Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling.

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

Mediating role of social support in dysphoria, despondency, and quality of life in patients undergoing maintenance hemodialysis.

BACKGROUND: Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis (MHD) that significantly affect their quality of life (QOL). High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD. Currently, there is limited research on how social support mediates the relationship between dysphoria, despondency, and overall QOL in patients undergoing MHD. It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD, ultimately enhancing their overall QOL. AIM: To investigate the mediating role of social support in relationships between dysphoria, despondency, and QOL among patients undergoing MHD. METHODS: Participants comprised 289 patients undergoing MHD, who were selected using a random sampling approach. The Social Support Rating Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and QOL Scale were administered. Correlation analysis was performed to examine the associations between social support, dysphoria, despondency, and QOL in patients undergoing MHD. To assess the mediating impact of social support on dysphoria, despondency, and QOL in patients undergoing MHD, a bootstrap method was applied. RESULTS: Significant correlations among social support, dysphoria, despondency, and quality in patients undergoing MHD were observed (all P < 0.01). Dysphoria and despondency negatively correlated with social support and QOL (P < 0.01). Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD (P < 0.05). The direct effect of dysphoria on QOL was statistically significant (P < 0.05). Social support mediated the relationship between dysphoria and QOL, and this mediating effect was significant (P < 0.05). Similarly, the direct effect of despondency on QOL was significant (P < 0.05). Moreover, social support played a mediating role between despondency and QOL, with a significant mediating effect (P < 0.05). CONCLUSION: These findings suggest that social support plays a significant mediating role in the relationship between dysphoria, despondency, and QOL in patients undergoing MHD.

[Critical Review on Heavy Metal Contamination in Urban Soil and Surface Dust].

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.

Efficacy comparison between acupuncture and other modalities in the treatment of rotator cuff diseases: meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to analyze the efficacy of acupuncture alone or combined with physical therapy compared to other treatment interventions for relieving pain and improving function in rotator cuff diseases. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After PROSPERO (CRD42023396740) registration, all randomized controlled trials (RCTs) published from the inception of the databases to October 10, 2023, evaluating the efficacy of acupuncture either alone or in combination with physical therapy for treating rotator cuff diseases, were extracted from seven databases, including PubMed, Embase, the Web of Science, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), the VIP Database for Chinese Technical Periodicals (VIP), and the Wanfang Date. Two independent researchers assessed the quality of the included studies and extracted relevant data. Furthermore, a meta-analysis was conducted using Stata 14 software. RESULTS: We included 13 RCTs - 12 published in English and 1 in Chinese - that enrolled 1,371 patients. The meta-analysis results demonstrated that acupuncture alone or in combination with physical therapy was superior to other interventions for short-term shoulder joint function improvement (standardized mean difference [SMD] = -0.82, 95% confidence interval [95% CI]: -1.28 to -0.35, P = 0.001), medium-term shoulder joint function improvement (SMD = -1.00, 95% CI: -1.62 to -0.38, P = 0.002), short-term pain relief (weighted mean difference [WMD] = -1.37, 95% CI: -2.39 to -0.38, P = 0.006), medium-term pain relief (WMD = -1.66, 95% CI: -2.70 to -0.63, P = 0.002), and post-treatment shoulder joint abduction improvements (SMD = 0.68, 95% CI: 0.20 to 1.16, P = 0.005), external rotation (SMD = 0.62, 95% CI: 0.13 to 1.11, P = 0.012), and forward flexion (SMD = 0.71, 95% CI: 0.44 to 0.97, P < 0.001), with significant differences (P < 0.05). CONCLUSION: Based on the current clinical data, meta-analysis showed that acupuncture alone or combined with physical therapy is efficacious for short- and medium-term (< 3 months) pain relief and functional improvements. However, compared to other interventions, the efficacy of the long-term (3 to 12 months) period did not significantly differ. After treatment, these modalities displayed advantages such as improved shoulder joint abduction, external rotation, and forward flexion movements. However, no significant difference was noted in internal rotation movement. Thus, future studies might further investigate whether different acupuncture methods affect the efficacy of treating rotator cuff diseases and improving long-term outcome.

Long-term low-dose lamotrigine for paroxysmal kinesigenic dyskinesia: a two-year investigation of cognitive function in children.

