Mimicking the retinal neuron functions by a photoresponsive single transistor with a double gate.

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost.

Transcriptomic analysis of salt-tolerant and sensitive high-yield japonica rice (Oryza sativa L.) reveals complicated salt-tolerant mechanisms.

Developing and cultivating rice varieties is a potent strategy for reclaiming salinity-affected soils for rice production. Nevertheless, the molecular mechanisms conferring salt tolerance, especially in conventional high-yield japonica rice varieties, remain obscure. In this study, Zhendao 23309 (ZD23309) exhibited significantly less grain yield reduction under a salt stress gradient than the control variety Wuyunjing 30 (WYJ30). High positive correlations between grain yield and dry matter accumulation at the jointing, heading and maturity stages indicated that early salt tolerance performance is a crucial hallmark for yield formation. After a mild salt stress (85 mM NaCl) of young seedlings, RNA sequencing (RNA-seq) of shoot and root separately identified a total of 1952 and 3647 differentially expressed genes (DEGs) in ZD23309, and 2114 and 2711 DEGs in WYJ30, respectively. Gene ontology (GO) analysis revealed numerous DEGs in ZD23309 that play pivotal roles in strengthening salt tolerance, encompassing the response to stimulus (GO:0050896) in shoots and nucleoside binding (GO:0001882) in roots. Additionally, distinct expression patterns were observed in a fraction of genes in the two rice varieties under salt stress, corroborating the efficacy of previously reported salt tolerance genes. Our research not only offers fresh insights into the differences in salt stress tolerance among conventional high-yield rice varieties but also unveils the intricate nature of salt tolerance mechanisms. These findings lay a solid groundwork for deciphering the mechanisms underlying salt tolerance.

Jaceosidin attenuates the progression of hepatic fibrosis by inhibiting the VGLL3/HMGB1/TLR4 signaling pathway.

BACKGROUND: Jaceosidin (JA) is a natural flavone extracted from Artemisia that is used as a food and traditional medicinal herb. It has been reported to possess numerous biological activities. However, the regulatory mechanisms underlying amelioration of hepatic fibrosis remain unclear. HYPOTHESIS/PURPOSE: We hypothesized that jaceosidin acid (JA) modulates hepatic fibrosis and inflammation. METHODS: Thioacetamide (TAA) was used to establish an HF mouse model. In vitro, mouse primary hepatocytes and HSC-T6 cells were induced by TGF-ß, whereas mouse peritoneal macrophages received a treatment lipopolysaccharide (LPS)/ATP. RESULTS: JA decreased serum transaminase levels and improved hepatic histological pathology in TAA-treated mice stimulated by TAA. Moreover, the expression of pro-fibrogenic biomarkers associated with the activation of liver stellate cells was downregulated by JA. Likewise, JA down-regulated the expression of vestigial-like family member 3 (VGLL3), high mobility group protein B1 (HMGB1), toll-like receptors 4 (TLR4), and nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3), thereby inhibiting the inflammatory response and inhibiting the release of mature-IL-1ß in TAA-stimulated mice. Additionally, JA suppressed HMGB1 release and NLRP3/ASC inflammasome activation in LPS/ATP-stimulated murine peritoneal macrophages. JA decreases the expression of pro-fibrogenic biomarkers related to liver stellate cell activation and inhibits inflammasome activation in mouse primary hepatocytes. It also down-regulated α-SMA and VGLL3 expressions and also suppressed inflammasome activation in HSC-T6 cells. VGLL3 and α-SMA expression levels were decreased in TGF-ß-stimulated HSC-T6 cells following Vgll3 knockdown. In addition, the expression levels of NLRP3 and cleaved-caspase-1 were decreased in Vgll3-silenced HSC-T6 cells. JA enhanced the inhibitory effects on Vgll3-silenced HSC-T6 cells. Finally, Vgll3 overexpression in HSC-T6 cells affected the expression levels of α-SMA, NLRP3, and cleaved-caspase-1. CONCLUSION: JA effectively modulates hepatic fibrosis by suppressing fibrogenesis and inflammation via the VGLL3/HMGB1/TLR4 axis. Therefore, JA may be a candidate therapeutic agent for the management of hepatic fibrosis. Understanding the mechanism of action of JA is a novel approach to hepatic fibrosis therapy.

