GPNMB Modulates Autophagy to Enhance Functional Recovery After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) severely affects the quality of life and autonomy of patients, and effective treatments are currently lacking. Autophagy, an essential cellular metabolic process, plays a crucial role in neuroprotection and repair after SCI. Glycoprotein non-metastatic melanoma protein B (GPNMB) has been shown to promote neural regeneration and synapse reconstruction, potentially through the facilitation of autophagy. However, the specific role of GPNMB in autophagy after SCI is still unclear. In this study, we utilized the spinal cord transection method to establish SCI rats model and overexpressed GPNMB using adenoviral vectors. We assessed tissue damage using hematoxylin and eosin (H&E) and Nissl staining, and observed cell apoptosis using TUNEL staining. We evaluated the inflammatory response by measuring inflammatory factors using enzyme-linked immunosorbent assay (ELISA). In addition, we measured reactive oxygen species (ROS) levels using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and assessed oxidative stress levels by measuring malondialdehyde (MDA) and glutathione (GSH) using ELISA. To evaluate autophagy levels, we performed immunofluorescence staining for the autophagy marker Beclin-1 and conducted Western blot analysis for autophagy-related proteins. We also assessed limb recovery through functional evaluation. Meanwhile, we induced cell injury using lipopolysaccharide (LPS) and added an autophagy inhibitor to verify the impact of GPNMB on SCI through autophagy modulation. The results demonstrated that GPNMB alleviated the inflammatory response, reduced oxidative stress levels, inhibited cell apoptosis, and promoted autophagy following SCI. Inhibiting autophagy reversed the effects of GPNMB. These findings suggest that GPNMB promotes neural injury repair after SCI, potentially through attenuating the inflammatory response, reducing oxidative stress, and inhibiting cell apoptosis.

SRGN amplifies microglia-mediated neuroinflammation and exacerbates ischemic brain injury.

BACKGROUND: Microglia is the major contributor of post-stroke neuroinflammation cascade and the crucial cellular target for the treatment of ischemic stroke. Currently, the endogenous mechanism underlying microglial activation following ischemic stroke remains elusive. Serglycin (SRGN) is a proteoglycan expressed in immune cells. Up to now, the role of SRGN on microglial activation and ischemic stroke is largely unexplored. METHODS: Srgn knockout (KO), Cd44-KO and wild-type (WT) mice were subjected to middle cerebral artery occlusion (MCAO) to mimic ischemic stroke. Exogenous SRGN supplementation was achieved by stereotactic injection of recombinant mouse SRGN (rSRGN). Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurological functions were evaluated by the modified neurological severity score (mNSS) and grip strength. Microglial activation was detected by Iba1 immunostaining, morphological analysis and cytokines' production. Neuronal death was examined by MAP2 immunostaining and FJB staining. RESULTS: The expression of SRGN and its receptor CD44 was significantly elevated in the ischemic mouse brains, especially in microglia. In addition, lipopolysaccharide (LPS) induced SRGN upregulation in microglia in vitro. rSRGN worsened ischemic brain injury in mice and amplified post-stroke neuroinflammation, while gene knockout of Srgn exerted reverse impacts. rSRGN promoted microglial proinflammatory activation both in vivo and in vitro, whereas Srgn-deficiency alleviated microglia-mediated inflammatory response. Moreover, the genetic deletion of Cd44 partially rescued rSRGN-induced excessed neuroinflammation and ischemic brain injury in mice. Mechanistically, SRGN boosted the activation of NF-κB signal, and increased glycolysis in microglia. CONCLUSION: SRGN acts as a novel therapeutic target in microglia-boosted proinflammatory response following ischemic stroke.

Protective Effects of Hinokitiol on Neuronal Ferroptosis by Activating the Keap1/Nrf2/HO-1 Pathway in Traumatic Brain Injury.

In this study, we investigated the effects of hinokitiol, a small-molecule natural compound, against neuronal ferroptosis after traumatic brain injury (TBI). A controlled cortical impact (CCI) mouse model and excess glutamate-treated HT-22 cells were used to study the effects of hinokitiol on TBI. Hinokitiol mitigated TBI brain tissue lesions and significantly improved neurological function. Neuron loss and iron deposition were ameliorated after hinokitiol administration. Hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe2+ accumulation in HT-22. Mechanistically, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, hinokitiol is a potential therapeutic candidate for TBI by activating the Nrf2/Keap1/HO-1 signaling pathway.

