Optimization clearing strategy for multi-region electricity-heat market considering shared energy storage and integrated demand response.

As a new type of energy storage, shared energy storage (SES) can help promote the consumption of renewable energy and reduce the energy cost of users. To this end, an optimization clearing strategy for a multi-region electricity-heat joint market is proposed with consideration of SES and integrated demand response (DR). Firstly, the concept of shared energy storage station (SESS) is proposed, its business operation model is analyzed and its advantages over traditional energy storage are compared. Secondly, to exploit the potential for user flexibility, an integrated DR model that includes shiftable, transferable, interruptible electricity and heat load is constructed. Then, a multi-region electricity-heat joint market clearing model is constructed considering SESS and integrated DR. Finally, a three-region electricity-heat joint market connecting the external power grid, gas grid, and the SESS is used as an example. A comparison is made between the configuration of independent energy storage in each region and the configuration of SESS, which concludes that the introduction of the SESS and integrated DR can reduce the energy cost of users and improve the utilization rate of the energy storage facilities.

Effects of Polyethylene Terephthalate Particle Size on the Performance of Engineered Cementitious Composites.

This study utilizes polyethylene terephthalate (PET) aggregate of different particle sizes (21 µm, 107 µm, and 244 µm) to replace natural aggregate in the preparation of PET-modified engineered cementitious composite (P-ECC). The impact of PET aggregate particle size on the performance of P-ECC is examined herein from micro to macro levels. The focus is on the influence patterns and mechanisms of P-ECC's workability, its basic mechanical properties, and its microstructure. Crack parameters are processed to quantitatively analyze crack development patterns. Using microscopic techniques, the interfacial transition zone (ITZ) between different aggregates and the cement matrix is compared, and the failure mechanism of P-ECC is analyzed. The results show that the incorporation of PET aggregate can improve P-ECC's workability and reduce its self-weight, but incorporation has a negative effect on compressive strength. Additionally, the particle size of PET aggregate significantly affects the uniaxial tensile performance of P-ECC. Compared to conventional ECC, the tensile strength of P-S (21 µm PET) increased the most markedly (18.1%), and the ultimate tensile strain of P-M (107 µm PET) increased the most markedly (66.0%), with both demonstrating good crack control and deformation energy dissipation capabilities. The uniaxial tensile performance of P-L (244 µm PET) was lower than that of the conventional ECC. Microscopic tests revealed that the increase in PET aggregate particle size enlarges the ITZ width and its surrounding pores. Appropriate pore enlargement is beneficial for enhancing tensile ductility, while excessive pores have a negative effect. The study results reveal the impact of PET aggregate particle size on the performance of P-ECC, providing new insights for the performance optimization of ECC.

Complementary therapy with Chinese aromatic herbs to promote awakening in a comatose patient: A case report.

RATIONALE: Traumatic brain injury frequently leads to prolonged coma, posing significant medical management challenges. Complementary therapies, including traditional Chinese herbal medicine, have been investigated as potential interventions in comatose patients. Chinese aromatic herbs, such as Borneolum (Bingpian), Moschus (Shexiang), and Acori tatarinowii rhizoma (Shichangpu), have long been believed to be "resuscitation with aromatics" based on traditional Chinese medicines theory. PATIENT CONCERNS: A 16-year-old male was admitted to the intensive rehabilitation unit for further treatment due to prolonged coma and frequent seizures following traumatic brain injury. DIAGNOSES: Western medicine diagnosed the patient as coma, diffuse axonal injury, and epilepsy. According to traditional Chinese medicine theory, the syndrome differentiation indicates a Yin-closed disease. INTERVENTIONS: According to the patient's condition, we use the Chinese aromatic herbs as a complementary therapy. OUTCOMES: Following a month-long administration, the patient's consciousness and electroencephalogram (EEG) background progressively improved. A 6-month follow-up demonstrated full arousal, though with ambulatory EEG revealing mild to moderate abnormality in the background. LESSONS: The addition of Chinese aromatic herbs appears to have a beneficial effect on the patient's consciousness and EEG background. This could be attributed to the herbs' inherent pharmacological properties, as well as their potential to enhance the permeability of the blood-brain barrier to other drugs. This makes them a promising option for complementary therapy.