Simplified panicle fertilization is applicable to japonica cultivars, but splits are preferred in indica rice for a higher paddy yield under wheat straw return.

Introduction: The panicle fertilization strategy for japonica and indica rice under wheat straw return (SR) has not been updated, especially on the elaboration of their impacts on spikelet differentiation and degeneration. This study aimed to verify the hypothesis that SR increases spikelet number by reducing spikelet degeneration and to explore the possibility of simplifying panicle fertilization. Methods: In three consecutive years, four varieties of japonica and indica rice were field-grown in Yangzhou, Jiangsu Province, China. Six panicle fertilization rates and split treatments were applied to SR and no straw return (NR) conditions. Results: The results showed that SR promoted rice yield significantly by 3.77%, and the highest yields were obtained under the T2 (split panicle fertilization at the panicle initiation (PI) and spikelet primordium differentiation (SPD) stages) and T1 (panicle fertilization only at the PI stage) treatments, for indica and japonica rice, respectively. Correlation and path analysis revealed that the number of spikelets per panicle was the most attributable to yield variation. SR significantly increased the concentration of alkali hydrolyzable N in the soil 40 days after rice transplantation, significantly increased the nitrogen accumulation per stem (NA) during the SPD-pollen mother cell meiosis (PMC) stage, and increased the brassinosteroids level in the young panicles at the PMC stage. SR also reduced the degeneration rate of spikelets (DRS) and increased the number of surviving spikelets (NSS). The dry matter accumulation per stem was more important to increasing the NA in japonica rice at the PMC stage, whereas NA was more affected by the N content than the dry matter accumulation in indica rice. In japonica rice, panicle N application once only at the PI stage combined with the N released from SR was enough to improve the plant N content, reduce the DRS, and increase the NSS. For indica rice, split application of N panicle fertilization at both the PI and SPD stages was still necessary to achieve a maximum NSS. Discussion: In conclusion, under wheat SR practice, panicle fertilization could be simplified to once in japonica rice with a significant yield increase, whereas equal splits might still be optimal for indica rice.

Validation of Novel Reference Genes in Different Rice Plant Tissues through Mining RNA-Seq Datasets.

Reverse transcription quantitative real-time PCR (RT-qPCR) is arguably the most prevalent and accurate quantitative gene expression analysis. However, selection of reliable reference genes for RT-qPCR in rice (Oryza sativa) is still limited, especially for a specific tissue type or growth condition. In this study, we took the advantage of our RNA-seq datasets encompassing data from five rice varieties with diverse treatment conditions, identified 12 novel candidate reference genes, and conducted rigorous evaluations of their suitability across typical rice tissues. Comprehensive analysis of the leaves, shoots, and roots of two rice seedlings subjected to salt (30 mmol/L NaCl) and drought (air-dry) stresses have revealed that OsMED7, OsACT1, and OsOS-9 were the robust reference genes for leaf samples, while OsACT1, OsZOS3-23, and OsGDCP were recommended for shoots and OsMED7, OsOS-9, and OsGDCP were the most reliable reference genes for roots. Comparison results produced by different sets of reference genes revealed that all these newly recommended reference genes displayed less variation than previous commonly used references genes under the experiment conditions. Thus, selecting appropriate reference genes from RNA-seq datasets leads to identification of reference genes suitable for respective rice tissues under drought and salt stress. The findings offer valuable insights for refining the screening of candidate reference genes under diverse conditions through the RNA-seq database. This refinement serves to improve the accuracy of gene expression in rice under similar conditions.

The regulatory role and mechanism of exosomes in hepatic fibrosis.

Globally, the prevalence and fatality rates of liver disorders are on the rise. Among chronic liver conditions, hepatic fibrosis stands out as a central pathological process. Despite this, approved treatments for hepatic fibrosis are currently lacking. Exosomes, small extracellular vesicles secreted by various cell types, play a significant role in intercellular communication and have emerged as essential mediators in liver fibrosis. In this regard, this review compiles the mechanisms through which exosomes regulate hepatic fibrosis, encompassing diverse targets and signaling pathways. Furthermore, it delves into the regulatory impact of exosomes modulated by natural plant-derived, endogenous, and synthetic compounds as potential therapeutic strategies for addressing hepatic fibrosis.

