Dl-3-n-Butylphthalide Alleviates Secondary Brain Damage and Improves Working Memory After Stroke in Cynomolgus Monkeys.

BACKGROUND: Remote secondary neurodegeneration is associated with poststroke cognitive impairment (PSCI). Dl-3-n-butylphthalide (NBP) improves PSCI clinically. However, whether it ameliorates PSCI by alleviating secondary neurodegeneration remains uncertain. Nonhuman primates provide more relevant models than rodents for human stroke and PSCI. This study investigated the effects of NBP on PSCI and secondary neurodegeneration in cynomolgus monkeys after permanent left middle cerebral artery occlusion (MCAO). METHODS: Thirteen adult male cynomolgus monkeys were randomly assigned to sham (n=4), MCAO+placebo (n=5), and MCAO+NBP groups (n=4). The MCAO+placebo and MCAO+NBP groups received saline and NBP injections intravenously, respectively, starting at 6-hour postsurgery for 2 weeks, followed by soybean oil and NBP orally, respectively, for 10 weeks after MCAO. Infarct size was assessed at week 4 by magnetic resonance imaging. Working memory and executive function were evaluated dynamically using the delayed response task and object retrieval detour task, respectively. Neuron loss, glia proliferation, and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex, thalamus, and hippocampus were analyzed by immunostaining 12 weeks after MCAO. RESULTS: Infarcts were located in the left middle cerebral artery region, apart from the ipsilateral dorsal lateral prefrontal cortex, thalamus, or hippocampus, with no significant difference between the MCAO+placebo and MCAO+NBP group. Higher success in delayed response task was achieved at weeks 4, 8, and 12 after NBP compared with placebo treatments (P<0.05), but not in the object retrieval detour task (all P>0.05). More neurons and less microglia, astrocytes, CD68-positive microglia, tumor necrosis factor-α, and inducible NO synthase were observed in the ipsilateral dorsal lateral prefrontal cortex and thalamus after 12 weeks of NBP treatment (P<0.05), but not in the hippocampus (P>0.05). CONCLUSIONS: Our findings indicate that NBP improves working memory by alleviating remote secondary neurodegeneration and neuroinflammation in the ipsilateral dorsal lateral prefrontal cortex and thalamus after MCAO in cynomolgus monkeys.

Identification of Cartilaginous Fish Endogenous Foamy Virus Rooting to Vertebrate Counterparts.

Foamy viruses (FVs) are ideal models for studying the long-term evolutionary history between viruses and their hosts. Currently, FVs have been documented in nearly all major taxa of vertebrates, but evidence is lacking for true FV infiltration in cartilaginous fish, the most basal living vertebrates with jaws. Here, we screened 11 available genomes and 10 transcriptome sequence assemblies of cartilaginous fish and revealed a novel endogenous foamy virus, termed cartilaginous fish endogenous foamy virus (CFEFV), in the genomes of sharks and rays. Genomic analysis of CFEFVs revealed feature motifs that were retained among canonical FVs. Phylogenetic analysis using polymerase sequences revealed the rooting nature of CFEFVs to vertebrate FVs, indicating their deep origin. Interestingly, three viral lineages were found in a shark (Scyliorhinus torazame), one of which was clustered with ray-finned fish foamy-like viruses, indicating that multiple episodes of viral infiltrations had occurred in this species. These findings fill a major gap in the Spumaretrovirinae taxon and reveal the aquatic origin of FVs found in terrestrial vertebrates. IMPORTANCE Although foamy viruses (FVs) have been found in major branches of vertebrates, the presence of these viruses in cartilaginous fish, the most basal living vertebrates with jaws, remains to be explored. This study revealed a collection of cartilaginous endogenous FVs in sharks and rays through in silico genomic mining. These viruses were rooted in the polymerase (POL) phylogeny, indicating the ancient aquatic origin of FVs. However, their envelope (ENV) protein grouped with those of amphibian FVs, suggesting different evolutionary histories of different FV genes. Overall, we provide the last missing gap for the taxonomic investigation of Spumaretrovirinae and provide concrete support for the aquatic origin of FVs.