Discovery of HPG1860, a Structurally Novel Nonbile Acid FXR Agonist Currently in Clinical Development for the Treatment of Nonalcoholic Steatohepatitis.

The farnesoid X receptor (FXR) is a ligand-activated nuclear receptor. Activation of FXR significantly impacts the expressions of the pivotal genes involved in bile acid metabolism, inflammation, fibrosis, and homeostasis of lipid and glucose, leading to considerable interests in developing FXR agonists for the treatment of nonalcoholic steatohepatitis (NASH) or other FXR-relevant diseases. Herein, we describe the design, optimization, and characterization of a series of N-methylene-piperazinyl derivatives as the nonbile acid FXR agonists. Particularly, compound 23 (HPG1860), a potent full FXR agonist, shows high selectivity, favorable ADME and pharmacokinetics profile, along with favorable in vivo activities demonstrated in both rodent PD model and HFD-CCl4 model and is currently in clinical development in patients with NASH in phase II.

Resveratrol alleviates postpartum depression-like behavior by activating autophagy via SIRT1 and inhibiting AKT/mTOR pathway.

BACKGROUND: Postpartum depression (PPD) causes maternal mortality, and has a high disability rate. In recent years, studies have suggested the Sirt1 gene to be involved in the pathogenesis of depression. Resveratrol (RSV), an activator of Sirt1, has been investigated in depressive behavior. However, its effect on PPD remains to be thoroughly elucidated. METHODS: We employed a mice model with bilateral oophorectomy combined with hormone-simulated pregnancy to assess postpartum depression-like behavior. The behavioral tests were performed 2 days after the withdrawal of estradiol benzoate. RSV was administered subcutaneously to the PPD model mice. Several behavioral tests were executed, including the open field test, forced swimming test, and tail suspension test. Western blot analyses and immunofluorescence staining were used to evaluate protein expression levels of SIRT1, autophagy markers, and the AKT/mTOR. RESULTS: Postpartum depressive-like behavior was triggered following the withdrawal of estradiol benzoate after hormone-stimulated-pregnancy. RSV improved postpartum depressive-like behavior of mice via its upregulation of the SIRT1 and autophagy markers, such as Beclin1, ATG5 and LC3B. Also, the downregulation of the p62 protein expression was observed. More importantly, we also detected the inhibition of phosphorylated AKT and mTOR in the hippocampus of postpartum depressive-like mice. CONCLUSION: RSV could alleviate postpartum depression-like behavior in mice by stimulating the SIRT1, induce autophagy and inhibit the AKT/ mTOR signaling pathway.

The identification of the key residues E829 and R845 involved in transient receptor potential melastatin 2 channel gating.

Transient receptor potential melastatin 2 (TRPM2), a non-selective cation channel, is involved in many physiological and pathological processes, including temperature sensing, synaptic plasticity regulation, and neurodegenerative diseases. However, the gating mechanism of TRPM2 channel is complex, which hinders its functional research. With the discovery of the Ca2+ binding site in the S2-S3 domain of TRPM2 channel, more and more attention has been drawn to the role of the transmembrane segments in channel gating. In this study, we focused on the D820-F867 segment around the S2 domain, and identified the key residues on it. Functional assays of the deletion mutants displayed that the deletions of D820-W835 and L836-P851 destroyed channel function totally, indicating the importance of these two segments. Sequence alignments on them found three polar and charged residues with high conservation (D820, E829, and R845). D820A, E829A, and R845A which removed the charge and the side chain of the residues were tested by 500 µM adenosine diphosphate-ribose (ADPR) or 50 mM Ca2+. E829A and R845A affected the characteristic of channel currents, while D820A behaved similarly to WT, indicating the participations of E829 and R845 in channel gating. The charge reversing mutants, E829K and R845D were then constructed and the electrophysiological tests showed that E829A and E829K made the channel lose function. Interestingly, R845A and R845D exhibited an inactivation process when using 500 µM ADPR, but activated normally by 50 mM Ca2+. Our data suggested that the negative charge at E829 took a vital part in channel activation, and R845 increased the stability of the Ca2+ combination in S2-S3 domain, thus guaranteeing the opening of TRPM2 channel. In summary, our identification of the key residues E829 and R845 in the transmembrane segments of TRPM2. By exploring the gating process of TRPM2 channel, our work helps us better understand the mechanism of TRPM2 as a potential biomarker in neurodegenerative diseases, and provides a new approach for the prediction, diagnosis, and prognosis of neurodegenerative diseases.