The Explanation of Photopic Luminous Efficiency Curve by Using Both of the Cones' Optical Fiber Coupling Effects and the Absorption of L Cones.

In this paper, we build four-part cone models to explore the coupling effect of seven cone fiber couplers. Moreover, this is the first study of the coupling effect of four layers of biological couplers in animals and other biological lives. We simulate the four layers cone couplers by using the beam propagation method, and we assume the input beam is located at the outer fiber of the central cone. Our simulation results showed that there are two wavelength regions (short and long wavelength regions) with the strongest coupling, where the most power of input optical powers of the central cones will transfer to the six surrounding cones after transmitting through the four layers of cone couplers. However, within a wavelength region of ±75 nm near to the peak wavelengths, located in the yellow-green wavelength range, the splitting ratios at the output of the outer segment of the central cone are always greater than the sum of the splitting ratios of the six surrounding cones. These cone couplers may play an important role in color preprocessing (e.g., doing opponent color processing partially). The cone fiber coupler effect and light absorption of cones are considered separately in our models. By taking account of both the cone fiber coupling effect and absorption of outer segment of L cone, we find the multiplication of the relative optical power of cone couplers, the spectral sensitivity data of the L cone, and a normalized coefficient that matches with the photopic luminous efficiency of the human eye well. This is the attempt to use both the cone fiber coupling effect and the absorption of L cones to explain the photopic luminous efficiency. The splitting ratios of the central cones are greater than 80% at peak wavelengths located in the yellow-green wavelength range, and this can help to explain why the human eye is more sensitive to green light.

Genetic and molecular factors in determining grain number per panicle of rice.

It was suggested that the most effective way to improve rice grain yield is to increase the grain number per panicle (GN) through the breeding practice in recent decades. GN is a representative quantitative trait affected by multiple genetic and environmental factors. Understanding the mechanisms controlling GN has become an important research field in rice biotechnology and breeding. The regulation of rice GN is coordinately controlled by panicle architecture and branch differentiation, and many GN-associated genes showed pleiotropic effect in regulating tillering, grain size, flowering time, and other domestication-related traits. It is also revealed that GN determination is closely related to vascular development and the metabolism of some phytohormones. In this review, we summarize the recent findings in rice GN determination and discuss the genetic and molecular mechanisms of GN regulators.

The plant streptolysin S (SLS)-associated gene B confers nitroaromatic tolerance and detoxification.

Nitroaromatic compounds, as the important chemical feedstock, have caused widespread environmental contaminations, and exhibited high toxicity and mutagenic activity to nearly all living organisms. The clean-up of nitroaromatic-contaminated soil and water has long been a major international concern. Here, we uncovered the role of a novel nitroreductase family gene, streptolysin S (SLS)-associated gene B (SagB), in enhancing nitroaromatic tolerance and detoxification of plants, and its potential application in phytoremediation of nitroaromatic contaminations. The expression of both the Arabidopsis and rice SagB genes is significantly induced by multiple hazardous nitroaromatic substances, including explosive pollutant 2,4,6-trinitrotoluene (TNT), natural compound 1-nitropyrene (1-NP) and herbicide pendimethalin (Pen). In vitro and in vivo evidences revealed that plant SagBs possess activities in degradation of these nitroaromatic substances. Arabidopsis and rice transgenic assays suggested that plant SagB genes increase tolerance and detoxification of nitroaromatic through facilitating its transformation to the amino derivative. More importantly, overexpression of plant SagBs increase their ability in TNT uptake, and remove more TNT from the growth culture. Our findings shed novel insights into a plant endogenous nitroreductase-mediated nitroaromatic tolerance and detoxification, and provide a new gene target for phytoremediation of nitroaromatic-contaminated environments.

OsCOMT, encoding a caffeic acid O-methyltransferase in melatonin biosynthesis, increases rice grain yield through dual regulation of leaf senescence and vascular development.