Expansion and improvement of ChinaMu by MuT-seq and chromosome-level assembly of the Mu-starter genome.

ChinaMu is the largest sequence-indexed Mutator (Mu) transposon insertional library in maize (Zea mays). In this study, we made significant improvements to the size and quality of the ChinaMu library. We developed a new Mu-tag isolation method Mu-Tn5-seq (MuT-seq). Compared to the previous method used by ChinaMu, MuT-seq recovered 1/3 more germinal insertions, while requiring only about 1/14 of the sequencing volume and 1/5 of the experimental time. Using MuT-seq, we identified 113,879 germinal insertions from 3,168 Mu-active F1 families. We also assembled a high-quality genome for the Mu-active line Mu-starter, which harbors the initial active MuDR element and was used as the pollen donor for the mutation population. Using the Mu-starter genome, we recovered 33,662 (15.6%) additional germinal insertions in 3,244 (7.4%) genes in the Mu-starter line. The Mu-starter genome also improved the assignment of 117,689 (54.5%) germinal insertions. The newly upgraded ChinaMu dataset currently contains 215,889 high-quality germinal insertions. These insertions cover 32,224 pan-genes in the Mu-starter and B73Ref5 genomes, including 23,006 (80.4%) core genes shared by the two genomes. As a test model, we investigated Mu insertions in the pentatricopeptide repeat (PPR) superfamily, discovering insertions for 92% (449/487) of PPR genes in ChinaMu, demonstrating the usefulness of ChinaMu as a functional genomics resource for maize.

Evolution and Genetic Diversity of the Retroviral Envelope in Anamniotes.

Retroviruses are widely distributed in all vertebrates, as are their endogenous forms, endogenous retroviruses (ERV), which serve as "fossil" evidence to trace the ancient origins and history of virus-host interactions over millions of years. The retroviral envelope (Env) plays a significant role in host range determination, but major information on their genetic diversification and evolution in anamniotes is lacking. Here, by incorporating multiple-round in silico similarity search and phylogenomic analysis, more than 30,000 copies of ERV lineages with gamma-type Env (GTE), covalently associated Env, were discovered by searching against all fish and amphibian genomes and transcriptomic assemblies, but no beta-type Env (BTE), noncovalently associated Env, was found. Furthermore, a nine-type classification system of anamniote GTE was proposed by combining phylogenetic and domain/motif analyses. The elastic genomic organization and overall phylogenetic incongruence between anamniotic Env and its neighboring polymerase (Pol) implied that early retroviral diversification in anamniotic vertebrates was facilitated by frequent recombination. At last, host cellular opioid growth factor receptor (OGFr) gene capturing by anamniotic ERVs with GTE was reported for the first time. Overall, our findings overturn traditional Pol genotyping and reveal a complex evolutionary history of anamniotic retroviruses inferred by Env evolution. IMPORTANCE Although the retroviral envelope (Env) protein in amniotes has been well studied, its evolutionary history in anamniotic vertebrates is ambiguous. By analyzing more than 30,000 copies of ERV lineages with gamma-type Env (GTE) in anamniotes, several important evolutionary features were identified. First, GTE was found to be widely distributed among different amphibians and fish. Second, nine types of GTE were discovered and defined, revealing their great genetic diversity. Third, the incongruence between the Env and Pol phylogenies suggested that frequent recombination shaped the early evolution of anamniote retroviruses. Fourth, an ancient horizontal gene transfer event was discovered from anamniotes to ERVs with GTE. These findings reveal a complex evolution pattern for retroviral Env in anamniotes.

Predictions of optimal heating by magnetic reversal behavior of magnetic nanowires (MNWs) with different materials.