Preparation, identification, and molecular docking of novel elastase inhibitory peptide from walnut (Juglans regia L.) meal.

This study aimed to isolate bioactive peptides with elastase inhibitory activity from walnut meal via ultrasonic enzymatic hydrolysis. The optimal hydrolysis conditions of walnut meal protein hydrolysates (WMPHs) were obtained by response surface methodology (RSM), while a molecular weight of<3 kDa fraction was analyzed by LC-MS/MS, and 556 peptides were identified. PyRx virtual screening and Autodock Vina molecular docking revealed that the pentapeptide Phe-Phe-Val-Pro-Phe (FFVPF) could interact with elastase primarily through hydrophobic interactions, hydrogen bonds, and π-sulfur bonds, with a binding energy of -5.22 kcal/mol. The verification results of inhibitory activity showed that FFVPF had better elastase inhibitory activity, with IC50 values of 0.469 ± 0.01 mg/mL. Furthermore, FFVPF exhibited specific stability in the gastric environment. These findings suggest that the pentapeptide FFVPF from defatted walnut meal could serve as a potential source of elastase inhibitors in the food, medical, and cosmetics industries.

Enhanced Glial Reaction and Altered Neuronal Nitric Oxide Synthase are Implicated in Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) has a complex etiology, and its specific causal factors remain to be elucidated. Aberration of nitric oxide synthase (nNOS) and inflammation, together with astrocytic and microglial cells have been continually associated with several neurological disorders, including ADHD. Using spontaneously hypertensive rat (SHR), we investigated the changes in nNOS, inflammatory, microglial and astrocytic markers in the frontal cortex and hippocampus at three different ages: onset of hypertension stage (i.e., 6 weeks after birth of SHR), established hypertension stage (i.e., 12 weeks after birth of SHR) and senescent stage (i.e., 12 months after birth of SHR), and compared with its age-matched normotensive control, Wistar-Kyoto (WKY) rats. A significant upregulation of Iba-1 expression in the senescent stage of SHR was observed. Further, we observed an upregulated nNOS expression in both onset and established stages of SHR, and a downregulated nNOS in the senescent stage. Our study showed an age-related increment of astrogliosis in the cortex and hippocampi of aged SHR. On the basis of our results, alterations in the nNOS and Iba-1 expressions, as well as age-related astrogliosis, may contribute to ADHD pathogenesis.

Modulation of mean luminance improves binocular balance across spatial frequencies in amblyopia.

Amblyopia is a visual impairment that perturbs binocular balance at high spatial frequencies in favor of the fellow eye. Studies reveal that amblyopes who had been treated with monocular therapies still show imbalance. Binocular balance is achieved when both eyes' inputs are weighed equally. A reduced light can diminish the dimmed eye's weight in binocular combination. In this study, we examined if binocular balance across spatial frequencies could be improved by reducing the luminance of the fellow eye in adult amblyopes. By doing so, we relieved their binocular imbalance across spatial frequencies. Also, normal observers showed amblyopic binocular imbalance when the dominant eye's light level was dimmed. Therefore, reducing the luminance in the unaffected eye in amblyopia mitigated the binocular imbalance, whereas doing so in normal adults simulated the amblyopic imbalance across spatial frequencies.

Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice.

BACKGROUND: A blockage in a blood vessel can cause reduced blood flow to the brain, which eventually leads to the death of surrounding tissue. Several studies have attempted to develop an effective intervention to reverse this process and improve the health status of affected individuals. Due to its indirect effect on cellular functions and metabolism, the hypoxia-inducible factor (HIF-1α) protein has been proposed as a promising transcription factor in the treatment of stroke. PURPOSE: The current study aims to explore the relation between HIF-1 α and thymoquinone (TQ) in the attenuation of ischemic brain damage and the possible mechanism of this relation to reduce cell death. METHODS: For this purpose, dimethyloxallyl glycine (DMOG), 8 mg/kg, Acriflavine (ACF), 1.5 mg/kg, and both combined with TQ (5 mg/kg) were assessed. Male C57 mice were used to establish an ischemic stroke model by using endothelin-1 (ET-1) (400 pmole/µl) intra- cranial injection. The ultrastructure alterations of neuronal soma, axons, and mitochondria after stroke and treatment were well addressed. Besides, the expression levels of VEGF, HIF-1α, Nrf2, and HO-1 were evaluated. Meanwhile, apoptosis and autophagy-related proteins were also investigated. RESULTS: Treatment of ischemic stroke by TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis. Our study revealed that TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke. Further, we demonstrated that both TQ and DMOG effectively attenuate the organelle's damage following ischemic stroke, which was confirmed by the cryogenic transmission electron microscope. The synergistic effect of TQ and DMOG may lead to a chemo-modulation action in the autophagy process after stroke onset and this result is validated by the western blot and rt-qPCR techniques. CONCLUSION: Our finding revealed the potential role of TQ as a HIF-1 α activator to reduce cell death, modulate autophagy and decrease the infarct volume after ischemic stroke onset. The neuroprotective effect of TQ is achieved by decreasing the inflammation and increasing angiogenesis as well as neurogenesis via induction of the HIF-1α-VEGF/Nrf2-HO-1-TrkB-PI3K pathway.

Hydrophobically Associating Polymers Dissolved in Seawater for Enhanced Oil Recovery of Bohai Offshore Oilfields.

As compared to China's overall oil reserves, the reserve share of offshore oilfields is rather significant. However, offshore oilfield circumstances for enhanced oil recovery (EOR) include not just severe temperatures and salinity, but also restricted space on offshore platforms. This harsh oil production environment requires polymers with relatively strong salt resistance, solubility, thickening ability, rapid, superior injection capabilities, and anti-shearing ability. As a result, research into polymers with high viscosity and quick solubility is recognized as critical to meeting the criteria of polymer flooding in offshore oil reservoirs. For the above purposes, a novel hydrophobically associating polymer (HAP) was prepared to be used for polymer flooding of Bohai offshore oilfields. The synthetic procedure was free radical polymerization in aqueous solutions starting at 0 °C, using acrylamide (AM), acrylic acid (AA), 2-acrylamido-2-methylpropane sulfonic acid (AMPS), and poly(ethylene glycol) octadecyl methacrylate (POM) as comonomers. It was discovered that under ideal conditions, the molecular weight of HAP exceeds 2.1 × 107 g⋅mol-1. In a simulated reservoir environment, HAP has substantially greater solubility, thickening property, and salt resistance than conventional polyacrylamide (HPAM), with equivalent molecular weight. Finally, the injectivity and propagation of the two polymers in porous media were investigated. Compared with HPAM, which has a similar molecular weight, HAP solution with the concentration of 0.175% had a much better oil displacement effect in the porous medium, which can enhance oil recovery by 8.8%. These discoveries have the potential to pave the way for chemical EOR in offshore oilfields.