Melatonin, a natural phytohormone in plants, plays multiple critical roles in plant growth and stress responses. Although melatonin biosynthesis-related genes have been suggested to possess diverse biological functions, their roles and functional mechanisms in regulating rice grain yield remain largely unexplored. Here, we uncovered the roles of a caffeic acid O-methyltransferase (OsCOMT) gene in mediating rice grain yield through dual regulation of leaf senescence and vascular development. In vitro and in vivo evidence revealed that OsCOMT is involved in melatonin biosynthesis. Transgenic assays suggested that OsCOMT significantly delays leaf senescence at the grain filling stage by inhibiting degradation of chlorophyll and chloroplast, which, in turn, improves photosynthesis efficiency. In addition, the number and size of vascular bundles in the culms and leaves were significantly increased in the OsCOMT-overexpressing plants, while decreased in the knockout plants, suggesting that OsCOMT plays a positive role in vascular development of rice. Further evidence indicated that OsCOMT-mediated vascular development might owe to the crosstalk between melatonin and cytokinin. More importantly, we found that OsCOMT is a positive regulator of grain yield, and overexpression of OsCOMT increase grain yield per plant even in a high-yield variety background, suggesting that OsCOMT can be used as an important target for enhancing rice yield. Our findings shed novel insights into melatonin-mediated leaf senescence and vascular development and provide a possible strategy for genetic improvement of rice grain yield.

A Novel Strategy Conjugating PD-L1 Polypeptide With Doxorubicin Alleviates Chemotherapeutic Resistance and Enhances Immune Response in Colon Cancer.

BACKGROUND: Modifying the structure of anti-tumor chemotherapy drug is of significance to enhance the specificity and efficacy of drug-delivery. A novel proteolysis resistant PD-L1-targeted peptide (PPA1) has been reported to bind to PD-L1 and disrupt the PD-1/PD-L1 interaction, thus appearing as an outstanding tumor-targeting modification of synergistic drug conjugate for effective anti-tumor treatment. However, the combination regimen of coupling PD-L1 polypeptide with chemotherapeutic drug in tumoricidal treatment has not been reported thus far. METHODS: We developed a novel synergistic strategy by conjugating PPA1 to doxorubicin (DOX) with a pH sensitive linker that can trigger the release of DOX near acidic tumor tissues. The binding affinity of PPA1-DOX with PD-L1 and the acid-sensitive cleavage of PPA1-DOX were investigated. A mouse xenograft model of colon cancer was used to evaluate the biodistribution, cytotoxicity and anti-tumor activity of PPA1-DOX. RESULTS: PPA1-DOX construct showed high binding affinity with PD-L1 in vitro and specifically enriched within tumor when administered in vivo. PPA1-DOX exhibited a significantly lower toxicity and a remarkably higher antitumor activity in vivo, as compared with free PPA1, random polypeptide-DOX conjugate, DOX, or 5-FU, respectively. Moreover, increased infiltration of both CD4+ and CD8+ T cells was found in tumors from PPA1-DOX treated mice. CONCLUSIONS: We describe here for the first time that the dual-functional conjugate PPA1-DOX, which consist of the PD-L1-targeted polypeptide that renders both the tumor-specific drug delivery and inhibitory PD-1/PD-L1 immune checkpoint inhibition, and a cytotoxic agent that is released and kills tumor cells once reaching tumor tissues, thus representing a promising therapeutic option for colon cancer with improved efficacy and reduced toxicity.

Dynamic prediction model of spontaneous combustion risk in goaf based on improved CRITIC-G2-TOPSIS method and its application.