OBJECTIVE: Magnetic nanowires (MNWs) are potential candidates for heating in biomedical applications that require rapid and uniform heating rates, such as warming cryopreserved organs and hyperthermia treatment of cancer cells. Therefore, it is essential to determine which materials and geometries will provide the optimal heating using available alternating magnetic fields (AMF). METHOD: Micromagnetic simulations are used to investigate the heating ability of MNWs by predicting their hysteretic behavior. MNWs composed of iron (Fe), nickel (Ni), cobalt (Co) or permalloy (FeNi alloy, Py) with different diameters (10-200 nm) are simulated using object oriented micromagnetic framework (OOMMF). RESULTS: Hysteresis loops are obtained for each simulated MNW, and the 2D/3D magnetic moment map is simulated to show the reversal mechanism. The heating ability, in terms of specific loss power (SLP), is calculated from the area of the hysteresis loop times frequency for each MNW for comparison with others. CONCLUSION: It is estimated that a theoretical optimal heating ability of 2730 W/g can be provided by isolated Co MNWs with 50 nm diameters using a typical AMF system that can supply 72 kA/m field amplitude and 50 kHz in frequency. Generalized correlation between coercivity and size/material of MNWs is provided as a guidance for researchers to choose the most appropriate MNW as a heater for their AMF system and vice versa.

Multiple Infiltration and Cross-Species Transmission of Foamy Viruses across the Paleozoic to the Cenozoic Era.

Foamy viruses (FVs) are complex retroviruses that can infect humans and other animals. In this study, by integrating transcriptomic and genomic data, we discovered 412 FVs from 6 lineages in amphibians, which significantly increased the known set of FVs in amphibians. Among these lineages, salamander FVs maintained a coevolutionary pattern with their hosts that could be dated back to the Paleozoic era, while in contrast, frog FVs were much more likely acquired from cross-species (class-level) transmission in the Cenozoic era. In addition, we found that three distinct FV lineages had integrated into the genome of a salamander. Unexpectedly, we identified a lineage of endogenous FVs in caecilians that expressed all complete major genes, demonstrating the potential existence of an exogenous form of FV outside of mammals. Our discovery of rare phenomena in amphibian FVs has significantly increased our understanding of the macroevolution of the complex retrovirus. IMPORTANCE Foamy viruses (FVs) represent, more so than other viruses, the best model of coevolution between a virus and a host. This study represents the largest investigation so far of amphibian FVs and reveals 412 FVs of 6 distinct lineages from three major orders of amphibians. Besides a coevolutionary pattern, cross-species and repeated infections were also observed during the evolution of amphibian FVs. Remarkably, expressed FVs including a potential exogenous form were discovered, suggesting that active FVs might be underestimated in nature. These findings revealed that the multiple origins and complex evolution of amphibian FVs started from the Paleozoic era.

Glucose-6-phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients.

BACKGROUND AND PURPOSE: Intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke in Asian countries. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme defect prevalent in Asian countries, has been associated with atherosclerotic cardiovascular disease and worse poststroke outcomes. However, the impact of G6PD deficiency on ICAS remains unclear. We aimed to compare the risk of ICAS in stroke patients with and without G6PD deficiency in a Chinese cohort. METHODS: We prospectively and consecutively recruited stroke patients from four centers in China. All patients received intracranial artery assessment by magnetic resonance/computed tomography angiography or digital subtraction angiography, as well as G6PD enzyme evaluation. The prevalence, burden, and characteristics of ICAS were compared between patients with and without G6PD deficiency using multivariate regression analysis. RESULTS: Among 1593 patients, 116 (63.7%) of 182 patients with G6PD deficiency and 714 (50.6%) of 1411 patients with normal G6PD levels were identified as ICAS. Age, hypertension, diabetes, and G6PD deficiency were independent predictors of ICAS. Among patients with ICAS, G6PD-deficient individuals were more likely to have multiple (≥2 segments) intracranial stenosis (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.25-2.81, p = 0.002). G6PD deficiency increased the risk of ICAS in patients who were male (OR = 1.82, 95% CI = 1.24-2.66, p = 0.002), aged ≥70 years (OR = 2.40, 95% CI = 1.33-4.31, p = 0.004), or hypertensive (OR = 1.88, 95% CI = 1.28-2.77, p = 0.001). CONCLUSIONS: Stroke patients with G6PD deficiency have a higher prevalence and ICAS burden than those with normal G6PD, particularly those who are male, older, and hypertensive.