The comparative studies of complete chloroplast genomes in Actinidia (Actinidiaceae): novel insights into heterogenous variation, clpP gene annotation and phylogenetic relationships.

The genus Actinidia, also called kiwifruit, is characterized with abundant balanced nutritional metabolites, including exceptionally high vitamin C content. However, the traditional classification could not fully reflect the actual Actinidia species' relationships, which need further revision through more accurate approaches. Compared to the nuclear genome, the chloroplast genome has simple heredity characteristics, conserved genome structure and small size, suitable for deciphering complicated species' phylogenetic relationships. Here, the genome-wide comprehensive comparative analyses were performed over 29 independent chloroplast genomes' sequences derived from 25 Actinidia taxa. The average genome size is 156,673.38 bp, with an average 37.20% GC content. The long repeat sequences rather than SSRs (simple sequence repeats) in Actinidia were revealed to be the causal agent leading to the chloroplast genome size expansion. The clpP gene sequences with exon merge and intron deletion were annotated in all the 29 chloroplast genomes tested, which has been previously reported to be lost in Actinidia species. Comprehensive sequence analyses indicated the distinct variation at the clpP gene locus was Actinidiaceae-specific, emerging after the Actinidiaceae-other Ericales species divergence. Four highly divergent sequences (i.e., rps16 ~ trnQ-UUG, rps4 ~ trnT-UGU, petA ~ psbJ, and rps12 ~ psbB) evolved in the LSC (large single-copy) and SSC (small single-copy) regions embodying rps12 ~ psbB (including clpP gene and its up/downstream noncoding sequence) were identified as variation hot spots in Actinidia species. Based on either LSC region alone, combined sequences of LSC and SSC or the whole chloroplast genome sequences, three identical phylogenetic trees of the 25 Actinidia taxa with relatively improved resolution were reconstructed, consistently supporting the reticulate evolutionary lineage in Actinidia. Our findings could help to better understand the evolution characteristics of chloroplast genomes and phylogenetic relationships among Actinidia species.

A clinically convenient test to measure binocular balance across spatial frequency in amblyopia.

Amblyopia is a visual disorder that originates from the brain. It exhibits no pathology in the eye. Studies have shown that measuring both visual acuity and binocular balance for assessing amblyopia could be more helpful. However, tests that measure binocular balance are time-consuming, often exceeding 30 min. Their long test durations prevent them from being used in the clinic. For this reason, we have developed a quick (i.e., about 7 min) and precise tool that quantitatively measures binocular balance of patients with amblyopia. The new test can capture binocular imbalance that is typically exhibited at high spatial frequency in amblyopes. In addition, it has an excellent test-retest reliability and repeatability between two experimental sessions. We hope that our newly developed test can pave the road for physicians and researchers to better assess and diagnose amblyopia and other visual disorders that disrupt binocular balance beyond the laboratory.

The association of oxytocin with major depressive disorder: role of confounding effects of antidepressants.

Major depressive disorder is a genetic susceptible disease, and a psychiatric syndrome with a high rate of incidence and recurrence. Because of its complexity concerning etiology and pathogenesis, the cure rate of first-line antidepressants is low. In recent years, accumulative evidences revealed that oxytocin act as a physiological or pathological participant in a variety of complex neuropsychological activities, including major depressive disorder. Six electronic databases (Web of Science, PubMed, Scopus, Google Scholar, CNKI, and Wanfang) were employed for researching relevant publications. At last, 226 articles were extracted. The current review addresses the correlation of the oxytocin system and major depressive disorder. Besides, we summarize the mechanisms by which the oxytocin system exerts potential antidepressant effects, including regulating neuronal activity, influencing neuroplasticity and regeneration, altering neurotransmitter release, down regulating hypothalamic-pituitary-adrenal axis, anti-inflammatory, antioxidation, and genetic effects. Increasing evidence shows that oxytocin and its receptor gene may play a potential role in major depressive disorder. Future research should focus on the predictive ability of the oxytocin system as a biomarker, as well as its role in targeted prevention and early intervention of major depressive disorder.

