Trelagliptin Mitigates Macrophage Infiltration by Preventing the Breakdown of the Blood-Brain Barrier in the Brain of Middle Cerebral Artery Occlusion Mice.

Stroke is a significant cardiovascular disease that influences the health of human beings all over the world, especially the elderly population. It is reported that the blood-brain barrier (BBB) can be easily destroyed by stroke, which is one of the main factors responsible for macrophage infiltration and central nervous inflammation. Here, we report the protective effects of Trelagliptin against BBB injury and macrophage infiltration. Our results indicate that the infraction volume, the neurological score, and macrophage infiltration staining with CD68 were increased in middle cerebral artery occlusion (MCAO) mice but significantly reversed by treatment with Trelagliptin. Additionally, Trelagliptin reduced the permeability of the BBB by increasing the expression of the tight junction zonula occludens protein-1 (ZO-1) in the cerebral cortex. In an in vitro hypoxia model of endothelial cells, the increased migration of macrophages, enlarged permeability of endothelial monolayer, downregulation of ZO-1, and elevated expression level of CXCL1 by hypoxic conditions were all reversed by treatment with Trelagliptin in a dose-dependent manner. Our results demonstrate that Trelagliptin might mitigate macrophage infiltration by preventing the breakdown of the blood-brain barrier in the brains of MCAO mice.

Combination of probiotics with different functions alleviate DSS-induced colitis by regulating intestinal microbiota, IL-10, and barrier function.

The potential of probiotics for treating ulcerative colitis (UC) has attracted increasing attention. However, more studies are still needed to guide physicians on the proper selection and use of probiotics. Here, we propose that combination of multiple probiotics with different functions can reduce intestinal inflammation. In this study, the effects of probiotics (Lactobacillus reuteri, Bacillus coagulans, Bifidobacterium longum, and Clostridium butyricum) on the physiology and histopathology of colon were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. The combined species, as well as the species individually, were tested and compared with sulfasalazine (SASP) and two Chinese herbal therapies. Results show that the functions of the four probiotic strains were different in regulating intestinal immunity and barrier function. The four-species probiotic cocktail was more effective than the species individually and anti-inflammatory drugs in repairing the dysbiosis of mucosal microbial ecology and reducing intestinal inflammation. The multi-strain probiotic mixture increased the proportion of beneficial bacteria and decreased the proportion of pro-inflammatory bacteria in the colonic mucosa. In addition, probiotic mixture significantly enhanced the expression of IL-10 and intestinal barrier function. These results suggest that a combination of multiple probiotics with different functions has synergistic effects and can restore the balance of interactions between microorganisms and immunological niches.

Simvastatin decreases the silver resistance of E. faecalis through compromising the entrapping function of extracellular polymeric substances against silver.

Enterococcus faecalis (E. faecalis) is a Gram-positive bacterium closely related to many refractory infections of human and shows the resistant ability against the antibacterial effects of silver. Simvastatin is a semisynthetic compound derived from lovastatin and a hydroxymethyl glutaryl coenzyme A(HMG-COA) reductase inhibitor showing certain inhibitive effects on bacteria. The main purpose of this study was to establish and characterize the Ag+/silver nanoparticles (AgNPs)-resistant E. faecalis, and further evaluate the function of extracellular polymeric substances (EPS) in the silver resistance and the effect of simvastatin on the silver-resistance of E. faecalis. The results showed that the established silver-resistant E. faecalis had strong resistance against both Ag+ and AgNPs and simvastatin could decrease the silver-resistance of both original and Ag+/AgNPs-resistant E. faecalis. The Transmission electron microscopy (TEM), High-angle annular dark-field (HAADF) and mapping images showed that the silver ions or particles aggregated and confined in the EPS on surface areas of the cell membrane when the silver-resistant E. faecalis were incubated with Ag+ or AgNPs. When the simvastatin was added, the silver element was not confined in the EPS and entered the bacteria. These findings may indicate that the silver resistance of E. faecalis was derived from the entrapping function of EPS, but simvastatin could compromise the function of EPS to decrease the silver resistant ability of E. faecalis.

Extraction and Research of Crop Feature Points Based on Computer Vision.