High on-treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta-analysis.

OBJECTIVES: High on-treatment platelet reactivity (HTPR) determined by platelet function assays is present in certain patients with ischemic stroke or transient ischemic attack (TIA). However, it is unclear whether HTPR is associated with poor clinical outcomes. Our study aimed to investigate the relationship of HTPR with recurrent vascular events in ischemic stroke or TIA. METHODS: Pubmed (MEDLINE), EMBASE, and Cochrane Library were searched for eligible studies from inception to January 1, 2022. Stata 17.0 software was used to calculate the risk ratio (RR). Subgroup and sensitivity analyses were conducted to assess the source of heterogeneity. A random-effects model was used when heterogeneity was present. Primary endpoint of the meta-analysis was the risk ratio of recurrent vascular events in HTPR Patients. While stroke and TIA, all-cause death, early neurological deterioration, early new ischemic lesions, and stroke severity measured by National Institute of Health Stroke Scale (NIHSS) scores at admission were also pooled. RESULTS: Thirty articles (7995 patients) were eligible including 28 cohort studies and 2 prospective case-control studies. The prevalence of HTPR varied from 5.9% to 60%. HTPR was associated with an increased risk of recurrent vascular events (RR = 2.94, 95% CI 2.04-4.23), stroke recurrence (RR = 2.05; 95% CI 1.43-2.95), and all-cause mortality (RR = 2.43; 95% CI 1.83-3.22). Subgroup analysis showed that HTPR determined by optical aggregometry, Verify-Now system and 11dh TXB2 is related to a higher risk of recurrent vascular events (RR = 3.53, 95% CI 1.51-9.40; RR = 2.16, 95% CI 1.02-4.56; RR = 3.76, 95% CI 1.51-9.40, respectively). Moreover, patients with HTPR had an increased incidence of early neurological deterioration (RR = 2.75; 95% CI 1.76-4.30) and higher NIHSS scores at admission (Mean difference 0.19, 95% CI 0.01-0.36). CONCLUSIONS: This meta-analysis demonstrates HTPR is associated with higher risk of recurrent vascular events, early neurological deterioration and increased severity in patients with ischemic stroke and TIA. HTPR measured by platelet function assays may guide the use of antiplatelet agents in ischemic stroke and TIA.

Bioapplications of Magnetic Nanowires: Barcodes, Biocomposites, Heaters.

Magnetic nanowires (MNWs) can have their moments reversed via several mechanisms that are controlled using the composition, length, diameter, and density of nanowires in arrays as-synthesized or as individual nanoparticles in assays or gels. This tailoring of magnetic reversal leads to unique properties that can be used as a signature for reading out the type of MNW for applications as nano-barcodes. When synthesized inside track-etched polycarbonate membranes, the resulting MNW-embedded membranes can be used as biocompatible bandaids for detection without contact or optical sighting. When etched out of the growth template, free-floating MNWs are internalized by cells at 37 °C such that cells and/or exosomes can be collected and detected. In applications of cryopreservation, MNWs can be suspended in cryopreservation agents (CPAs) for injection into the blood vessels of tissues and organs as they are vitrified to -200 °C. Using an alternating magnetic field, the MNWs can then be nanowarmed rapidly to prevent crystallization and uniformly to prevent cracking of specimens, for example, as grafts or transplants. This invited paper is a review of recent progress in the specific bioapplications of MNWs to barcodes, biocomposites, and nanowarmers.

Efficient adsorption of diclofenac sodium in water by a novel functionalized cellulose aerogel.