Objective: While low-dose lamotrigine has shown effectiveness in managing paroxysmal kinesigenic dyskinesia (PKD) in pediatric populations, the cognitive consequences of extended use are yet to be fully elucidated. This study seeks to assess the evolution of cognitive functions and the amelioration of attention deficit and hyperactivity disorder (ADHD) symptoms following a two-year lamotrigine treatment in children. Methods: This investigation employed an open-label, uncontrolled trial design. Between January 2008 and December 2021, thirty-one participants, ranging in age from 6.5 to 14.1 years, were enrolled upon receiving a new diagnosis of PKD, as defined by the clinical diagnostic criteria set by Bruno in 2004. Comprehensive evaluation of PRRT2 variants and 16p11.2 microdeletion was achieved using whole-exome sequencing (WES) and bioinformatics analysis of copy number variant (CNV) for all subjects. Immediately after diagnosis, participants commenced treatment with low-dose lamotrigine. Cognitive function was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR) at baseline and after 2 years, with ADHD diagnoses and symptom severity simultaneously assessed by experts in accordance with the DSM-IV diagnostic criteria for ADHD and the ADHD Rating Scale-IV (ADHD-RS-IV). Results: Initially, twelve out of 31 patients (38.7%) presented with comorbid ADHD. The latency to treatment initiation was notably longer in PKD patients with ADHD (30.75 ± 12.88 months) than in those without ADHD (11.66 ± 9.08 months), t = 4.856, p<0.001. Notably, patients with a latency exceeding 2 years exhibited a heightened risk for comorbid ADHD (OR = 4.671, P=0.015) in comparison to those with shorter latency. Out of the cohort, twenty-five patients saw the clinical trial to its completion. These individuals demonstrated a marked elevation in WISC-CR scores at the 2-year mark relative to the outset across FSIQ (baseline mean: 108.72 ± 10.45 vs 24 months: 110.56 ± 10.03, p=0.001), VIQ (baseline mean: 109.44 ± 11.15 vs 24 months: 110.80 ± 10.44, p=0.028), and PIQ domains (baseline mean: 106.52 ± 9.74 vs 24 months: 108.24 ± 9.38, p=0.012). Concurrently, a substantial mitigation was observed in ADHD inattention at 2 years compared to baseline (p<0.001), with an average total subscale scores decrement from 9.04 ± 4.99 to 6.24 ± 4.05. Conclusion: Prolonged duration of untreated PKD in children may elevate the risk of ADHD comorbidity. Notably, following a 2-year lamotrigine regimen, enhancements were observed in both cognitive test outcomes and ADHD symptomatology.

Less common phenotypes of myelin oligodendrocyte glycoprotein antibody-related diseases in children deserve more attention.

BACKGROUND: To facilitate the identification of less common clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children. METHODS: We retrospectively reviewed medical records of 236 patients with MOGAD. The following phenotypes were considered to be typical for MOGAD: ADEM, ON, TM, and NMOSD. Less common onset clinical phenotypes were screened out; their clinical and magnetic resonance imaging (MRI), diagnosis, treatment, and prognosis were summarized and analyzed. RESULTS: 16 cases (6.8%) presented as cortical encephalitis, with convulsions, headache, and fever as the main symptoms. 15 cases were misdiagnosed in the early period. 13 cases (5.5%) showed the overlapping syndrome of MOGAD and anti-N-methyl-D aspartate receptor encephalitis (MNOS), with seizures (92.3%) being the most common clinical symptom. 11 cases (84.6%) showed relapses. The cerebral leukodystrophy-like phenotype was present in seven cases (3.0%), with a recurrence rate of 50%. Isolated seizures without any findings on MRI phenotype was present in three cases (1.3%), with the only clinical symptom being seizures of focal origin. Three cases (1.3%) of aseptic meningitis phenotype presented with prolonged fever. CONCLUSION: 40/236 (16.9%) of children with MOGAD had less common phenotypes. Less common clinical phenotypes of pediatric MOGAD are susceptible to misdiagnosis and deserve more attention. IMPACT: This is the first comprehensive analysis and summary of all less commonl clinical phenotypes of MOGAD in children, while previous studies have only focused on a specific phenotype or case reports. We analyzed the characteristics of MOGAD in children and further revealed the reasons why these less common clinical phenotypes are prone to misdiagnosis and deserve more attention. Our research on treatment has shown that early detection of MOG antibodies and early treatment are of great significance for improving the prognosis of these patients.