Based on computer vision technology, this paper proposes a method for identifying and locating crops in order to successfully capture crops in the process of automatic crop picking. This method innovatively combines the YOLOv3 algorithm under the DarkNet framework with the point cloud image coordinate matching method, and can achieve the goal of this paper very well. Firstly, RGB (RGB is the color representing the three channels of red, green and blue) images and depth images are obtained by using the Kinect v2 depth camera. Secondly, the YOLOv3 algorithm is used to identify the various types of target crops in the RGB images, and the feature points of the target crops are determined. Finally, the 3D coordinates of the feature points are displayed on the point cloud images. Compared with other methods, this method of crop identification has high accuracy and small positioning error, which lays a good foundation for the subsequent harvesting of crops using mechanical arms. In summary, the method used in this paper can be considered effective.

TiO2 nanoparticle-induced neurotoxicity may be involved in dysfunction of glutamate metabolism and its receptor expression in mice.

Titanium dioxide nanoparticles (TiO2 NPs) have been used in environmental management, food, medicine, and industry. But TiO2 NPs have been demonstrated to cross the blood-brain barrier and store up in the brain organization, leading to glutamate-mediated neurotoxicity. However, the neurotoxicity in the brain is not well understood. In this study, mice were exposed to 1.25, 2.5, or 5 mg/kg body weight TiO2 NPs for 9 months, and the glutamate-glutamine cyclic pathway and expressions of glutamate receptors associated with the hippocampal neurotoxicity were investigated. Our findings showed elevations of glutamate release and phosphate-activated glutaminase activity, and reductions in glutamine and glutamine synthetase in the hippocampus following exposure to TiO2 NPs. Furthermore, TiO2 NPs significantly inhibited the expression of N-methyl-d-aspartate receptor subunits (including NR1, NR2A, and NR2B) and metabotropic glutamate receptor 2 in mouse hippocampus. These findings suggest that the imbalance of glutamate metabolism triggered inhibitions of glutamate receptor expression in the TiO2 NP-exposed hippocampus. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 655-662, 2016.

Potentiometric sensing utilizing paper-based microfluidic sampling.

A new approach to potentiometric sensing utilizing paper-based microfluidic sampling is studied in this work. A solid-contact ion-selective electrode and a solid-contact reference electrode are pressed against a filter paper into which the sample solution is absorbed. The filter paper acts simultaneously as a sampling unit and as a sample container during potentiometric sensing. The paper substrates containing standard and sample solutions are disposable, while the sensors are used multiple times. The analytical method presented here opens new possibilities for economically and ecologically sound measurements of ions in various samples.

Modified ZIF-8 Nanoparticles for Targeted Metabolic Treatment of Acute Spinal Cord Injury.

The activation of proinflammatory M1-type macrophages in the injured lesion accelerates the progression of a spinal cord injury (SCI). However, adverse side effects during systemic treatments targeting M1 macrophages have limited their applications. Nanoplatforms are novel carriers of traditional Chinese medicine because of their great efficiency to deliver and accumulation in the lesion. Herein, we synthesized a modified zeolitic imidazolate framework-8 (ZIF-8) nanoplatform for internalization and accumulation in the injured spinal cord and effective administration for SCI. In vitro and in vivo experiments suggested that Prussian blue and Schisandrin B modified ZIF-8 effectively accumulated in M1 macrophages, inhibited reactive oxygen species (ROS), and polarized the macrophage from proinflammatory M1 to anti-inflammatory M2 for rapid tissue infiltration by reprogramming the metabolic macrophages phenotype. This nanoplatform achieves a synergistic therapeutic effect of immunomodulation and neuroprotection, thereby shedding new light on the application of ZIF-8, and provides great potential for SCI.

Polysaccharides of Plantago asiatica enhance antitumor activity via regulating macrophages to M1-like phenotype.