In this work, a novel cellulose aerogel (CNC-PVAm/rGO) was fabricated using cellulose nanocrystalline (CNC) modified with polyvinylamine (PVAm) and reduced graphene oxide (rGO). The resultant CNC-PVAm/rGO was then applied for the adsorption of diclofenac sodium (DCF), a typical non-steroidal anti-inflammatory drug. Characterization using ultra-high-resolution field emission scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and the Brunauer-Emmett-Teller surface area revealed that the obtained CNC-PVAm/rGO displayed an evident 3D porous structure, which had an ultralight weight, good recovery, abundant surface functional groups (e.g., -NH2 and -OH), and rGO nanosheets. In addition, the material presented a stable crystal structure and large specific surface area (105.73 m2 g-1). During the adsorption of DCF, the CNC-PVAm/rGO aerogel showed a rather excellent adsorption performance, with a maximum adsorption capacity (qmax) of 605.87 mg g-1, which was approximately 53 times larger than that of the bare CNC aerogel (11.45 mg g-1). The adsorption performance of CNC-PVAm/rGO was also better than that of other reported adsorbents. The adsorption of DCF to CNC-PVAm/rGO obeyed the Langmuir isotherm and pseudo-second-order kinetic models, and underwent a spontaneous exothermic process. Moreover, DCF was easily desorbed from CNC-PVAm/rGO with sodium hydroxide solution (0.1 mol L-1), and the absorbent could be reused four times. The introduction of PVAm and rGO to the CNC-PVAm/rGO aerogel also greatly enhanced electrostatic interactions, π-π interactions, and hydrophobic effects. These enhancements significantly promoted the hydrogen bonding interactions between the DCF molecules and CNC-PVAm/rGO, thus resulting in a large improvement in the adsorption performance of the aerogel.

Association between socioeconomic status and post-stroke functional outcome in deprived rural southern China: a population-based study.

BACKGROUND: Data on the association between socioeconomic status and post-stroke functional outcome in developing countries is lacking. We aimed to evaluate the association in stroke survivors in deprived rural Southern China. METHODS: We conducted door-to-door interviews and collected data using a structured questionnaire in stroke survivors from five fourth-class rural areas of Guangdong Province through a non-government initiated registry from August 2014 to March 2015. Descriptive statistics were used to provide information on the demographic, socioeconomic and clinical characteristics of the selected population. Univariate and multivariate logistic regression were used to examine the relationship of socioeconomic status indexed by self-reported average family income and functional impairment defined as a modified Rankin Scale of 3 to 5. RESULTS: Among the 425 stroke survivors, 52.7% lived below the poverty line set by the local government. About 50% of patients suffered from functional impairment and required assistance in their daily life. Compared with their wealthier counterpart, stroke survivors with lower income were more likely to have functional impairment (OR 2.85, 95% CI 1.93-4.23). The effect size increased and remained significant after adjusting for possible confounding factors (OR 3.17, 95% CI 2.04-4.91). CONCLUSIONS: Poorer patients tend to have poorer post-stroke functional outcome. Primary and secondary strategies targeting underprivileged populations in less-developed areas are thus urgently needed in China.

Pillared graphite anodes for reversible sodiation.

There has been a major effort recently to develop new rechargeable sodium-ion electrodes. In lithium ion batteries, LiC6 forms from graphite and desolvated Li cations during the first charge. With sodium ions, graphite only shows a significant capacity when Na+ intercalates as a solvated complex, resulting in ternary graphite intercalation compounds (GICs). Although this chemistry has been shown to be highly reversible and to support high rates in small test cells, these GICs can require >250% volume expansion and contraction during cycling. Here we demonstrate the first example of GICs that reversibly sodiate/desodiate without any significant volume change. These pillared GICs are obtained by electrochemical reduction of graphite in an ether/amine co-solvent electrolyte. The initial gallery expansion, 0.36 nm, is less than half of that in diglyme-based systems, and shows a similar capacity. Thermal analyses suggest the pillaring phenomenon arises from stronger co-intercalate interactions in the GIC galleries.

2-Cl-MGV-1 Ameliorates Apoptosis in the Thalamus and Hippocampus and Cognitive Deficits After Cortical Infarct in Rats.

BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl) quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction. METHODS: One hundred fourteen hypertensive rats underwent successful distal middle cerebral artery occlusion (n=76) or sham procedures (n=38). 2-Cl-MGV-1 or dimethyl sulfoxide as vehicle was administrated 2 hours after distal middle cerebral artery occlusion and then for 6 or 13 days (n=19 per group). Spatial learning and memory were tested using the Morris water maze. Secondary degeneration and mitochondrial apoptosis in the thalamus and hippocampus were assessed using Nissl staining, immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling, JC-1 staining, and immunoblotting 7 and 14 days after surgery. RESULTS: Infarct volumes did not significantly differ between the vehicle and 2-Cl-MGV-1 groups. There were more neurons and fewer glia in the ipsilateral thalamus and hippocampus in the vehicle groups than in the sham-operated group 7 and 14 days post-distal middle cerebral artery occlusion. 2-Cl-MGV-1 significantly ameliorated spatial cognitive impairment and decreased neuronal death and glial activation when compared with vehicle treatment (P<0.05). The collapse of mitochondrial transmembrane potential and cytoplasmic release of apoptosis-inducing factors and cytochrome c was prevented within the thalamus. Caspase cleavage and the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling+ or Nissl atrophic cells were reduced within the thalamus and hippocampus. This was accompanied by upregulation of B-cell lymphoma 2 and downregulation of Bax (P<0.05). CONCLUSIONS: 2-Cl-MGV-1 reduces neuronal apoptosis via mitochondrial-dependent pathways and attenuates secondary damage in the nonischemic thalamus and hippocampus, potentially contributing to ameliorated cognitive deficits after cortical infarction.

Weakness of Eye Closure with Central Facial Paralysis after Unilateral Hemispheric Stroke Predicts a Worse Outcome.

BACKGROUND: Upper facial dysfunction is not generally considered a feature of central facial paralysis after unilateral hemispheric stroke; however, weakness of eye closure (WEC) has been observed in some cases. We aimed to investigate the frequency and characteristics of WEC in unilateral stroke and its association with stroke prognosis. METHODS: Patients with unilateral stroke and central facial paralysis were prospectively recruited within 7 days of onset. Facial paralysis was evaluated via the fourth item in the National Institute of Health Stroke Scale (NIHSS-4) and the Japan Facial Score (JFS) on admission, and at days 7, 14, 21, and 30 after stroke. Eye closure strength was measured daily using an ergometer for 30 days after stroke. Primary outcome was assessed using the modified Rankin Scale (mRS) at 90 and 180 days. Univariate and multivariate analyses were performed to investigate risk factors of WEC. RESULTS: WEC was identified in 16 of 242 patients (6.6%). Baseline characteristics, stroke risk factors, and lesion volume were not significantly different between patients with and patients without WEC. Patients with WEC featured higher NIHSS-4 scores and lower JFS between admission and at 21 days after stroke. Severe central facial paralysis (odds ratio [OR] = 8.1, 95% confidence interval [CI] = 2.3-28.6, P = .001) and right hemispheric stroke (OR = 13.7, 95% CI = 3.7-51.2, P < .001) were potential predictors of WEC. At 180 days after stroke, patients with WEC demonstrated a lower rate of functional independence (mRS = 0-2: 37.5% versus 72.1%, P < .001). CONCLUSIONS: WEC, which predicts a worse functional outcome at 180 days after unilateral stroke, demonstrates an association with severe central facial paralysis and right hemispheric stroke.

Late-onset aspirin-related hemolysis and subsequent subdural hemorrhage in patient with glucose-6-phosphate dehydrogenase deficiency.