Complete genome sequence of Psychrobacter cibarius AOSW16051, a trimeric autotransporter adhesin synthesizing bacterium isolated from the Baltic Sea.

Bacteria of the genus Psychrobacter are widely distributed in the global low-temperature marine environment and have been studied for their effects on the settlement and metamorphosis of marine invertebrates. Psychrobacter cibarius AOSW16051 was isolated from the surface water samples of the Baltic Sea on the edge of the Arctic Ocean. Here, we present the complete genome of strain AOSW16051, which consists of a circular chromosome composed of 3,425,040 nucleotides with 42.98% G + C content and a circular plasmid composed of 5846 nucleotides with 38.66% G + C content. The genes predicted in this strain showed its strong outer membrane system, type VI secretion system and adhesion system. Trimeric autotransporter adhesins (TAAs) has been identified in the genome of P. cibarius AOSW16051, which has a variety of biological functions in interacting with host cells. However, there are no reports on TAAs in marine bacteria and aquatic pathogenic bacteria. By analyzing the genomic data, we can gain valuable insights to enhance our understanding of the physiological characteristics of P. cibarius, as well as the biological functions of TAAs and their role in triggering metamorphosis of invertebrate larvae.

Methyl jasmonate regulation of pectin polysaccharides in Cosmos bipinnatus roots: A mechanistic insight into alleviating cadmium toxicity.

Methyl jasmonate (MeJA), a crucial phytohormone, which plays an important role in resistance to Cadmium (Cd) stress. The cell wall (CW) of root system is the main location of Cd and plays a key role in resistance to Cd toxicity. However, the mechanism effect of MeJA on the CW composition and Cd accumulation remain unclear. In this study, the contribution of MeJA in regulating CW structure, pectin composition and Cd accumulation was investigated in Cosmos bipinnatus. Phenotypic results affirm MeJA's significant role in reducing Cd-induced toxicity in C. bipinnatus. Notably, MeJA exerts a dual impact, reducing Cd uptake in roots while increasing Cd accumulation in the CW, particularly bound to pectin. The molecular structure of pectin, mainly uronic acid (UA), correlates positively with Cd content, consistent in HC1 and cellulose, emphasizing UA as pivotal for Cd binding. Furthermore, MeJA modulates pectin methylesterase (PME) activity under Cd stress, influencing pectin's molecular structure and homogalacturonan (HG) content affecting Cd-binding capacity. Chelate-soluble pectin (CSP) within soluble pectins accumulates a substantial Cd proportion, with MeJA regulating both UA content and the minor component 3-deoxy-oct-2-ulosonic acid (Kdo) in CSP. The study delves into the intricate regulation of pectin monosaccharide composition under Cd stress, revealing insights into the CW's physical defense and Cd binding. In summary, this research provides novel insights into MeJA-specific mechanisms alleviating Cd toxicity in C. bipinnatus, shedding light on complex interactions between MeJA, and Cd accumulation in CW pectin polysaccharide.

Human amniotic MSCs-mediated anti-inflammation of CD206hiIL-10hi macrophages alleviates isoproterenol-induced ventricular remodeling in mice.