Monocyte-derived macrophages can be polarized into antitumor M1 phenotype, which inhibited the growth of tumors, and immune-suppressive M2 phenotype, which promoted the development and metastasis of tumors. Plantain polysaccharide (PLP), extracted from the Plantago asiatica, has shown its various biological activities. However, the ability of PLP involved in immune regulation was still obscure. Accordingly, we aimed to investigate whether PLP could polarize macrophages and further inhibit 4T1 tumor cells in vivo and in vitro. In this research, in vitro results showed that PLP displayed the potential in polarizing RAW264.7 macrophages into M1 phenotype and indirect inhibiting migratory effect on 4T1 cells. Furthermore, the phagocytosis and the release of reactive oxygen species (ROS) of macrophages were enhanced. In vivo anti-tumor results demonstrated that PLP could effectively inhibit the growth of 4T1 breast tumors by promoting accumulation of macrophages and T cells in the spleen and lymph node. In conclusion, these findings indicated that PLP inhibited the proliferation and progression of breast tumors by accumulating CD4+, CD8+ T cells and M1-like macrophages in lymph node and spleen, and therefore provided an experimental basis for PLP as a potential antitumor adjunctive therapy in preclinical and clinical trials.

Economic evaluations of 13-valent pneumococcal conjugate vaccine: a systematic review.

INTRODUCTION: Studies on economic evaluations of the 13-valent pneumococcal conjugate vaccine (PCV13) have been increasing over the last decade. No systematic reviews have synthesized the evidence of economic evaluations of the PCV13. AREAS COVERED: We systematically searched the literature which published on peer-reviewed journals from January 2010 to June 2022. The literature search was conducted in the following electronic databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database. We identified 1827 records from the database search. After excluding 511 duplicates, 1314 records were screened, of which 156 records were retained for the full-text reviews. A total of 44 studies were included in the review. Among the included studies, 33 studies were economic evaluations of PCV13 among children, and 11 studies were conducted among adults. The literature search initiated in April, 2022, and updated in June 2022. EXPERT OPINION: Vaccination with PCV13 was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccine or several other pneumococcal vaccines (e.g. PCV10, PPV23). Future research is advised to expand economic evaluations of PCV13 combined with dynamic model to enhance methodologic rigor and prediction accuracy.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics.

BACKGROUND: Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. METHOD: We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. RESULTS: We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. CONCLUSION: In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.

Reference intervals for LC-MS /MS measurements of plasma renin activity, aldosterone, angiotensin II, and 24-hour urinary aldosterone in Northern Chinese Han population.

BACKGROUND: Examination of aldosterone to Renin Ratio (ARR) and plasma aldosterone concentration (PAC) or 24-h urinary aldosterone excretion (24-h UALD) was the necessary tests in confirmatory tests for primary aldosteronism (PA). We developed a combined liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for plasma renin activity (PRA), PAC, and angiotensin II (Ang II) and investigated their reference intervals (RIs) in northern Chinese Han population. The RIs of 24-h UALD excretion were also studied using LC-MS/MS. METHODS: A total of 309 healthy volunteers were recruited in 3 cities in China. PRA, PAC, Ang II, and 24-h UALD were measured using the laboratory-developed LC-MS/MS. Multiple linear regression and the variance component model were applied to determine if the RI needed to be split. The RIs of PRA, PAC, and Ang II were determined using the nonparametric percentile method. RESULTS: The laboratory-developed LC-MS/MS method was verified and showed good performance. Standard deviation ratio (SDR) sex for PAC and SDR region for Ang II are 0.466 and 0.407, respectively, indicating that the RIs of PAC and Ang II must be divided by sex and region, respectively. In addition, the SDR 24hUK for 24-h UALD is 0.579, indicating that the RI of 24-h UALD must be partitioned by urine potassium. CONCLUSION: RIs were established for tests related to the renin-angiotensin-aldosterone system in the apparently healthy northern Chinese Han population by the LC-MS/MS method.

Does Financial Literacy Affect Household Financial Behavior? The Role of Limited Attention.

Financial literacy is essential for every individual concerned with public welfare and household portfolio choices. In this study, we investigate the impact of household financial literacy on individuals' financial behavior using the China Household Financial Survey Data (CHFS) of 2015 and 2017. The results show that financial knowledge has significant current, long-term, and dynamic effects on financial behavior. This finding suggests that financial literacy is an important factor in shaping and improving financial behavior. Second, financial literacy can improve residents' limited attention, and residents with high attention tend to have formal bank accounts, participate in the stock market, and engage in financial behaviors in situations such as risky financial markets. High attention also helps to improve residents' financial behavior. This relationship suggests that financial literacy positively impacts formal bank account holding, participation in financial markets, participation in commercial insurance, participation in pension plans, and credit card holdings through limited attention channels that facilitate access to specific financial information. In addition, heterogeneity analysis showed that the impact of financial literacy on financial behavior differs significantly between urban and rural households, between men and women, and between high and low education levels. The study provides valuable insights for policy implications to enhance financial literacy, such as carrying out financial training to improve residents' knowledge about financial aspects, which further helps to optimize household financial decision-making.