The role of KDM4A-mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis.

Temozolomide (TMZ) resistance presents a significant challenge in the treatment of gliomas. Although lysine demethylase 4A (KDM4A) has been implicated in various cancer-related processes, its role in TMZ resistance remains unclear. This study aims to elucidate the contribution of KDM4A to TMZ resistance in glioma cells and its potential implications for glioma prognosis. We assessed the expression of KDM4A in glioma cells (T98G and U251MG) using qRT-PCR and Western blot assays. To explore the role of KDM4A in TMZ resistance, we transfected siRNA targeting KDM4A into drug-resistant glioma cells. Cell viability was assessed using the CCK-8 assay and the TMZ IC50 value was determined. ChIP assays were conducted to investigate KDM4A, H3K9me3, and H3K36me3 enrichment on the promoters of ROCK2 and HUWE1. Co-immunoprecipitation confirmed the interaction between HUWE1 and ROCK2, and we examined the levels of ROCK2 ubiquitination following MG132 treatment. Notably, T98G cells exhibited greater resistance to TMZ than U251MG cells, and KDM4A displayed high expression in T98G cells. Inhibiting KDM4A resulted in decreased cell viability and a reduction in the TMZ IC50 value. Mechanistically, KDM4A promoted ROCK2 transcription by modulating H3K9me3 levels. Moreover, disruption of the interaction between HUWE1 and ROCK2 led to reduced ROCK2 ubiquitination. Inhibition of HUWE1 or overexpression of ROCK2 counteracted the sensitization effect of si-KDM4A on TMZ responsiveness in T98G cells. Our findings highlight KDM4A's role in enhancing TMZ resistance in glioma cells by modulating ROCK2 and HUWE1 transcription and expression through H3K9me3 and H3K36me3 removal.

Hybrid Electrically Conductive Hydrogels with Local Nerve Growth Factor Release Facilitate Peripheral Nerve Regeneration.

It is challenging to treat peripheral nerve injury (PNI) clinically. As the gold standard for peripheral nerve repair, autologous nerve grafting remains a critical limitation, including tissue availability, donor-site morbidity, immune rejection, etc. Recently, conductive hydrogels (CHs) have shown potential applications in neural bioengineering due to their good conductivity, biocompatibility, and low immunogenicity. Herein, a hybrid electrically conductive hydrogel composed of acrylic acid derivatives, gelatin, and heparin with sustained nerve growth factor (NGF) release property was developed. The rat sciatic nerve injury (SNI) model (10 mm long segment defect) was used to investigate the efficacy of these hydrogel conduits in facilitating peripheral nerve repair. The results showed that the hydrogel conduits had excellent conductivity, mechanical properties, and biocompatibility. In addition, NGF immobilized in the hydrogel conduits had good sustained release characteristics. Finally, functional recovery and electrophysiological evaluations, together with histological analysis, indicated that the hydrogel conduits immobilizing NGF had superior effects on motor recovery, axon growth, and remyelination, thereby significantly accelerating the repairing of the sciatic nerve. This study demonstrated that hybrid electrically conductive hydrogels with local NGF release could be effectively used for PNI repair.

Ginsenoside Rb1 protects hippocampal neurons in depressed rats based on mitophagy-regulated astrocytic pyroptosis.