Due to the problems related to the numerous factors affecting the spontaneous combustion of goaf coal, such as sudden, uncertain, and dynamic changes, and the fact that the weight of the indexes in the prediction model of the spontaneous combustion risk is difficult to determine, an improved Criteria Importance Through Inter-criteria Correlation (CRITIC) modified Technique for Order of Preference by Similarity to Ideal Solution G2-(TOPSIS) dynamic prediction model of goaf spontaneous combustion was developed. An optimal decision-making model was established by introducing the Euclidean distance function, and the function-driven type G2 weighting method was modified using the differential-driven type weighting method of the CRITIC. In addition, the comprehensive weights of each index were obtained. An update factor was introduced to obtain the dynamic weight, and the primary-secondary relationship of the risk factors affecting the spontaneous combustion of goaf was evaluated. Based on the G2 weighting method, which approximates the driving function principle of the ideal solution ranking method (TOPSIS), a G2-TOPSIS goaf spontaneous combustion risk assessment model was established. The degree of closeness was analyzed and the risk grade of the goaf spontaneous combustion was finally predicted. The sub-model was applied to the goaf of working face 1303 in the Jinniu Coal Mine. It was concluded that the air leakage duration was the dominant factor inducing the risk of the spontaneous combustion of the goaf. The risk grade of spontaneous combustion of the goaf is Class III, and the predicted results are consistent with the actual situation. The improved CRITIC-G2-TOPSIS dynamic model was demonstrated to be scientific in predicting the goaf spontaneous combustion risk, and these research results have important popularization and application value.

Distribution of spontaneous combustion three zones and optimization of nitrogen injection location in the goaf of a fully mechanized top coal caving face.

In order to effectively prevent and control spontaneous combustion of residual coal in the goaf and reduce the waste of nitrogen caused by setting the position of nitrogen injection, 1303 fully mechanized coal caving faces of the Jinniu Mine are studied. By deploying a bundle tube monitoring system in the inlet air side and return air side of the goaf, changes in gas concentration in the goaf are continuously monitored. In addition, the distribution area for spontaneous combustion three-zone in the goaf is divided into heat dissipation zone, oxidized spontaneous combustion zone, and suffocation zone. Simulations from the COMSOL Multiphysics 5.3 software provide insight based on the three zones division standard of spontaneous combustion in the goaf. The gradual deepening of the nitrogen injection position into the goaf affects the lower limit of the oxidized spontaneous combustion zone significantly, but the impact on the upper limit of the oxidized spontaneous combustion zone is not obvious and is negligible. With regard to the width of the oxidized spontaneous combustion zone, it initially decreases followed by a gradual increase. Numerical calculations suggest the optimal nitrogen injection position is 40 m from the roof cutting line, with an oxidized spontaneous combustion zone width of 28 m. Based on the simulation analysis results, nitrogen injection controlling measures have been adopted for spontaneous combustion of residual coal in the goaf of the 1303 fully mechanized coal caving faces, and coal self-ignition in the goaf has been successfully extinguished.

40-Hz Blue Light Changes Hippocampal Activation and Functional Connectivity Underlying Recognition Memory.

Research on light modulation has typically examined the wavelength, intensity, and exposure time of light, and measured rhythm, sleep, and cognitive ability to evaluate the regulatory effects of light variables on physiological and cognitive functions. Although the frequency of light is one of the main dimensions of light, few studies have attempted to manipulate it to test the effect on brain activation and performance. Recently, 40-Hz light stimulation has been proven to significantly alleviate deficits in gamma oscillation of the hippocampus caused by Alzheimer's disease. Although this oscillation is one of the key functional characteristics of performing memory tasks in healthy people, there is no evidence that 40-Hz blue light exposure can effectively regulate brain activities related to complex cognitive tasks. In the current study, we examined the difference in the effects of 40-Hz light or 0-Hz light exposure on brain activation and functional connectivity during a recognition memory task. Through joint augmentation of visual area activation, 40-Hz light enhanced brain areas mostly in the limbic system that are related to memory, such as the hippocampus and thalamus. Conversely, 0-Hz light enhanced brain areas mostly in the prefrontal cortex. Additionally, functional connection analysis, with the hippocampus as the seed point, showed that 40-Hz light enhanced connection with the superior parietal lobe and reduced the connection with the default network. These results indicate that light at a frequency of 40 Hz can change the activity and functional connection of memory-related core brain areas. They also indicate that in the use of light to regulate cognitive functions, its frequency characteristics merit attention.

Elevated atmospheric CO2 concentration triggers redistribution of nitrogen to promote tillering in rice.