Tumor-associated macrophages in tumor progression and the role of traditional Chinese medicine in regulating TAMs to enhance antitumor effects.

Purpose: To emphasize the importance of tumor-associated macrophages (TAMs) in tumor immunity and to describe the ways in which extracts from Traditional Chinese Medicine (TCM) achieve tumor therapy by modulating macrophages. Significance: By summarizing these available data, this review focused on TAMs and TCM and can build the foundation for future research on antitumor therapeutics. Methods: In this review, we summarized the key functions of TAMs in cancer development and overviewed literature on TCM targeting TAMs together with other immune cells aiming to enhance antitumor immunity. Conclusions: With an indispensable role in antitumor immunity, TAMs contribute to tumor progression, migration, invasion, angiogenesis, lymphangiogenesis, and immunosuppressive microenvironment. In recent years, TCM has gradually gained attention as a potential antitumor adjunctive therapy in preclinical and clinical trials. TCM is also a regulator of cytokine secretion and cell surface molecule expression in balancing the tumor microenvironment (TME), especially macrophage activation and polarization. Therefore, it is believed that TCM could serve as modifiers with immunomodulatory capability.

Analysis of two intestinal bacterial metabolites (trimethylamine N-oxide and phenylacetylglutamine) in human serum samples of patients with T2DM and AMI using a liquid chromatography tandem mass spectrometry method.

BACKGROUND: Trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln) are associated with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). This study developed and validated a simple method firstly for simultaneously quantifying serum TMAO and PAGln using liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: Serum samples from patients with T2DM, AMI, and healthy subjects were analyzed using a new LC-MS/MS method to evaluate TMAO and PAGln levels. Statistical analyses were performed to evaluate TMAO and PAGln distributions among different groups. RESULTS: Retention and separation of the two metabolites were achieved within 5 min. For both analytes, the assay was linear in a 0.02-10 µg/mL range, with >0.99 average linear correlation coefficients, and quantification limit values of approximately 0.010 µg/mL. The average recoveries of TMAO and PAGln were 96.3 % and 96.4 %, respectively. The intra-run and total coefficient variations were 3.5-4.8 % and 3.9-5.7 % respectively for TMAO; and 4.0-5.1 % and 4.6-6.3 % respectively for PAGln. TMAO and PAGln showed a moderate correlation (P < 0.001) and their levels in patients with T2DM were significantly higher than those in healthy individuals (P < 0.001). TMAO levels were higher in patients with T2DM than in patients with AMI (P < 0.01). Patients with AMI had higher PAGln levels than healthy individuals (P < 0.05). After adjusting for sex and age, the top tertile of PAGln was positively correlated with T2DM and AMI while that of TMAO was positively correlated with T2DM. CONCLUSIONS: Overall, a robust isotope dilution LC-MS/MS method was established, which may be beneficial for assessing the association between two metabolites with AMI and T2DM.

Exosomal circRNA_104948 Enhances the Progression of Glioma by Regulating miR-29b-3p and DNMT3B/MTSS1 Signaling.

Glioma is a common type of malignancy in the central nervous system. The pathogenesis of glioma is complex and the underlying mechanisms remain largely unknown. In our study, exosomes were exacted from patient samples, and the isolated exosomes were confirmed by transmission electron microscope. The expression of circRNA_104948, miR-29b-3p and DNMT3B were determined using RT-qPCR. Proliferative activity of cell was examined using CCK-8 assay. Cell apoptotic rate was evaluated by flow cytometry. The expression levels of proliferation or apop-tosis markers were determined using western blotting. Our data suggested that circRNA_104948 was upregulated in plasma exosomes/tissue samples of glioma patients and glioma cell lines. Furthermore, cell proliferation was enhanced and apoptosis was suppressed in normal astrocytes treated with exosomal circRNA_104948, and the effects were reversed by sh-circRNA_104948. In addition, miR-29b-3p is a novel target of circRNA_104948, and DNMT3B is a putative downstream molecule of miR-29b-3p. circRNA_104948 could regulate the proliferation/apoptosis of astrocytes through miR-29b-3p/DNMT3B/MTSS1 signaling, and the biological behavior changes induced by glioma-Exo were reversed by miR-29b-3p mimics; upregulated cell growth caused by miR-29b-3p inhibitors was abrogated by the knockdown of DNMT3B; the effects induced by miR-29b-3p mimics were abolished by the overexpression of DNMT3B. Our findings revealed the important roles of circRNA_104948 on the development of glioma, and circRNA_104948/miR-29b-3p/MTSS1/DNMT3B pathway may be a potential candidate for the target therapy of glioma patients.