BACKGROUND: Astrocytes play a vital role in offering functional support for neurons, which are related to the pathogenic mechanism of depression. Ginsenoside Rb1 (GRb1) is demonstrated with antidepressant-like activities. PURPOSE: We aimed to investigate whether GRb1 can inhibit mitophagy-mediated astrocytic pyroptosis to protect neurons in depression. STUDY DESIGN: Model rats were subjected to chronic unpredictable mild stress (CUMS) for determining the in vivo antidepressant activity of GRb1. METHODS: The mitophagy-mediated antipyroptosis role of GRb1 was assessed in lipopolysaccharide (LPS) + ATP-stimulated astrocytes. The mechanism by which GRb1 protects synaptic plasticity was investigated using hippocampal neurons incubated in an astrocyte medium. The rat depressive-like behaviors were determined through sucrose preference, forced swimming, and the open-field tests. Escitalopram was used in the anti-depression control of GRb1. Cyclosporin A (CsA), a mitophagy inhibitor, and interleukin (IL)-1ß were used to reverse the role of GRb1 in mitophagy and pyroptosis, respectively. RESULTS: GRb1 inhibited LPS-induced inflammation and activation in the astrocytes and repressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Also, GRb1 repressed LPS + ATP-promoted astrocytic pyroptosis. During GRb1 treatment, the activation of mitophagy with a decrease in ROS was observed in LPS + ATPs-stimulated astrocytes. CsA enhanced GRb1-decreased ROS and promoted astrocytic pyroptosis. The GRb1-treated astrocyte medium suppressed neuron death and increased neuron viability and synaptic density. Escitalopram and GRb1 improved the depressive-like behaviors of the rats. GRb1 activated mitophagy and inhibited astrocytic activation and pyroptosis in rats with depression. It also reduced impairments in synaptic structures and increased synaptic density in depressive-like rats. IL-1ß increased astrocytic pyroptosis and reversed GRb1-enhanced synaptic plasticity in the rats exposed to CUMS. There were no statistical changes in depressive-like behaviors between GRb1 and Escitalopram groups. CONCLUSION: GRb1 modulates mitophagy and the NF-κB pathway to inhibit astrocytic pyroptosis, thereby maintaining neurological homeostasis by repressing inflammation and enhancing synaptic plasticity.

FOXM1 maintains fatty acid homoeostasis through the SET7-H3K4me1-FASN axis.

Reprogramming of metabolic genes and subsequent alterations in metabolic phenotypes occur widely in malignant tumours, including glioblastoma (GBM). FOXM1 is a potent transcription factor that plays an oncogenic role by regulating the expression of many genes. As a SET domain containing protein, SET7 is a protein lysine methyltransferase which monomethylates histone proteins and other proteins. The epigenetic modification of histones regulates gene expressions by epigenetically modifying promoters of DNAs and inter vening in tumor development. Activation of FASN increased de novo fatty acid (FA) synthesis, a hallmark of cancer cells. Here, we report that FOXM1 may directly promote the transcription of SET7 and activate SET7-H3K4me1-FASN axis, which results in the maintenance of de novo FA synthesis.

How Much Is Enough? A Study on Diffusion Times in Score-Based Generative Models.

Score-based diffusion models are a class of generative models whose dynamics is described by stochastic differential equations that map noise into data. While recent works have started to lay down a theoretical foundation for these models, a detailed understanding of the role of the diffusion time T is still lacking. Current best practice advocates for a large T to ensure that the forward dynamics brings the diffusion sufficiently close to a known and simple noise distribution; however, a smaller value of T should be preferred for a better approximation of the score-matching objective and higher computational efficiency. Starting from a variational interpretation of diffusion models, in this work we quantify this trade-off and suggest a new method to improve quality and efficiency of both training and sampling, by adopting smaller diffusion times. Indeed, we show how an auxiliary model can be used to bridge the gap between the ideal and the simulated forward dynamics, followed by a standard reverse diffusion process. Empirical results support our analysis; for image data, our method is competitive with regard to the state of the art, according to standard sample quality metrics and log-likelihood.

Operative treatment of cystic prolactinomas: a retrospective study.

BACKGROUND: The optimal therapeutic approach for cystic prolactinomas remains unclear. This study aimed to evaluate the remission rates of prolactinoma patients after surgical treatment and the risk factors affecting postoperative remission in cystic prolactinoma patients. METHODS: The clinical data were retrospectively compiled from 141 patients with prolactinomas (including 41 cases of cystic prolactinomas, 21 cases of solid microprolactinomas and 79 cases of solid macroprolactinomas) who underwent transsphenoidal surgery (TSS) between April 2013 and October 2021 at the First Affiliated Hospital of Sun Yat-sen University. RESULTS: Early postoperative remission was achieved in 65.83% (n = 27/41) of cystic prolactinomas, 80.95% (n = 17/21) of solid microprolactinomas and 40.51% (n = 32/79) of solid macroprolactinomas. The mean length of follow up in all patients was 43.95 ± 2.33 months (range: 6-105 months). The follow-up remission rates were 58.54%, 71.43% and 44.30% in cystic, solid micro- and solid macroprolactinomas, respectively. For cystic prolactinomas, the early postoperative remission rates in the patients with preoperative dopamine agonists (DA) treatment were significantly higher than those without preoperative DA treatment (p = 0.033), but the difference in the follow-up remission rates between these two groups was not significant (p = 0.209). Multivariate stepwise logistic regression analysis indicated that tumor size and preoperative prolactin (PRL) levels < 200 ng/ml were independent predictors for early postoperative remission in cystic prolactinomas. CONCLUSION: For cystic prolactinomas, tumor size and preoperative PRL levels were independent predictors of early postoperative remission. Preoperative DA therapy combined with TSS may be more beneficial to cystic prolactinoma patients.

Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia.

BACKGROUND: Chronic cerebral ischemia induces white matter injury (WMI) contributing to cognitive decline. Both astrocytes and microglia play vital roles in the demyelination and remyelination processes, but the underlying mechanism remains unclear. This study aimed to explore the influence of the chemokine CXCL5 on WMI and cognitive decline in chronic cerebral ischemia and the underlying mechanism. METHODS: Bilateral carotid artery stenosis (BCAS) model was constructed to mimic chronic cerebral ischemia in 7-10 weeks old male mice. Astrocytic Cxcl5 conditional knockout (cKO) mice were constructed and mice with Cxcl5 overexpressing in astrocytes were generated by stereotactic injection of adeno-associated virus (AAV). WMI was evaluated by magnetic resonance imaging (MRI), electron microscopy, histological staining and western blotting. Cognitive function was examined by a series of neurobehavioral tests. The proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), phagocytosis of microglia were analyzed via immunofluorescence staining, western blotting or flow cytometry. RESULTS: CXCL5 was significantly elevated in the corpus callosum (CC) and serum in BCAS model, mainly expressed in astrocytes, and Cxcl5 cKO mice displayed improved WMI and cognitive performance. Recombinant CXCL5 (rCXCL5) had no direct effect on the proliferation and differentiation of OPCs in vitro. Astrocytic specific Cxcl5 overexpression aggravated WMI and cognitive decline induced by chronic cerebral ischemia, while microglia depletion counteracted this effect. Recombinant CXCL5 remarkably hindered microglial phagocytosis of myelin debris, which was rescued by inhibition of CXCL5 receptor C-X-C motif chemokine receptor 2 (CXCR2). CONCLUSION: Our study revealed that astrocyte-derived CXCL5 aggravated WMI and cognitive decline by inhibiting microglial phagocytosis of myelin debris, suggesting a novel astrocyte-microglia circuit mediated by CXCL5-CXCR2 signaling in chronic cerebral ischemia.

MYPT1SMKO Mice Function as a Novel Spontaneous Age- and Hypertension-Dependent Animal Model of CSVD.

Cerebral small vessel disease (CSVD) is the most common progressive vascular disease that causes vascular dementia. Aging and hypertension are major contributors to CSVD, but the pathophysiological mechanism remains unclear, mainly due to the lack of an ideal animal model. Our previous study revealed that vascular smooth muscle cell (VSMC)-specific myosin phosphatase target subunit 1 (MYPT1) knockout (MYPT1SMKO) leads to constant hypertension, prompting us to explore whether hypertensive MYPT1SMKO mice can be considered a novel CSVD animal model. Here, we found that MYPT1SMKO mice displayed age-dependent CSVD-like neurobehaviors, including decreased motion speed, anxiety, and cognitive decline. MYPT1SMKO mice exhibited remarkable white matter injury compared with control mice, as shown by the more prominent loss of myelin at 12 months of age. Additionally, MYPT1SMKO mice were found to exhibit CSVD-like small vessel impairment, including intravascular hyalinization, perivascular space enlargement, and microbleed and blood-brain barrier (BBB) disruption. Last, our results revealed that the brain of MYPT1SMKO mice was characterized by an exacerbated inflammatory microenvironment, which is similar to patients with CSVD. In light of the above structural and functional phenotypes that closely mimic the conditions of human CSVD, we suggest that MYPT1SMKO mice are a novel age- and hypertension-dependent animal model of CSVD.

Fiber Density and Structural Brain Connectome in Glioblastoma Are Correlated With Glioma Cell Infiltration.