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) derived from amniotic membrane have multilineage differentiation, immunosuppressive, and anti-inflammation which makes them suitable for the treatment of various diseases. OBJECTIVE: This study aimed to explore the therapeutic effect and molecular mechanism of hAMSCs in ventricular remodeling (VR). METHODS: hAMSCs were characterized by a series of experiments such as flow cytometric analysis, immunofluorescence, differentiative induction and tumorigenicity. Mouse VR model was induced by isoproterenol (ISO) peritoneally, and the therapeutic effects and the potential mechanisms of hAMSCs transplantation were evaluated by echocardiography, carboxy fluorescein diacetate succinimidyl ester (CFSE) labeled cell tracing, histochemistry, qRT-PCR and western blot analysis. The co-culturing experiments were carried out for further exploring the mechanisms of hAMSCs-derived conditioned medium (CM) on macrophage polarization and fibroblast fibrosis in vitro. RESULTS: hAMSCs transplantation significantly alleviated ISO-induced VR including cardiac hypertrophy and fibrosis with the improvements of cardiac functions. CFSE labeled hAMSCs kept an undifferentiated state in heart, indicating that hAMSCs-mediated the improvement of ISO-induced VR might be related to their paracrine effects. hAMSCs markedly inhibited ISO-induced inflammation and fibrosis, seen as the increase of M2 macrophage infiltration and the expressions of CD206 and IL-10, and the decreases of CD86, iNOS, COL3 and αSMA expressions in heart, suggesting that hAMSCs transplantation promoted the polarization of M2 macrophages and inhibited the polarization of M1 macrophages. Mechanically, hAMSCs-derived CM significantly increased the expressions of CD206, IL-10, Arg-1 and reduced the expressions of iNOS and IL-6 in RAW264.7 macrophages in vitro. Interestingly, RAW264.7-CM remarkably promoted the expressions of anti-inflammatory factors such as IL-10, IDO, and COX2 in hAMSCs. Furthermore, the CM derived from hAMSCs pretreated with RAW264.7-CM markedly inhibited the expressions of fibrogenesis genes such as αSMA and COL3 in 3T3 cells. CONCLUSION: Our results demonstrated that hAMSCs effectively alleviated ISO-induced cardiac hypertrophy and fibrosis, and improved the cardiac functions in mice, and the underlying mechanisms might be related to inhibiting the inflammation and fibrosis during the ventricular remodeling through promoting the polarization of CD206hiIL-10hi macrophages in heart tissues. Our study strongly suggested that by taking the advantages of the potent immunosuppressive and anti-inflammatory effects, hAMSCs may provide an alternative therapeutic approach for prevention and treatment of VR clinically.

Inhibitory effect of acupoint electrostimulation with different layers and intensities on muscular inflammatory pain and spinal WDR neuron activity. / ç©´ä½ä¸åŒå±‚æ¬¡å’Œå¼ºåº¦ç”µåˆºæ¿€ç¼“è§£è‚Œè‚‰ç‚Žæ€§ç—›åŠå¯¹è„Šé«“èƒŒè§’å¹¿åŠ¨åŠ›ç¥žç»å ƒçš„æŠ‘åˆ¶ä½œç”¨.

OBJECTIVES: To observe the analgesic effects of different levels and intensities of electrical stimulation on the local acupoints in the pain source area and their impact on wide dynamic range (WDR) neurons in the spinal dorsal horn, in order to provide a basis for selecting appropriate parameters for electroacupuncture (EA) stimulation. METHODS: Wistar rats were used in 3 parts of the experiment. Complete Freund's adjuvant was used to establish a model of inflammation-induced pain in the gastrocnemius muscle. After modeling, 6 rats were randomly selected for multi-channel extracellular electrophysiological recording of the electrical activity of WDR neurons, to determine the threshold for activating the A-component (Ta) and the C-component (Tc), which were used as the intervention intensities for skin transcutaneous electrical acupoint stimulation (TEAS) or EA. Thirty-six rats were randomly divided into normal , model , TEAS-Ta , TEAS-Tc, EA-Ta , and EA-Tc groups, with 6 rats in each group. In the pain source area , Ta or Tc intensity of TEAS or EA intervention at"Chengshan"(BL57) was performed for 30 min each time, once a day, for 3 consecutive days. A small animal pressure pain measurement instrument was used to measure the mechanical pressure pain threshold of the gastrocnemius muscle in rats, and the Von Frey filament was used to measure the mechanical pain threshold of the footpad. Thirteen rats were randomly selected to observe the immediate responsiveness of WDR neurons to Ta/Tc intensity of EA or TEAS in BL57. RESULTS: The thresholds of TEAS to activate WDR neuron A-component or C-component were (2.43±0.57) mA and (7.00±1.34) mA, respectively, while the thresholds for EA to activate muscle WDR neuron A-component or C-component were (0.72±0.34) mA and (1.58±0.35) mA, respectively. After injection of CFA into the gastrocnemius muscle, compared with the normal group both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad of rats in the model group were significantly decreased (P<0.001). After TEAS-Ta, TEAS-Tc or EA-Ta intervention in the BL57, both the mechanical pressure pain threshold of the gastrocnemius muscle and the mechanical pain threshold of the footpad were significantly higher than those in the model group (P<0.05, P<0.001). Compared with the normal group, the electrical threshold for evoking WDR neuron C-component discharge was significantly decreased (P<0.001) in the model group, while increased after TEAS-Ta, TEAS-Tc, or EA-Ta intervention (P<0.01) compared with the model group. The evoked discharge frequency of muscle WDR neurons decreased significantly after immediate intervention with TEAS-Ta, TEAS-Tc, or EA-Ta (P<0.01, P<0.05). EA-Tc had no significant improvement on the evoked electrical activity of WDR neurons or pain behavior. CONCLUSIONS: TEAS-Ta, TEAS-Tc, or EA-Ta can all alleviate the local and footpad mechanical pain in rats with muscle inflammation and inhibit the responsiveness of WDR neurons, indicating that different intensities are required for analgesic effects at different levels of acupoints in the pain source area.