Key Clinical Message: Aspirin-related hemolysis in G6PD deficiency could be late-onset during long-term administration. Hemolytic anemia could continue for a relatively long time in elder patient with G6PD deficiency, which might be related to other adverse events. Abstract: Aspirin-related hemolysis in G6PD-deficient individuals was generally reported among patients who received high-dose supplements within several days after ingestion. The safety of long-term and low-dose (50-325 mg/day) aspirin in patients coexist G6PD deficiency and cardiovascular disease is neglected in clinical practice. In this case, we observed a late-onset hemolysis and subsequent fatal subdural hemorrhage in one G6PD-deficient individual who had received long-term and low-dose aspirin. An 83-year-old male was diagnosed with acute ischemic stroke and treated with 100 mg/day aspirin at the emergency room. After admission, the patient was diagnosed with severe G6PD deficiency based on enzyme activity, but no hemolysis occurred within 10-day aspirin therapy in the hospital. Hence, 100 mg/day aspirin was continued on discharge. Two months later, the patient presented acute hemolysis manifested as fatigue, dark urine, and moderate jaundice. Although hemolysis was self-limit in a few days, hemoglobin decline continued for 20 days until a fatal subdural hemorrhage occurred. Our study indicated aspirin-related hemolysis could be late-onset in G6PD-deficient individual even receiving low-dose treatment and is probably linked to subsequent major bleeding events.

Enhanced angiogenesis in the thalamus induced by a novel TSPO ligand ameliorates cognitive deficits after focal cortical infarction.

Neuronal loss in the ipsilateral thalamus after focal cortical infarction participates in post-stroke cognitive deficits, and enhanced angiogenesis in the thalamus is expected to reduce neuronal damage. We hypothesize that novel translocator protein (TSPO) ligand, 2-Cl-MGV-1, can promote angiogenesis, attenuate neuronal loss in the thalamus, and ameliorate post-stroke cognitive deficits. Cortical infarction was induced by distal middle cerebral artery occlusion (dMCAO) in stroke-prone renovascular hypertensive rats. 2-Cl-MGV-1 or dimethyl sulfoxide was administered 24 h after dMCAO and then for 6 or 13 days. Spatial learning and memory were assessed using the Morris water maze. Neuronal loss, TSPO expression, angiogenesis, and intrinsic pathway were determined by immunofluorescence and immunoblotting 7 and 14 days after dMCAO. Cortical infarction caused post-stroke cognitive deficits and secondary neuronal loss with gliosis in the ipsilateral thalamus within 14 days of dMCAO. Increased angiogenesis and elevated expression of vascular TSPO were detected in the ipsilateral thalamus, and treatment with 2-Cl-MGV-1 enhanced angiogenesis by stimulating the PI3K-AKT-mTOR pathway. The effects of 2-Cl-MGV-1 on angiogenesis coincided with reduced neuronal loss in the thalamus and contributed to improvements in post-stroke cognitive deficits. Our findings suggest that 2-Cl-MGV-1 stimulates angiogenesis, ameliorates neuronal loss in the thalamus, and improves post-stroke cognitive deficits.

Efficacy and safety of agomelatine versus SSRIs/SNRIs for post-stroke depression: a systematic review and meta-analysis of randomized controlled trials.

Agomelatine is effective in the treatment of depression, but its effect for post-stroke depression (PSD) remains unclear. This study was conducted to compare the efficacy and safety of agomelatine versus SSRIs/SNRIs in treating PSD. We systematically searched Embase, PubMed, Cochrane Library, WanFang Data, China National Knowledge Infrastructure, and Cqvip databases for double-blind randomized controlled studies comparing the efficacy and safety of agomelatine versus SSRIs/SNRIs for PSD until December 2022. The primary efficacy endpoint was the Hamilton Depression Rating Scale (HAMD) score, and the primary safety endpoint was the incidence of overall adverse reactions. Nine studies comprising 857 patients with PSD were included. After 6-12 weeks of treatment, the HAMD score ( P  = 0.16) and the overall response rates ( P  = 0.20) in the agomelatine group were comparable to that in the SSRIs/SNRIs group. Participants treated with agomelatine achieved higher Barthel Index scores compared with the SSRIs/SNRIs group ( P  = 0.02). There was a significantly lower incidence of overall adverse reactions ( P  = 0.008) and neurological adverse reactions ( P  < 0.0001) in the agomelatine group. The efficacy of agomelatine for treating PSD is probably comparable to that of SSRIs/SNRIs, and it may improve stroke outcomes with better safety.

