress conditions. For example, the expression of StbZIP25, the close homolog of AtbZIP36/ABF2, was significantly upregulated by salt stress treatments. The StbZIP25 protein was found to be located in the nucleus and function as a transcriptional activator. Overexpression of StbZIP25 enhanced salt tolerance in Arabidopsis. The results from this study imply potential roles of the bZIP family genes in the stress response of potato.

The inflorescence deficient in abscission-like (IDL) genes have been shown to play critical roles in floral organ abscission, lateral root formation and various stress responses in Arabidopsis. The IDL gene family has been characterized in a number of plant species, while limited information is available about IDL genes of tobacco. In the current study, 15 NtIDL members were identified in the tobacco genome, and were classified into six groups together with IDL members from other species. Evolution analysis suggested that the NtIDL members form group VI might have originated from duplication events. Notably, NtIDL06 shared high similarities with AtIDA in the EPIP sequence, and its encoding gene was highly expressed in the abscission zone of flowers at late developmental stages, implying that NtIDL06 might regulate tobacco flower abscission. In addition, the results from cis-elements analysis of promoters and expression after stress treatments suggested that NtIDL members might be involved in various stress responses of tobacco. The results from this study provide information for further functional analysis related to flower abscission and stress responses of NtIDL genes.

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with multiple predisposing factors and complicated pathogenesis. Aβ peptide is one of the most important pathogenic factors in the etiology of AD. Accumulating evidence indicates that the imbalance of Aβ production and Aβ clearance in the brain of AD patients leads to Aβ deposition and neurotoxic Aβ oligomer formation. Melatonin shows a potent neuroprotective effect and can prevent or slow down the progression of AD, supporting the view that melatonin is a potential therapeutic molecule for AD. Melatonin modulates the regulatory network of secretase expression and affects the function of secretase, thereby inhibiting amyloidogenic APP processing and Aβ production. Additionally, melatonin ameliorates Aβ-induced neurotoxicity and probably promotes Aβ clearance through glymphatic-lymphatic drainage, BBB transportation and degradation pathways. In this review, we summarize and discuss the role of melatonin against Aβ-dependent AD pathogenesis. We explore the potential cellular and molecular mechanisms of melatonin on Aβ production and assembly, Aβ clearance, Aβ neurotoxicity and circadian cycle disruption. We summarize multiple clinical trials of melatonin treatment in AD patients, showing that melatonin has a promising effect on improving sleep quality and cognitive function. This review aims to stimulate further research on melatonin as a potential therapeutic agent for AD.

The NAC (NAM, ATAF1/2, and CUC2) transcription factors comprise one of the largest transcription factor families in plants and play important roles in stress responses. However, little is known about the functions of potato NAC family members. Here we report the cloning of a potato NAC transcription factor gene StNAC053, which was significantly upregulated after salt, drought, and abscisic acid treatments. Furthermore, the StNAC053-GFP fusion protein was found to be located in the nucleus and had a C-terminal transactivation domain, implying that StNAC053 may function as a transcriptional activator in potato. Notably, Arabidopsis plants overexpressing StNAC053 displayed lower seed germination rates compared to wild-type under exogenous ABA treatment. In addition, the StNAC053 overexpression Arabidopsis lines displayed significantly increased tolerance to salt and drought stress treatments. Moreover, the StNAC053-OE lines were found to have higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) under multiple stress treatments. Interestingly, the expression levels of several stress-related genes including COR15A,DREB1A, ERD11, RAB18, ERF5, and KAT2, were significantly upregulated in these StNAC053-overexpressing lines. Taken together, overexpression of the stress-inducible StNAC053 gene could enhance the tolerances to both salt and drought stress treatments in Arabidopsis, likely by upregulating stress-related genes.

Zinc finger homeodomain (ZF-HD) transcription factors play significant roles in plant growth and responses to environmental stresses. In this study, 32 ZF-HD genes identified in the tobacco (Nicotiana tabacum L.) genome were divided into six groups according to phylogenetic analysis with Arabidopsis and tomato ZF-HD members. An examination of gene structures and conserved motifs revealed the relatively conserved exon/intron structures and motif organization within each subgroup. In addition, various stress-related elements are found in the promoter region of these genes. The expression profiling analysis revealed that NtZF-HD genes expressed in different tissues and could be induced by several abiotic stresses. Notably, NtZF-HD21 was highly expressed in response to the drought treatments. Subcellular localization analysis and a virus-induced gene silencing (VIGS) experiment were performed to investigate the potential functions of NtZF-HD21. The subcellular localization indicated that NtZF-HD21 is a nuclear protein. Furthermore, gene silencing of the NtZF-HD21 gene reduced the drought resistance of tobacco. These findings provide insights for further biological functional analyses of the NtZF-HD genes in tobacco.

We report a principle prototype of space animal cell perfusion culture and observation. Unlike previous work, our cell culture system cannot only realize microfluidic and temperature controlling, automatic observation, and recording but also meet an increasing cell culture at large scale operation and overcome shear force for animal cells. A key component in the system is ingenious structural fused silica cell culture cavity with the wedge-shaped connection. Finite volume method (FVM) is applied to calculate its multipoint flow field, pressure field, axial velocity, tangential velocity, and radial velocity. In order to provide appropriate flow rate, temperature, and shear force for space animal cell culture, a closed-loop microfluidic circuit and proportional, integrating, and differentiation (PID) algorithm are employed. This paper also illustrates system architecture and operating method of the principle prototype. The dynamic culture, autofocus observation, and recording of M763 cells are performed successfully within 72 h in the laboratory environment. This research can provide a reference for space flight mission that carries an apparatus with similar functions.

Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) and loss of neurons. Recently, a growing body of evidences have indicated that as a herbal compound naturally derived from grapes, resveratrol modulates the pathophysiology of AD, however, with a largely unclear mechanism. Therefore, we aimed to investigate the protection of resveratrol against the neurotoxicity of β-amyloid peptide 25-35 (Aβ(25-35)) and further explore its underlying mechanism in the present study. PC12 cells were injuried by Aβ(25-35), and resveratrol at different concentrations was added into the culture medium. We observed that resveratrol increased cell viability through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) colorimetric assays. Flow cytometry indicated the reduction of cell apoptosis by resveratrol. Moreover, resveratrol also stabilized the intercellular Ca(2+) homeostasis and attenuated Aβ(25-35) neurotoxicity. Additionally, Aβ(25-35)-suppressed silent information regulator 1 (SIRT1) activity was significantly reversed by resveratrol, resulting in the downregulation of Rho-associated kinase 1 (ROCK1). Our results clearly revealed that resveratrol significantly protected PC12 cells and inhibited the β-amyloid-induced cell apoptosis through the upregulation of SIRT1. Moreover, as a downstream signal molecule, ROCK1 was negatively regulated by SIRT1. Taken together, our study demonstrated that SIRT1-ROCK1 pathway played a critical role in the pathomechanism of AD.

Signal demodulation method of a frequency output resonant gyroscope is studied in this study. It has been a major problem of frequency micro gyroscopes. The detection elements of frequency gyroscopes are two double-ended tuning forks (DETF). The vibratory response of DETF is a periodic signal modulated by both amplitude and frequency. According to the characteristic that the amplitude and frequency of the gyro signal vary continuously with time, the signal demodulation algorithm is designed based on instantaneous frequency analysis. Hilbert transform is used to solve the instantaneous frequency. The algorithm is programmed in digital signal processor (DSP) and a test circuit board is made. Experimental test demonstrates that the demodulation circuit has a high precision and linearity, and the correlation coefficient between input signals and demodulation results achieves as much as 0.99999998. The demodulation method is proved to be feasible. This study provides a new train of thought for the study of the signal demodulation method of frequency micro gyroscopes and brings a new direction for the signal analysis of resonant sensors. [ABSTRACT FROM AUTHOR]

The duplicated grass APETALA1/ FRUITFULL ( AP1/ FUL) genes have distinct but overlapping patterns of expression, suggesting their discrete roles in transition to flowering, specification of spikelet meristem identity and specification of floral organ identity. In this study, we analyzed the expression patterns and functions of four AP1/ FUL paralogs ( BdVRN1, BdFUL2, BdFUL3 and BdFUL4) in Brachypodium distachyon, a model plant for the temperate cereals and related grasses. Among the four genes tested, only BdVRN1 could remember the prolonged cold treatment. The recently duplicated BdVRN1 and BdFUL2 genes were expressed in a highly consistent manner and ectopic expressions of them caused similar phenotypes such as extremely early flowering and severe morphological alterations of floral organs, indicating their redundant roles in floral transition, inflorescence development and floral organ identity. In comparison, ectopic expressions of BdFUL3 and BdFUL4 only caused a moderate early flowering phenotype, suggesting their divergent function. In yeast two-hybrid assay, both BdVRN1 and BdFUL2 physically interact with SEP proteins but only BdFUL2 is able to form a homodimer. BdVRN1 also interacts weakly with BdFUL2. Our results indicate that, since the separation of AP1/ FUL genes in grasses, the process of sub- or neo-functionalization has occurred and paralogs function redundantly and/or separately in flowering competence and inflorescence development. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. [ABSTRACT FROM AUTHOR]

In this paper, the application of weak signal detection based on chaotic oscillator is studied in a MEMS resonant beam sensor. Chaotic oscillator can detect weak signal which is submerged in the background of large noise. According to the frequency and phase characteristic of the output vibrating signal, reference current signal with fixed frequency difference and same phase to the output signal is set. Frequency and phase of the signal are fixed by detection resistor which works as a multiplier. By calculating the maximum Lyapunov exponent, detection threshold is obtained, and motion change of detection system is monitored. The results of numerical simulation and experiment show that this method can effectively detect the weak resonant signal and find the resonant frequency accurately by setting the threshold of the chaotic oscillator, and it is immune to the noise. [ABSTRACT FROM AUTHOR]

Schizophrenia is a heterogeneous psychotic illness and its etiology remains poorly understood. Recent studies have suggested that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics appear to slow progressive morphological brain changes. In addition, the atypical antipsychotics were reported to have a superior therapeutic efficacy in treating schizophrenia and have a low incidence of extrapyramidal side effects (EPS) compared to typical antipsychotics. However, the mechanisms of atypical antipsychotics in treating schizophrenia and the basis for differences in their clinical effects were still totally unknown. In the present study, we investigated whether paliperidone shows protective effects on SK-N-SH cells from cell toxicity induced by exposure to glutamate. We examined the effects of the drugs on cell viability (measured by MTT metabolism assay and lactate dehydrogenase (LDH) activity assay), apoptosis rate, ROS levels and gene expression and phosphorylation of Akt1 and GSK3β. The results showed that paliperidone significantly increases the cell viability by MTT and LDH assays (p < 0.05), in contrast to the typical antipsychotic (haloperidol), which had little neuroprotective activity. Moreover, paliperidone retarded the glutamate-mediated promotion of ROS and the rate of apoptosis (p < 0.05). In addition, paliperidone also effectively reversed glutamate-induced decreases of gene expression and phosphorylation of Akt1 and GSK3β (both p < 0.05). Our results demonstrated that paliperidone could effectively protect SK-N-SH cells from glutamate-induced damages via Akt1/GSK3β signaling pathway. [ABSTRACT FROM AUTHOR]