Elevated atmospheric CO2 concentration (eCO2) often reduces nitrogen (N) content in rice plants and stimulates tillering. However, there is a general consensus that reduced N would constrain rice tillering. To resolve this contradiction, we investigated N distribution and transcriptomic changes in different rice plant organs after subjecting them to eCO2 and different N application rates. Our results showed that eCO2 significantly promoted rice tillers (by 0.6, 1.1, 1.7, and 2.1 tillers/plant at 0, 75, 150, and 225 kg N ha-1 N application rates, respectively) and more tillers were produced under higher N application rates, confirming that N availability constrained tillering in the early stages of growth. Although N content declined in the leaves (-11.0 to -20.7 mg g-1) and sheaths (-9.8 to -28.8 mg g-1) of rice plants exposed to eCO2, the N content of newly emerged tillers on plants exposed to eCO2 equaled or exceeded the N content of tillers produced under ambient CO2 conditions. Apparently, the redistribution of N within the plant per se was a critical adaptation strategy to the eCO2 condition. Transcriptomic analysis revealed that eCO2 induced less extensive alteration of gene expression than did N application. Most importantly, the expression levels of multiple N-related transporters and receptors such as nitrate transporter NRT2.3a/b and NRT1.1a/b were differentially regulated in leaf and shoot apical meristem, suggesting that multiple genes were involved in sensing the N signal and transporting N metabolites to adapt to eCO2. The redistribution of N in different organs could be a universal adaptation strategy of terrestrial plants to eCO2.

Physcion Protects Against Ethanol-Induced Liver Injury by Reprogramming of Circadian Clock.

The circadian clock plays a key role in our daily physiology and metabolism. Alcohol consumption disrupts the circadian rhythm of metabolic genes in the liver; however, the potential contribution of circadian clock modulation to alcoholic liver disease (ALD) is unknown. We identified a novel liver protective agent, physcion, which can alleviate fat accumulation and inflammation in ALD mice via reprogramming the hepatic circadian clock. The model of alcoholic hepatitis was established by intragastrically administering ethanol. In vitro, physcion was investigated by treating HepG2 cells with ethanol. The role of circadian clock in Physcion caused liver protection was tested by knocking down the core circadian gene Bmal1. Physcion application caused reduced lipogenesis and alleviated inflammation in alcohol-induced mice. In alcoholic hepatosteatosis models, physcion upregulated the core circadian genes. And the circadian misalignment triggered by ethanol was efficiently reversed by physcion. Physcion attenuated lipogenesis via reprogramming the circadian clock in HepG2 cells. Suppression of Bmal1 by RNA interference abolished the protective of physcion. In addition, Physcion binds to the active pocket of BMAL1 and promotes its expression. The study identified the novel liver protective effects of physcion on alcohol-induced liver injury, and modulation of the core circadian clock regulators contributes to ALD alleviation. More importantly, strategies targeting the circadian machinery, for example, Bmal1, may prove to be beneficial treatment options for this condition.

Non-invasive 40-Hz Light Flicker Ameliorates Alzheimer's-Associated Rhythm Disorder via Regulating Central Circadian Clock in Mice.

Alzheimer's disease (AD) patients often exhibit perturbed circadian rhythm with fragmented sleep before disease onset. This study was designed to evaluate the effect of a 40-Hz light flicker on circadian rhythm in an AD mouse model (APP/PS1). Locomotor rhythms recordings were conducted to examine the circadian clock rhythm in APP/PS1 mice. Molecular biology analyses, including western blot and real-time qPCR assays, were conducted to assess the changes in circadian locomotor output cycles kaput (CLOCK), brain and muscle arnt-like protein-1 (BMAL1), and period 2 (PER2). In addition to determining the direct effect of a 40-Hz light flicker on hypothalamic central clock, whole-cell voltage-clamp electrophysiology was employed to record individual neurons of suprachiasmatic nucleus (SCN) sections. The results reported herein demonstrate that a 40-Hz light flicker relieves circadian rhythm disorders in APP/PS1 mice and returns the expression levels of key players in the central circadian clock, including Clock, Bmal1, and Per2, to baseline. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in SCN neurons is significantly lower in APP/PS1 mice than in the control, and the amplitude of sIPSCs is decreased. Exposure to a 40-Hz light flicker significantly increases the sIPSC frequency in SCN neurons of APP/PS1 mice, with little effect on the amplitude. However, the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) are both unaffected by a 40-Hz light flicker. The data suggest that a 40-Hz light flicker can ameliorate AD-associated circadian rhythm disorders, presenting a new type of therapeutic treatment for rhythm disorders caused by AD.