Mongolian Medicine Areca Thirteen Pill (GY-13) Improved Depressive Syndrome via upregulating cAMP/PKA/CREB/BDNF signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca Thirteen Pill, also called Gao You-13 (GY-13), is a traditional Mongolian herbal formula and has been extensively used to treat depression in Mongolian areas, which belongs to Heyi disease in Mongolian medicine. Major depressive disorder is a serious psychiatric disease, only one-third of individuals with depression are responsive to current antidepressants in clinic. Growing attention has been attracted by traditional herbal medicines in fighting depression because they are considered safer alternatives to pharmacotherapy. AIM OF THE STUDY: To reveal the mechanism of GY-13 in the treatment of depression. MATERIALS AND METHODS: The rat depression model was established by chronic unpredictable mild stress (CUMS), and primary hippocampal neurons were used to construct a glutamate-induced excitotoxicity model. The antidepressant effect of GY-13 was then assessed by performing sucrose preference tests, open field tests, and body weight measurements on rats. The expression of cAMP and PKA, mRNA levels of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), and hippocampal neuronal apoptosis were measured. RESULTS: The results indicate that GY-13 significantly improves depression-like behavior, rescues decreased cAMP， PKA, recovers the mRNA levels of CREB and BDNF, and increases the proliferative activity of hippocampus. In addition, blockade of PKA reverses the effects of GY-13 treatment on CREB mRNA, BDNF mRNA levels. In vitro, GY-13 treatment increased hippocampal proliferative activity and attenuated Glu-induced apoptosis of hippocampal neurons as well as reduced CREB mRNA and BDNF mRNA expression levels. CONCLUSIONS: Our research demonstrated that GY-13 treatment exerted a potent antidepressant action via activation of cAMP/CREB/BDNF signaling pathway, promoting proliferation, and suppressing apoptosis. This research provides molecular biological ground for developing GY-13 into a potent alternative for the intervention of depression.

A Serum Metabolite Classifier for the Early Detection of Type 2 Diabetes Mellitus-Positive Hepatocellular Cancer.

Type 2 diabetes mellitus (T2DM) has been identified as an independent risk factor for hepatocellular cancer (HCC). However, there are no ideal biomarkers for the surveillance and early detection of HCC in the T2DM population at present. In this study, we aimed to explore novel metabolite biomarkers for T2DM-positive [T2DM(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in T2DM(+) HCC patients in untargeted metabolomic analyses. Targeted metabolite analyses confirmed that serum benzoic acid and citrulline were increased, and creatine was decreased in T2DM(+) HCC compared to the T2DM group. A metabolite classifier including benzoic acid, creatine, and citrulline was identified as a novel biomarker for the diagnosis of T2DM(+) HCC, with an area under the ROC curve (AUC) of 0.93 for discriminating T2DM(+) HCC patients from T2DM patients. In addition, the metabolite classifier detected small-size (AUC = 0.94), early-stage (AUC = 0.94), and AFP-negative (AUC = 0.96) tumors with high sensitivity and specificity. The combination of this metabolite classifier and AFP might be useful in the surveillance and early detection of HCC in the T2DM population. In conclusion, this study establishes a novel diagnostic tool for T2DM(+) HCC.

Circular RNA TTC3 regulates cerebral ischemia-reperfusion injury and neural stem cells by miR-372-3p/TLR4 axis in cerebral infarction.