Defects of parvalbumin-positive interneurons in the ventral dentate gyrus region are implicated depression-like behavior in mice.

Depression is an increasingly common but extremely serve mood disorder that remains poorly understood and inadequately treated. Fast-spiking parvalbumin-positive interneurons (PVIs), a subpopulation of GABAergic interneurons (GABA, g-aminobutyric acid), exhibit a widespread distribution throughout the hippocampus, and has been reported to play an important role in a variety of mental disorders. However, the relationship between depression and hippocampal PVIs remains unclear. Here in this present study, a series of experiments were conducted to clarify the potential relationship. Here, chronic unpredicted mild stress (CUMS) and Lipopolysaccharide (LPS) injection were introduced to induce depression-like behavior in mice, and led to a clear decline in PVIs numbers in the ventral hippocampal (vHPC), particularly in the ventral dentate gyrus (vDG) subfield. After a selectively removal of the PVIs in PV-ires-Cre::Ai14 mice, we confirmed that ablation of PVIs from the vDG induced depression-like behavior. Furthermore, we found that the removal of vDG-PVIs induced depression likely to be accounted for upregulation of neuroinflammation. These findings facilitate us better understand the role of hippocampal PVIs in depression.

Hypoxia Inducible Factor-1α Attenuates Ischemic Brain Damage by Modulating Inflammatory Response and Glial Activity.

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.

Therapeutic impact of thymoquninone to alleviate ischemic brain injury via Nrf2/HO-1 pathway.

Introduction: Reactive oxygen species (ROS)-mediated inflammation plays a crucial role in ischemic brain injury. Therefore, the activation of the nuclear erythroid 2 related protein and heme-oxygenase-1 (Nrf2/HO-1) pathway by thymoquinone (TQ) could ameliorate ischemic brain damage.Areas covered: The photo-thrombotic method was employed to assess the impact of TQ in attenuating ischemic brain damage in C57BL/6 J mice and thy1-YFP-16 transgenic mice. In vitro study of TQ efficiency to attenuate the oxygen-glucose deprivation/reoxygenation (OGD/R) induced cell death by fluorescence-activated cell sorting (FACs) analysis was also analyzed. The protein expression levels of Nrf2/HO-1, inflammatory, and apoptotic were evaluated by immunofluorescence and western blot techniques. Besides, mRNA expression level of inducible nitric oxide synthase (iNOS), proto-oncogene (c-MYC), proto-oncogene (c-FOS), 5-hydroxytryptamine receptors (5-HT), and autophagy-related 5 (Atg5) were evaluated by RT-qPCR. The dendritic spine density of YFP slices was determined by confocal microscope.Results: Our in vivo and in vitro results indicated that TQ significantly mitigates brain damage and motor dysfunction after ischemic stroke. These observations coincided with curtailed cell death, inflammation, oxidative stress, apoptosis, and autophagy. Most importantly, Nrf2/HO-1 signaling pathway activation by TQ was vital in the modulation of the above processes. Lastly, we found TQ to have minimal toxicity in liver tissue.Conclusion: Our study gives credence to TQ as a promising intervention therapy for cerebral ischemia that decreases inflammation, oxidative stress, and neuronal cell death via the Nrf2/HO-1 pathway, along with modulation of apoptotic and autophagic processes.

Binocular visual deficits at mid to high spatial frequency in treated amblyopes.

Amblyopia (lazy eye) is a neurodevelopmental disorder of vision with no ocular pathology. The loss of vision in the amblyopic eye is assumed to be the main deficit in amblyopia, which has resulted in visual acuity (VA) being the primary outcome measure for treatment. Here we used a binocular orientation combination task to quantitatively assess the binocular status by measuring the binocular balance. We set out to determine whether amblyopes who reach the acuity-based end point have a residual binocular imbalance. Our results suggest that even amblyopes who have regained normal acuity have residual binocular deficits over a wide range of spatial frequencies. A further control study suggests that these binocular deficits could not be explained by any residual contrast sensitivity deficits of the amblyopic eye. Consequently, amblyopia is not the primary problem and VA is not the appropriate end point measure.