Noninvasive 40-Hz Light Flicker Rescues Circadian Behavior and Abnormal Lipid Metabolism Induced by Acute Ethanol Exposure via Improving SIRT1 and the Circadian Clock in the Liver-Brain Axis.

Sirtuin 1 (SIRT1) is a protein deacetylase with important cellular functions, as it regulates numerous processes, including the circadian rhythm in peripheral tissues. Efforts are ongoing to reveal how Sirt1 can be used to treat diseases, such as alcoholic liver disease (ALD), Alzheimer's disease, and liver fibrosis. We have recently shown that noninvasive exposure to 40-Hz light flicker activates hypothalamic SIRT1 gene expression, thereby regulating the central circadian clock. This study investigated the effects of 40-Hz light flicker in a mouse model of ALD. RNA sequencing (RNA-seq) analysis was performed to explore the potential pathways affected by 40-Hz light flicker. We found that 40-Hz light flicker significantly decreased the acute ethanol-induced increases in serum alanine aminotransferase (ALT) and serum triglyceride (TG) levels and reduced fat-droplet accumulation in mouse livers. Additionally, 40-Hz light flicker significantly suppressed ethanol-induced increases in sterol regulatory element binding protein 1 (SREBP-1) and fatty acid synthase (Fasn) levels. Furthermore, the ethanol induced significant decreases in both Sirt1 levels and phosphorylation of adenosine monophosphate-activated protein kinase subunit (AMPKα), compared with those in the control group. Strikingly, pretreatment with 40-Hz light flicker ameliorated such ethanol-induced decreases in SIRT1 levels and AMPKα phosphorylation. In addition, ethanol-induced increases in levels of brain and muscle arnt-like protein-1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), and period 2 (PER2) were reversed by 40-Hz light flicker. RNA-seq analysis revealed significant differences in expression of genes related to the AMPK signalling. Moreover, ethanol consumption altered mRNA levels of Sirt1 and circadian genes in the suprachiasmatic nucleus (SCN), indicating that ethanol influenced central pacemaker genes; however, 40-Hz light flicker reversed these ethanol-induced changes. Taken together, our findings demonstrate that 40-Hz light flicker rapidly influence the SCN and exhibits inhibitory properties on hepatic lipogenesis, indicating that 40-Hz light flicker has therapeutic potential for preventing alcoholic liver steatosis.

Rotating magnetic field ameliorates experimental autoimmune encephalomyelitis by promoting T cell peripheral accumulation and regulating the balance of Treg and Th1/Th17.

Multiple sclerosis (MS) is an autoimmune disease characterized by T cell infiltration and demyelination of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a classical preclinical animal model of MS. In this study, we found that rotating magnetic field (RMF) treatment exerts potential preventive effects on the discovery of EAE, including reducing the severity of the disease and delaying the onset of the disease. The results indicated that RMF (0.2 T, 4 Hz) treatment increases the accumulation of CD4+ cells in the spleen and lymph nodes by downregulating the expression of CCL-2, CCL-3 and CCL-5, but has no significant effect on myelin oligodendrocyte glycoprotein (MOG) specific T cell responses. Simultaneously, RMF treatment adjusted the imbalance between regulatory T (Treg) cell and T helper 1 (Th1) cells or T helper 17 (Th17) cells by increasing the proportion of Treg cells and inhibiting the ratio of Th1 and Th17 cell subsets. These findings suggest that exposure to RMF may improve EAE disease by promoting CD4+ cell accumulation into peripheral lymphoid tissue, improving the imbalance between Treg and Th1/Th17 cells. Therefore, as a mild physical therapy approach, RMF, is likely to be a potential way to alter the development of EAE.

AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET-1-induced POAG.

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of ß-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.