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IntroductionIschemic stroke is a leading cause of morbidity and mortality in older adults. Therefore, in this study, we sought to understand the interplay between the microbiota, gut, and brain in the context of stroke in older adults.ObjectiveTo determine whether gut microbiota from younger individuals promotes recovery through angiogenesis in both elderly stroke patients and aged stroke mice, we explored the changes in gut microbiota and the correlation between short-chain fatty acids (SCFAs) and angiogenesis in the aged stroke population. Then, we altered the gut microbiome in aged mice by transplanting microbiota from younger donors before inducing experimental stroke to explore the mechanism by which gut microbiota-derived SCFAs promote angiogenesis.MethodsPart I: We conducted a single-center, double-blind trial to compare gut microbiota diversity and SCFA levels in fecal samples from older stroke patients with those from younger stroke patients. Additionally, we measured levels of vascular endothelial growth factor (VEGF) and VEGFC levels in plasma to assess their correlation with SCFA levels. Part II: We performed fecal microbiota transplantation (FMT) 3 days before inducing ischemic stroke in aged male mice (16–18) via distal middle cerebral artery occlusion (dMCAO). The FMT was conducted using gut microbiomes from either young donors (2–3 months) or aged donors (16–18 months).ResultsIn older stroke patients, gut microbiota diversity was significantly reduced compared to that in younger stroke patients. Furthermore, levels of acetate, a bacterially derived SCFA, were lower and positively correlated with angiogenesis markers (VEGF and VEGF-C). In aged stroke mice, transplantation of young microbiota improved stroke outcomes by promoting angiogenesis, which was facilitated by lymphatic ingrowth into the cortex. This protective effect was linked to gut microbiota-derived acetate, which enhanced lymphangiogenesis by replenishing acetyl coenzyme A.Conclusions(a) Gut microbiota-derived acetate promotes angiogenesis post-stroke and (b) lymphatic ingrowth into the cerebral cortex was observed in post-dMCAO mice. These findings suggest that selectively promoting SCFA-producing bacteria, particularly acetate-producers, could be a promising therapeutic strategy to reduce functional impairments in older stroke subjects.

ObjectivesTo explore the association of Children's Dietary Inflammatory Index (C-DII) scores with inflammation and markers of inflammatory factors in children and adolescents.MethodsData on dietary nutrient intake, markers of inflammation (ferritin, alkaline phosphatase, C-reactive protein (CRP), absolute neutrophil cell count and lymphocyte count) and oxidative stress (serum bilirubin, albumin, and iron) were available for participants aged 6–19 years (n = 1281). Each participant's C-DII score was calculated based on a 24-h diet and recall. Generalized linear models were applied to examine associations between C-DII and markers of inflammation and oxidative stress, while adjusting for covariates. Restricted cubic splines were used to explore the dose-response association of C-DII scores with indicators of inflammatory oxidative stress. Akaike's Information Criterionwas applied to compare the performance of linear and non-linear models.ResultsAfter adjusting for potential confounders, quantile regression results showed that when comparing C-DII quartile 4 (most pro-inflammatory) and quartile 1 (most anti-inflammatory), lymphocytes, ferritin, CRP were statistically significant differences in serum bilirubin, albumin and serum iron (P < 0.05). The C-DII score showed a non-linear relationship with inflammatory oxidative stress indicators. Overweight/obese children and adolescents who ate a high pro-inflammatory diet were more likely to have higher levels of inflammatory cytokines (P = 0.002).ConclusionsThe dietary inflammatory index in children is associated with markers of chronic inflammation and oxidative stress. A pro-inflammatory diet resulted in increased serum concentrations of these markers, implying that early dietary interventions have implications for reducing chronic inflammation and oxidative stress in children and adolescents.

Addressing global climate change is the responsibility of all mankind, and original green technology innovation is the key to achieving the goal of “carbon neutrality”. Under the target of “carbon neutrality”, it remains to be seen whether China’s special economic zones can promote the green technology innovation of enterprises, which is very important for achieving green and high-quality development. This study examines the impact of special economic zones (SEZs) on enterprises’ green technology innovation by constructing a quasi-natural experiment using data of Chinese listed companies (collected from 2000 to 2017) and green patent applications. The empirical results showed that the SEZ program significantly promoted the green technology innovation of enterprises. The number of green patent applications of enterprises in zones has increased by 17.02%. The promotion effect was more significant on enterprises in provincial development zones, those that are owned by the central state, and those in central and eastern regions. In the short term, the green innovation promotion effect is mainly derived from the effect of preferential policy subsidies, while in the long run, the role of the agglomeration effect gradually emerged. This study provides empirical evidence for green and high-quality development. This study also provides a new policy reference for achieving a win–win situation between industrial agglomeration and ecological environment.

Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P < 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P < 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P < 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P < 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. The paucity of good animal models hinders our understanding of the pathophysiology of PA and the hypertensive mechanism of PA remains incompletely known. It was recently reported that genetic deletion of TWIK-related acid-sensitive potassium-1 and potassium-3 channels from mice (TASK−/−) generates aldosterone excess and mild hypertension. We addressed the hypertensive mechanism by assessing autonomic regulation of cardiovascular activity in this TASK−/− mouse line that exhibits the hallmarks of PA. Here, we demonstrate that TASK−/− mice were hypertensive with 24-h ambulatory arterial pressure. Either systemic or central blockade of the mineralocorticoid receptor (MR) markedly reduced elevated arterial pressure to normal level in TASK−/− mice. The response of heart rate to the muscarinic cholinergic receptor blocker atropine was similar between TASK−/− and wild-type mice. However, the responses of heart rate to the β-adrenergic receptor blocker propranolol and of arterial pressure to the ganglion blocker hexamethonium were enhanced in TASK−/− mice relative to the counterparts. Moreover, the bradycardiac rather than tachycardiac gain of the arterial baroreflex was significantly attenuated and blockade of MRs to a large degree rescued the dysautonomia and baroreflex gain in TASK−/− mice. Overall, the present study suggests that the MR-dependent dysautonomia and reduced baroreflex gain contribute to the development of hyperaldosteronism-related hypertension.

Leptin is an adipose-derived hormone that plays an important role in the regulation of breathing. It has been demonstrated that obesity-related hypoventilation or apnea is closely associated with leptin signaling pathways. Perturbations of leptin signaling probably contribute to the reduced sensitivity of respiratory chemoreceptors to hypoxia/hypercapnia. However, the underlying mechanism remains incompletely understood. The present study is to test the hypothesis that leptin signaling contributes to modulating a hypoxic ventilatory response. The respiratory function was assessed in conscious obese Zucker rats or lean littermates treated with an injection of leptin. During exposure to hypoxia, the change in minute ventilation was lower in obese Zucker rats than chow-fed lean littermates or high fat diet-fed littermates. Such a change was abolished in all groups after carotid body denervation. In addition, the expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT3), as well as putative O2-sensitive K+ channels including TASK-1, TASK-3 and TASK-2 in the carotid body, was significantly reduced in obese Zucker rats compared with the other two phenotype littermates. Chronic administration of leptin in chow-fed lean Zucker rats failed to alter basal ventilation but vigorously increased tidal volume, respiratory frequency, and therefore minute volume during exposure to hypoxia. Likewise, carotid body denervation abolished such an effect. In addition, systemic leptin elicited enhanced expression of pSTAT3 and TASK channels. In conclusion, these data demonstrate that leptin signaling facilitates hypoxic ventilatory responses probably through upregulation of pSTAT3 and TASK channels in the carotid body. These findings may help to better understand the pathogenic mechanism of obesity-related hypoventilation or apnea.