STAT4-Mediated Klotho Up-Regulation Contributes to the Brain Ischemic Tolerance by Cerebral Ischemic Preconditioning via Inhibiting Neuronal Pyroptosis.

Our previous study has proved that the Klotho up-regulation participated in cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance. However, the exact neuroprotective mechanism of Klotho in CIP remains unclear. We explored the hypothesis that STAT4-mediated Klotho up-regulation contributes to the CIP-induced brain ischemic tolerance via inhibiting neuronal pyroptosis. Firstly, the expressions of pyroptosis-associated proteins (i.e., NLRP3, GSDMD, pro-caspase-1, and cleaved caspase-1) in hippocampal CA1 region were determined during the process of brain ischemic tolerance. We found the expression of pyroptosis-associated proteins was significantly up-regulated in the ischemic insult (II) group, and showed no significant changes in the CIP group. The expression level of each pyroptosis-associated proteins was lower in the CIP + II group than that in the II group. Inhibition of Klotho expression increased the expression of pyroptosis-associated proteins in the CIP + II group and blocked the CIP-induced brain ischemic tolerance. Injection of Klotho protein decreased the expression of pyroptosis-associated proteins in the II group, and protected neurons from ischemic injury. Secondly, the transcription factor STAT4 of Klotho was identified by bioinformatic analysis. Double luciferase reporter gene assay and chromatin immunoprecipitation assay showed STAT4 can bind to the site between nt - 881 and - 868 on the Klotho promoter region and positively regulates Klotho expression. Moreover, we found CIP significantly enhanced the expression of STAT4. Knockdown STAT4 suppressed Klotho up-regulation after CIP and blocked the CIP-induced brain ischemic tolerance. Collectively, it can be concluded that STAT4-mediated the up-regulation of Klotho contributed to the brain ischemic tolerance induced by CIP via inhibiting pyroptosis.

Construction of Bridged Benzazepines via Photo-Induced Dearomatization.

Bridged benzazepine scaffolds, possessing unique structural and physicochemical activities, are widespread in various natural products and drugs. The construction of these skeletons often requires elaborate synthetic effort with low efficiency. Herein, we develop a simple and divergent approach for constructing various bridged benzazepines by a photocatalytic intermolecular dearomatization of naphthalene derivatives with readily available α-amino acids. The bridged motif is created via a cascade sequence involving photocatalytic 1,4-hydroaminoalkylation, alkene isomerization and cyclization. Interestingly, the diastereoselectivity can be regulated through different reaction modes in the cyclization step. Moreover, aminohydroxylation and its further bromination have also been demonstrated to access highly functionalized bridged benzazepines. Preliminary mechanistic studies have been performed to get insights into the mechanism. This method provides a divergent synthetic approach for construction of highly functionalized bridged benzazepines, which have been otherwise difficult to access.

The Role of Astrocytic Mitochondria in the Pathogenesis of Brain Ischemia.

The morbidity rate of ischemic stroke is increasing annually with the growing aging population in China. Astrocytes are ubiquitous glial cells in the brain and play a crucial role in supporting neuronal function and metabolism. Increasing evidence shows that the impairment or loss of astrocytes contributes to neuronal dysfunction during cerebral ischemic injury. The mitochondrion is increasingly recognized as a key player in regulating astrocyte function. Changes in astrocytic mitochondrial function appear to be closely linked to the homeostasis imbalance defects in glutamate metabolism, Ca2+ regulation, fatty acid metabolism, reactive oxygen species, inflammation, and copper regulation. Here, we discuss the role of astrocytic mitochondria in the pathogenesis of brain ischemic injury and their potential as a therapeutic target.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population: a new approach.