BACKGROUND: Glioblastoma (GBM) preferred to infiltrate into white matter (WM) beyond the recognizable tumor margin. OBJECTIVE: To investigate whether fiber density (FD) and structural brain connectome can provide meaningful information about WM destruction and glioma cell infiltration. METHODS: GBM cases were collected based on inclusion criteria, and baseline information and preoperative MRI results were obtained. GBM lesions were automatically segmented into necrosis, contrast-enhanced tumor, and edema areas. We obtained the FD map to compute the FD and lnFD values in each subarea and reconstructed the structural brain connectome to obtain the topological metrics in each subarea. We also divided the edema area into a nonenhanced tumor (NET) area and a normal WM area based on the contralesional lnFD value in the edema area, and computed the NET ratio. RESULTS: Twenty-five GBM cases were included in this retrospective study. The FD/lnFD value and topological metrics (aCp, aLp, aEg, aEloc, and ar) were significantly correlated with GBM subareas, which represented the extent of WM destruction and glioma cell infiltration. The FD/lnFD values and topological parameters were correlated with the NET ratio. In particular, the lnFD value in the edema area was correlated with the NET ratio (coefficient, 0.92). Therefore, a larger lnFD value indicates more severe glioma infiltration in the edema area and suggests an extended resection for better clinical outcomes. CONCLUSION: The FD and structural brain connectome in this study provide a new insight into glioma infiltration and a different consideration of their clinical application in neuro-oncology.

Morinda officinalis oligosaccharides mitigate depression-like behaviors in hypertension rats by regulating Mfn2-mediated mitophagy.

OBJECTIVE: Patients with hypertension have a risk of depression. Morinda officinalis oligosaccharides (MOOs) have anti-depressant properties. In this study, we aimed to determine whether MOOs can improve the symptoms of depression in individuals with hypertension. METHODS: Dahl salt-sensitive rats fed with a high-salt diet were stimulated by chronic unpredictable mild stress to mimic hypertension with depression. Primary astrocytes and neurons were isolated from these rats. Astrocytes underwent LPS stimulation to simulate the inflammatory astrocytes during depression. MOOs were administrated at 0.1 mg/g/day in vivo and 1.25, 2.5, and 5 mg/mL in vitro. Mitophagy was inhibited using 5 mM 3-methyladenine (3-MA). Astrocyte-mediated neurotoxicity was detected by co-culturing astrocytes and neurons. RESULTS: MOOs decreased systolic pressure, diastolic pressure, and mean arterial pressure, thereby improving depression-like behavior, including behavioral despair, lack of enthusiasm, and loss of pleasure during hypertension with depression. Furthermore, MOOs inhibited inflammation, astrocytic dysfunction, and mitochondrial damage in the brain. Then, MOOs promoted autophagosome and lysosome enriched in mitochondria in LPS-stimulated astrocytes. MOOs suppressed mitochondrial damage and the release of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß in astrocytes undergoing LPS stimulation. Importantly, MOOs rescued the impaired neurons co-cultured with astrocytes. The effects of MOOs on LPS-stimulated astrocytes were reversed by 3-MA. Finally, MOOs upregulated LPS-downregulated Mfn2 expression in astrocytes. Mfn2 inhibition partly reversed the effects of MOOs on hypertension with depression. Intriguingly, Mfn2 suppression activated PI3K/Akt/mTOR pathway during MOOs treatment. CONCLUSIONS: Astrocytes develop neuroinflammation in response to mitochondrial damage during hypertension with depression. MOOs upregulated Mfn2 expression to activate the PI3K/Akt/mTOR pathway-mediated mitophagy, thereby removing impaired mitochondria in astrocytes. HIGHLIGHTS: 1. MOOs have anti-hypertensive and anti-depressive properties. 2. MOOs inhibit inflammation and injury in astrocytes during hypertension with depression. 3. MOOs induce mitophagy activation in inflammatory astrocytes with mitochondrial damage. 4. MOOs upregulate Mfn2 expression in astrocytes. 5. Mfn2 activates mitophagy to resist mitochondrial damage in astrocytes.

Transsphenoidal surgery for prolactinomas in male patients: a retrospective study.