Agomelatine Softens Depressive-Like Behavior through the Regulation of Autophagy and Apoptosis.

Depression is a common and disabling mental disorder with high recurrence rate. Searching for more effective treatments for depression is a long-standing primary objective in neuroscience. Agomelatine (AGO) was reported as an antidepressant with unique pharmacological effects. However, its effects and the underlying mechanism are still unclear. In this study, we sought to evaluate the antidepressant effects of AGO on the chronic restraint stress (CRS) mouse model and preliminarily investigate its effects on the gut microbial metabolites. The CRS model mice were established in 28 days with AGO (60 mg/kg/day, by oral) or fluoxetine (15 mg/kg/day, by oral) administration. The number of behavioral tests was conducted to evaluate the effect of AGO on depression-like behavior alleviation. Meanwhile, the expression of the BDNF/TrkB/pERK signaling pathway, apoptosis, autophagy, and inflammatory protein markers were assessed using western blot and immunofluorescence. Our findings show that AGO can attenuate the depressive-like behavior that significantly appeared in both sucrose preference and forced swimming tests. Additionally, a noticeable upregulation of autophagy including Beclin1 and LC3II, microglial activity marker Iba-1, and BDNF/TrkB/pERK signaling pathways are indicated. An obvious decreased expression of NF-κB, iNOS, and nNOS as well as apoptosis including Bax is observed in AGO administration mice. On the other hand, we found that AGO impacted the rebalancing of short-chain fatty acids (SCFAs) in mouse feces. Altogether, these findings suggest that AGO can exert antidepressant effects in a different molecular mechanism.

A Randomized Clinical Trial Comparing Eyetronix Flicker Glass and Patching for Treatment of Amblyopia in Children Reveals Similar Improvements in Vision.

PURPOSE: Recently, Eyetronix Flicker Glass (EFG) has been introduced as a novel treatment for amblyopia. It alternatively deprives the visual input of each eye rapidly (e.g., 7 Hz). However, whether it is comparable with standard patching therapy is unclear. In this randomized clinical trial, we evaluate the efficacy of an EFG therapy as treatment for amblyopia in children and compare it to the patching therapy. METHODS: We tested 31 children (aged 4-13 years) with amblyopia. They were assigned into one of the two treatment groups and were treated for 12 weeks. The first group was treated with EFG for 1 h/day (Flicker Group) and the latter with a standard patch (Patching Group) for 2 h/day. We designated changes from baseline in best-corrected visual acuity (BCVA) of the amblyopic eye as our primary outcome. Changes from baseline in other visual outcomes, such as contrast sensitivity, stereopsis, and fusional vergence range were measured as secondary outcome. RESULTS: BCVA improved significantly at 12 weeks relative to baseline in both the Flicker (0.13 ± 0.11 logMAR; mean ± SD) and Patching Groups (0.21 ± 0.14 logMAR). However, the improvements were not significantly different between groups (p = 0.13). Contrast sensitivity also significantly improved at 3 and 12 cycles/degree between baseline and 12 weeks in both groups (p's < 0.05). However, stereopsis and fusion range did not improve significantly in both groups. CONCLUSION: An EFG therapy and patching improved BCVA similarly for children with amblyopia at 12 weeks. Both therapies improved the contrast sensitivity at 3 and 12 cycles per degree (cpd); however, only patching improved the contrast sensitivity at 6 cpd. Both therapies did not benefit binocular visual functions (stereopsis and fusional vergence range). We believe that EFG can be an additional choice for therapy. CLINICAL TRIAL REGISTRATION: chictr.org number: ChiCTR2000034436.