AIM: To study retinal microvascular and microstructural alterations in meibomian gland dysfunction (MGD) in severely obese population using optical coherence tomography angiography (OCTA). METHODS: Twelve MGD patients with severely obese population (PAT group; 24 eyes) and 12 healthy controls (HC group; 24 eyes) were recruited. OCTA images were segmented into five [superior (S), nasal (N), inferior (I), temporal (T), and central foveal (C)] or nine [inner superior (IS), outer superior (OS), inner nasal (IN), outer nasal (ON), inner inferior (II), outer inferior (OI), inner temporal (IT), outer temporal (OT), and C] subregions. The superficial vessel density (SVD), retinal thickness (RT), foveal avascular zone (FAZ) parameters, and retinal volume were measured. RESULTS: Visual acuity was significantly different between two groups (0.8±0.17 in PAT group vs 0.2±0.06 in HC group). SVD was significantly lower in PATs in N, T, OS, IN, OT, and ON. The area under the receiver operating characteristic curve (AUC) for T was 0.961 [95% confidence interval (CI): 0.908 to 1.000], for OS was 0.962 (95%CI: 0.915 to 1.000). RT was significantly lower in PATs in IS, OS, OI, OT, ON, IT, IN, and II. AUC for OT was 0.935 (95%CI: 0.870 to 0.999), for IS was 0.915 (95% CI: 0.838 to 0.992). Angiography results showed significantly lower area and perimeter of FAZ, SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group. CONCLUSION: Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures. These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Nucleophilic aromatization of monoterpenes from isoprene under nickel/iodine cascade catalysis.

As a large number of organic compounds possessing two isoprene units, monoterpenes and monoterpenoids play important roles in pharmaceutical, cosmetic, agricultural, and food industries. In nature, monoterpenes are constructed from geranyl pyrophosphate (C10) via various transformations. Herein, the bulk C5 chemical-isoprene, is used for the creation of various monoterpenoids via a nucleophilic aromatization of monoterpenes under cascade catalysis of nickel and iodine. Drugs and oil mixtures from conifer and lemon can be convergently transformed to the desired monoterpenoid. Preliminary mechanistic studies are conducted to get insights about reaction pathway. Two types of cyclic monoterpenes can be respectively introduced onto two similar heterocycles via orthogonal C-H functionalization. And various hybrid terpenyl indoles are programmatically assembled from abundant C5 or C10 blocks. This work not only contributes a high chemo-, regio-, and redox-selective transformation of isoprene, but also provides a complementary approach for the creation of unnatural monoterpenoids.

Effectiveness of acupuncture treatment for stroke and stroke complications: a protocol for meta-analysis and systematic review based on randomized, single-blind, controlled trials.

Introduction: The treatment and rehabilitation of stroke and its complications have become major global health issues. Acupuncture is widely used as a complementary and alternative treatment for stroke. Many clinical studies have evaluated the efficacy and safety of acupuncture, but the research results need to be more consistent. The quality of research based on previously published meta-analyzes is uneven, leading to unstable conclusions. This study aims to provide a comprehensive and systematic analysis of the efficacy of high-quality, randomized controlled trials (RCTs) based on blinded designs for treating stroke and its complications. It also aims to review the characteristics of blinded designs and the current use of sham/placebo acupuncture controls in treating stroke. Methods and analysis: This study will be conducted under the reporting guidelines for systematic reviews and meta-analyzes. Randomized controlled trials using acupuncture as the primary measure for stroke will be searched in databases such as China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wan-fang, PubMed, Embase, Cochrane Library, and Web of Science. To evaluate high-quality research based on a blind design, if the trial evaluates the efficacy of any acupuncture intervention by including a sham/placebo acupuncture control, it will be included. The primary outcome indicator will be the ability to perform daily activities. Secondary outcome indicators include evaluating quality of life and related functions in stroke-related sequelae. We will assess the quality of evidence, reporting quality, and risk of bias for the acupuncture intervention in the literature included in this study using the GRADE system, the STRICTA 2010 checklist, and ROB2.0, respectively. RevMan 5.4 software will be used to conduct the meta-analysis, and Stata 15.0 software will be used for sensitivity analysis and publication bias testing. Discussion: By analyzing high-quality, well-designed, randomized controlled trials of acupuncture, the results of this study may contribute to a more objective and standardized evaluation of acupuncture efficacy in treating stroke and its complications.Systematic review registration: PROSPERO, Identifier (CRD42023378930).

A Functional Magnetic Resonance Imaging Study Using Dynamic Amplitude of Low-Frequency Fluctuation to Assess Brain Activity in Patients with Moyamoya Disease.