Male patients with prolactinomas usually present with typical hyperprolactinemia symptoms, including sexual dysfunction and infertility. However, clinical factors related to sexual dysfunction and surgical outcomes in these patients remain unclear. This study aimed to investigate the outcomes of male patients with prolactinomas after transsphenoidal surgery and the risk factors affecting sexual dysfunction. This study was conducted on 58 male patients who underwent transsphenoidal surgery for prolactinomas between May 2014 and December 2020 at the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. We evaluated the sexual function of patients before and after surgery through International Index of Erectile Function-5 scores, libido, and frequency of morning erection. Of the 58 patients, 48 (82.8%) patients had sexual intercourse preoperatively. Among those 48 patients, 41 (85.4%) patients presented with erectile dysfunction. The preoperative International Index of Erectile Function-5 scores in patients with macroprolactinomas were significantly higher than those in patients with giant prolactinomas (17.63 ± 0.91 vs 13.28 ± 1.43; P = 0.01). Postoperatively, the incidence of erectile dysfunction was 47.9%, which was significantly lower than that preoperatively (85.4%; P = 0.01). Twenty-eight (68.3%) patients demonstrated an improvement in erectile dysfunction. Tumor size and invasiveness were significantly correlated with the improvement of erectile dysfunction. Preoperative testosterone <2.3 ng ml-1 was an independent predictor of improvement in erectile dysfunction. In conclusion, our results indicated that tumor size and invasiveness were important factors affecting the improvement of sexual dysfunction in male patients with prolactinoma. The preoperative testosterone level was an independent predictor related to the improvement of erectile dysfunction.

Antidepression of Xingpijieyu formula targets gut microbiota derived from depressive disorder.

OBJECTIVE: This investigation aims to determine the antidepressant role of Xingpijieyu formula (XPJYF) mediated via gut microbiota (GM)-brain axis. METHODS: We collected fecal microbiota from patients with depressive disorder (DD) and cultured microbiota in vitro. Some of microbiota were transplanted into germ-free rats with the intragastric administration of XPJYF grain at the dose of 1.533 g/kg/day. The behaviors were studied by forced swimming test, open field test, sucrose preference test, and body weight. Products of hypothalamus-pituitary-adrenocortical (HPA) axis, neurotransmitter, and serum cytokines were investigated by enzyme linked immunosorbent assay. Glial fibrillary acidic protein (GFAP), a biomarker of astrocyte, was quantified using immunofluorescence. Microbiota culturing in vitro after XPJYF treatment was analyze by 16 s RNA sequencing technology. We used lipopolysaccharide (LPS) to mimic activated rat primary astrocyte in vitro. Brain-derived neurotrophic factor (BDNF), cytokines, and oxidative stress factors were determined by western blotting, and glycometabolism in astrocyte was investigated by 2-deoxy-D-glucose (2-DG) uptake, adenosine triphosphate (ATP), and glucose-1-phosphate (G1P) kits. RESULTS: Microbiota composition during 8 mg/ml of XPJYF (H12-8) for 12 h showed the more consistency. Lactococcus is enriched in DD-derived microbiota composition, and Biffdobacterium and Lactobacillus in H12-8 group. GLUCOSE1PMETAB-PWY and PWY-7328 of which biofunctions were dominantly encoded by Biffdobacterium were the top two of altered pathways. XPJYF improved behaviors and repressed astrocyte activation in depression rats. XPJYF elevated 2-DG uptake, ATP, glucose-1-phosphate, and brain-derived neurotrophic factor (BDNF), and inhibited cytokines and oxidative stress in LPS-induced astrocyte. CONCLUSION: XPJYF treatment targets inflammation, activation, and glycometabolim in astrocyte via gut microbiota modulation, thereby improve animal behaviors, HPA axis dysfunction, and neurotransmitter synthesis in depression rats.

Circ-E-Cad encodes a protein that promotes the proliferation and migration of gastric cancer via the TGF-ß/Smad/C-E-Cad/PI3K/AKT pathway.

Accumulating studies indicate that circular RNAs (circRNAs) play critical roles in cancer progression. Most of them have been reported to act as microRNA sponges or interact with RNA-binding proteins; however, their full range of functions remains largely unclear. Recently, an increasing number of circRNAs have been found to encode proteins. C-E-Cad, a protein encoded by circular E-cadherin (circ-E-Cad), has been shown to have a great influence in the progression of glioblastoma, but its specific role in gastric cancer (GC) is unclear. Here, we found that both circ-E-Cad and C-E-Cad were upregulated in GC cell lines and GC tissues compared with a human gastric epithelial cell line (GES-1) and normal tissues. Knockdown of circ-E-Cad suppressed GC cell line proliferation and metastasis in vitro and in vivo, whereas overexpression of C-E-Cad had the opposite effects. Immunoblotting revealed that C-E-Cad exerted tumor-promoting functions by regulating the PI3K/AKT pathway. A rescue experiment showed that C-E-Cad but not circ-E-Cad was the executor of protumor biological functions. In addition, we demonstrated that the C-E-Cad expression level could have been increased by the TGF-ß/Smad pathway. In summary, our results indicated that the TGF-ß/Smad pathway could increase the expression of C-E-Cad to regulate GC cell proliferation, migration, and epithelial-mesenchymal transition by affecting PI3K/AKT signaling.