Pattern of cooling benefits from ecospaces during urbanization: A case study of the Yangtze River Economic Belt.

Urban ecological spaces are effective thermoregulators under global warming. However, the cooling efficiency of urban ecological spaces during the urbanization has not been studied comprehensively. Here, we investigate the spatio-temporal dynamics of Urban Cold Island (UCI) intensity in 11 typical cities of the Yangtze River Economic Belt (YREB). We determined the impact of ecological landscape trends on these dynamics by using GlobalLand and MODIS 8 d mean land surface temperature (LST) data for three periods (2000, 2010, and 2020), and the landscape pattern index and diversity index. We found that in the past 20 years, the built-up area has increased by sixfold; 62.53 % and 37.47 % of YREB were warming or cooling, with 71.22 % of the daytime cooling and 93 % of the nighttime warming. The average UCI intensity of YREB has increased from 0.518 to 0.847 and is negatively correlated with LST with a decreasing slope. As the UCI intensity of green spaces increased, that of blue spaces decreased. Surface area and landscape pattern are the key determinants of UCI intensity in blue and green spaces, respectively, especially the landscape shape index (LSI). Therefore, maintaining ecological spaces, enriching the structural integrity of green spaces, and improving blue space connectivity can help cities at different development levels cope with heat stress during regional urbanization.

Pulmonary blastoma is successfully treated with immunotherapy and targeted therapy.

Pulmonary blastomas (PB) are an extremely rare type of lung cancer. Currently, no standard treatment exists for PB. Immunotherapy with checkpoint inhibitors and anti-angiogenesis treatments has been an effective method for lung cancer; however, studies on PB treatment are lacking. Herein, we present a case report of successful conversion therapy with immunotherapy and targeted therapy for PB. After receiving treatment with a PD-1 inhibitor (penpulimab) and a multi-target tyrosine kinase inhibitor (anlotinib) treatment, the patient showed an impressive response and underwent a successful operation. We also summarized and reviewed literature reports on PubMed from January 1, 2000, to December 31, 2022, using the keyword "pulmonary blastoma", discussing the efficacy and specifics of chemotherapy and radiotherapy. Immunotherapy, in combination with targeted therapy, should be considered a potential therapeutic strategy for PB.

Certification of stroke centers at primary hospitals and the improvement of thrombolysis n South China during 2020-2022.

INTRODUCTION: IVT use declined globally in 2020 due to the Corona Virus Disease 2019 (COVID-19) pandemic, but it increased in South China. This study was conducted to evaluate the association of establishing Stroke Prevention Centers (SPCs) at primary hospitals with IVT increase in South China. MATERIALS AND METHODS: We conducted a longitudinal observational study across 336 hospitals in 114 areas in South China during 2020-2022. Data regarding certified stroke centers, IVT volumes, and IVT rates were collected. Correlations between IVT rates and the number or density of stroke centers were accessed. IVT use was compared among areas with different levels of stroke centers or on different certification process. RESULTS: During 2020-2022, there were 83, 125, and 152 stroke centers, with 26, 65, and 92 SPCs, respectively. IVT therapies were 12,795, 17,266, and 20,411, representing a 29.8% increase/year (all p < 0.001). IVT rates increased from 7.2% in 2020 to 8.8% and 10.4% in 2021 and 2022, demonstrating a 22.2% increase/year (all p < 0.001). IVT rates correlated with the number and density of SPCs (all p < 0.05). IVT rates were higher in areas equipped with SPCs than in those without stroke centers (all p < 0.05). IVT rates consistently increased during the SPC certification process from 1 year before through the certification and subsequent maintenance (both p < 0.05). DISCUSSION AND CONCLUSION: Well-organised SPCs and IVT therapy demonstrated substantial increase during the 3-year period. Certification of SPCs at primary hospitals is associated with improved IVT therapy in South China even with city lockdown during COVID-19 pandemic.