BACKGROUND: Stroke serves as a prevalent cerebrovascular disorder with severe cerebral ischemia/reperfusion (CIR) injury, in which neural stem cells (NSCs) play critical roles in the recovery of cerebral function. Circular RNAs (circRNAs) have been widely found to participate in stroke and NSC modulation. However, the role of circRNA TTC3 (circTTC3) in the regulation of CIR injury and NSCs remains elusive. Here, we aimed to explore the impact of circTTC3 on CIR injury and NSCs. METHODS: The middle cerebral artery occlusion/repression (MCAO/R) model was established in C57BL/6J mice. The primary astrocytes were isolated from the cerebellum from C57BL/6J mice. The primary NSCs were obtained from rat embryos. The effect of circTTC3 on CIR injury and NSCs was analyzed by TTC staining, qPCR, Western blot, LDH colorimetric kits, MTT assays, Annexin V-FITC Apoptosis Detection Kit, luciferase reporter gene assays, and others in the system. RESULTS: Significantly, the expression of circTTC3 was elevated in the MCAO/R mice and oxygen and glucose deprivation (OGD)-treated astrocytes. The depletion of circTTC3 attenuated cerebral infarction, neurological score, and brain water content. The OGD treatment induced apoptosis and the levels of lactate dehydrogenase (LDH) in the astrocytes, in which circTTC3 depletion reduced this phenotype in the system. Moreover, the depletion of circTTC3 promoted the proliferation and upregulated the nestin and ß-tubulin III expression in NSCs. Mechanically, circTTC3 was able to sponge miR-372-3p, and miR-372-3p can target Toll-like receptor 4 (TLR4) in NSCs. The miR-372-3p inhibitor or TLR4 overexpression could reverse circTTC3 depletion-mediated astrocyte OGD injury and NSC regulation. CONCLUSION: Thus, we conclude that circTTC3 regulates CIR injury and NSCs by the miR-372-3p/TLR4 axis in cerebral infarction. Our finding presents new insight into the mechanism by which circTTC3 modulates CIR injury and NSC dysfunction. CircTTC3, miR-372-3p, and TLR4 may serve as potential targets for the treatment of CIR injury during stroke.

Acupuncture Combined with Chinese Medicine Iontophoresis Treatment for Chronic Progressive Cervical Intervertebral Disk Disease in a Dog.

CASE REPORT: A 12-year-old castrated male dog with nonambulatory tetraplegia was diagnosed with spinal stenosis at C3-C4 through X-ray examination and with ventral extradural spinal compression at C3-C4 through myelography and computed tomography. The diagnosis of traditional Chinese veterinary medicine was local Qi and blood stagnation, spleen Qideficiency, blood deficiency, and kidney Yang deficiency. We initiated treatment using a combination of acupuncture and Chinese medicine iontophoresis with laser therapy. After 12 treatment days, there was a significant improvement in the dog's ambulation function, which was indicated by proper walking and flexible head-turning. CONCLUSION: This indicates that combining acupuncture and Chinese medicine iontophoresis could be a potential treatment for chronic progressive cervical intervertebral disk disease in dogs.

Fermented Deer Blood Ameliorates Intense Exercise-Induced Fatigue via Modulating Small Intestine Microbiota and Metabolites in Mice.

Intense and excessive exercise-induced fatigue has become an important health issue and can damage intestinal health. Deer blood, as a food byproduct with nutritional value, has been found to restore physical strength. However, little is known about the antifatigue effect of fermented deer blood (FDB) on intense exercise mice. The purpose of the present study is to investigate the antifatigue effect of FDB, and whether this effect is correlated with the altered small intestinal microbiota and metabolites in exercise mice. In this study, 5-week-old male C57BL/6J mice are given treadmill exercise with or without FDB supplementation (30 and 150 mg/kg/d) for 3 weeks. FDB significantly reduces metabolic byproduct accumulation, liver and intestinal damage, and enhances glycogen storage and antioxidant capacity in intense exercise mice. Moreover, FDB restructures the small intestinal microbiota by increasing the abundance of probiotics and butyric acid producing bacteria and decreasing the abundance of pathogenic bacteria. FDB also regulates the levels of metabolites involved in TCA cycle and amino acid metabolism in urine and small intestine content. Correlation analysis shows that FDB-modulated microbiota is highly associated with its antifatigue effect. FDB may ameliorate fatigue and intestinal injury through targeting small intestinal microbiota.