Engineering Crystal Orientation of Cathode for Advanced Lithium-Ion Batteries: A Minireview.

Engineering crystal orientation has attracted widespread attention since it is related to the cyclability and rate performance of cathode materials for lithium-ion batteries (LIBs). Regulating the crystal directional growth with optimal exposed crystal facets is an effective strategy to improve the performance of cathode materials, but still lacks sufficient attention in research field. Herein, we briefly introduce the characterization techniques and identification methods for crystal facets, then summarize and illuminate the major methods for regulating crystal orientation and their internal mechanism. Furthermore, the optimization strategies for layered-, spinel-, and olivine-structure cathodes are discussed based on the characteristic of crystal structure, and the relationship between exposure of special crystal facets and lithium storage performance is deeply analyzed, which could guide the rational design of cathodes for LIBs.

Shugan granule contributes to the improvement of depression-like behaviors in chronic restraint stress-stimulated rats by altering gut microbiota.

AIM: The investigation aims to evaluate the potential effect of Shugan Granule (SGKL) on the gut, brain, and behaviors in rats exposed to chronic restraint stress (CRS). METHODS: The fecal microbiota and metabolite changes were studied in rats exposed to CRS and treated with SGKL (0.1 mg/kg/day). Depressive behaviors of these rats were determined through an open-field experiment, forced swimming test, sucrose preference, and weighing. Moreover, LPS-stimulated microglia and CRS-stimulated rats were treated with SGKL to investigate the regulation between SGKL and the PI3K/Akt/pathway, which is inhibited by LY294002, a PI3K inhibitor. RESULTS: (i) SGKL improved the altered behaviors in CRS-stimulated rats; (ii) SGKL ameliorated the CRS-induced neuronal degeneration and tangled nerve fiber and also contributed to the recovery of intestinal barrier injury in these rats; (iii) SGKL inhibited the hippocampus elevations of TNF-α, IL-1ß, and IL-6 in response to CRS modeling; (iv) based on the principal coordinates analysis (PCoA), SGKL altered α-diversity indices and shifted ß-diversity in CRS-stimulated rats; (v) at the genus level, SGKL decreased the CRS-enhanced abundance of Bacteroides; (vi) Butyricimonas and Candidatus Arthromitus were enriched in SGKL-treated rats; (vii) altered gut microbiota and metabolites were correlated with behaviors, inflammation, and PI3K/Akt/mTOR pathway; (viii) SGKL increased the LPS-decreased phosphorylation of the PI3K/Akt/mTOR pathway in microglia and inhibited the LPS-induced microglial activation; (ix) PI3K/Akt/mTOR pathway inactivation reversed the SGKL effects in CRS rats. CONCLUSION: SGKL targets the PI3K/Akt/mTOR pathway by altering gut microbiota and metabolites, which ameliorates altered behavior and inflammation in the hippocampus.

Psychological Health and Sleep Quality of Medical Graduates During the Second Wave of COVID-19 Pandemic in Post-epidemic Era.

Recently, a COVID-19 virus variant spread rapidly in Guangzhou, China, causing public panic. This study aimed to understand the psychological and sleep-related consequences of the secondary outbreak of the pandemic on medical students. In this cross-sectional survey-based study, participants anonymously completed structured questionnaires online from June 8-22, 2021. We collected participants' demographic and general information. Anxiety, depression, and sleep quality were measured using the Zung Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI), respectively. Protective factors were assessed using the Coping Style Questionnaire (CSQ). Uni- and multivariate logistic regression analyses were performed examining factors associated with mental health and sleep quality problems. During the second wave of the pandemic in local outbreak areas in Guangzhou, China, more than one-third of medical students' mental health and sleep quality were affected. The prevalence of anxiety, depression, and poor sleep quality were 27.54%, 27.58%, and 18.19%, respectively. Students belonging to the Class of 2019, aged over 29 years, those with siblings, and those whose hometowns were in other provinces were more prone to the three health problems. Factors associated with an increased risk of mental health problems were vaccination status (adjusted odds ratio 1.603-1.839) and diet status (adjusted odds ratio 1.62-1.929). Positive coping styles served as protective factors (p < 0.05). We discovered that completed vaccination status, good diet, and positive coping styles were related to good mental health and sleep quality.