Introduction: The purpose of this study was to monitor and record the dynamic brain activity of patients with moyamoya disease (MMD), as well as to study the relationship between brain abnormalities and presenting clinical features. Methods: A total of 16 patients with MMD (2 males and 14 females) were invited to participate in the study, as were healthy controls (HCs) with the same number and sex ratio. In this study, the dynamic amplitude of low-frequency fluctuation (dALFF) was utilized to assess changes in spontaneous brain activity. Moreover, we also used correlation analysis to study the relationship among the measured mean of dALFF, behavioral performances, and the retinal nerve fiber layer and the Hospital Anxiety and Depression Scale (HADS) score to explore the potential relationship between MMD and anxiety and depression. Results: Our study reveals that in MMD, dALFF levels decreased in the left lingual gyrus, right insula, and occipital lobe. Discussion: In this study, we found and discussed the potential relationship between the abnormal activities in multiple brain regions and related functional network disorders in patients with MMD, as well as the damage to brain regions that process emotion and vision, in the hopes of providing more ideas for the clinical diagnosis and treatment of MMD.

Development and validation of a fully automatic tissue delineation model for brain metastasis using a deep neural network.

Background: Stereotactic radiosurgery (SRS) treatment planning requires accurate delineation of brain metastases, a task that can be tedious and time-consuming. Although studies have explored the use of convolutional neural networks (CNNs) in magnetic resonance imaging (MRI) for automatic brain metastases delineation, none of these studies have performed clinical evaluation, raising concerns about clinical applicability. This study aimed to develop an artificial intelligence (AI) tool for the automatic delineation of single brain metastasis that could be integrated into clinical practice. Methods: Data from 426 patients with postcontrast T1-weighted MRIs who underwent SRS between March 2007 and August 2019 were retrospectively collected and divided into training, validation, and testing cohorts of 299, 42, and 85 patients, respectively. Two Gamma Knife (GK) surgeons contoured the brain metastases as the ground truth. A novel 2.5D CNN network was developed for single brain metastasis delineation. The mean Dice similarity coefficient (DSC) and average surface distance (ASD) were used to assess the performance of this method. Results: The mean DSC and ASD values were 88.34%±5.00% and 0.35±0.21 mm, respectively, for the contours generated with the AI tool based on the testing set. The DSC measure of the AI tool's performance was dependent on metastatic shape, reinforcement shape, and the existence of peritumoral edema (all P values <0.05). The clinical experts' subjective assessments showed that 415 out of 572 slices (72.6%) in the testing cohort were acceptable for clinical usage without revision. The average time spent editing an AI-generated contour compared with time spent with manual contouring was 74 vs. 196 seconds, respectively (P<0.01). Conclusions: The contours delineated with the AI tool for single brain metastasis were in close agreement with the ground truth. The developed AI tool can effectively reduce contouring time and aid in GK treatment planning of single brain metastasis in clinical practice.

Determinants of acute and subacute case-fatality in elderly patients with hypertensive intracerebral hemorrhage.

Background: Given that limited reports have described the survival and risk factors for elderly patients with hypertensive intracerebral hemorrhage (HICH), we aimed to develop a valid but simple prediction nomogram for the survival of HICH patients. Methods: All elderly patients ≥65 years old who were diagnosed with HICH between January 2011 and December 2019 were identified. We performed the least absolute shrinkage and selection operator (Lasso) on the Cox regression model with the R package glmnet. A concordance index was performed to calculate the nomogram discrimination; and calibration curves and decision curves were graphically evaluated by depicting the observed rates against the probabilities predicted by the nomogram. Results: A total of 204 eligible patients were analyzed, and over 20 % of the population was above the age of 80 (65-79 years old, n = 161; 80+ years old, n = 43). A hematoma volume ≥13.64 cm3 was associated with higher 7-day mortality (OR = 6.773, 95 % CI = 2.622-19.481; p < 0.001) and higher 90-day mortality (OR = 3.955, 95 % CI = 1.611-10.090, p = 0.003). A GCS score between 13 and 15 at admission was associated with a 7-day favorable outcome (OR = 0.025, 95 % CI = 0.005-0.086; p < 0.001) and a 90-day favorable outcome (OR = 0.033, 95 % CI = 0.010-0.099; p < 0.001). Conclusions: Our nomogram models were visualized and accurate. Neurosurgeons could use them to assess the prognostic factors and provide advice to patients and their relatives.