Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Efficacy and Mechanism Study of 6S-5-Methyltetrahydrofolate-Calcium Against Telencephalon Infarction Injury in Zebrafish Model of Ischemic Stroke.

Ischemic stroke is a heterogeneous brain injury with complex pathophysiology and it is also a time sensitive neurological injury disease. At present, the treatment options for ischemic stroke are still limited. 6S-5-methyltetrahydrofolate-calcium (MTHF-Ca) is the calcium salt of the predominant form of dietary folate in circulation. MTHF-Ca has potential neuroprotective effect on neurocytes, but whether it can be used for ischemic stroke treatment remains unknown. We established zebrafish ischemic stroke model through photothrombotic method to evaluate the protective effect of MTHF-Ca on the ischemic brain injury of zebrafish. We demonstrated that MTHF-Ca reduced the brain damage by reducing motor dysfunction and neurobehavioral defects of zebrafish with telencephalon infarction injury. MTHF-Ca counteracted oxidative damages after Tel injury by increasing the activities of GSH-Px and SOD and decreasing the content of MDA. RNA-seq and RT-qPCR results showed that MTHF-Ca played a neuroprotective role by alleviating neuroinflammation, inhibiting blood coagulation, and neuronal apoptosis processes. Overall, we have demonstrated that MTHF-Ca has neuroprotective effect in ischemic stroke and can be used as a potential treatment for ischemic stroke.

Clinical, Imaging Characteristics and Outcome of Intracerebral Hemorrhage Caused by Structural Vascular Lesions.

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

Dengue and Zika RNA-RNA interactomes reveal pro- and anti-viral RNA in human cells.

BACKGROUND: Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. RESULTS: Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3'UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3'UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. CONCLUSIONS: This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.

Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

Evaluating the internalisation of the intrinsic role of health advocacy of student pharmacists in a new integrated Bachelor of Pharmacy curriculum: a mixed-methods study.

To keep up with the contemporary health landscape, there is an imperative need for healthcare professionals to practise health advocacy through health promotion on the individual, population, and systems levels. In the Academic Year of 2020/2021, the National University of Singapore (NUS) Department of Pharmacy implemented a new spiral curriculum integrating basic, clinical, and systems sciences with one of its aims to deepen students' health advocacy internalisation and prepare them as future health advocates. A mixed-methods approach was adopted. Questionnaires were disseminated across three time-points to elicit students' levels of internalisation of health advocacy, which were then categorised into levels, and a Mann-Whitney U test was conducted. In comparison with prematriculation, no significant difference was found after students underwent the first year of the curriculum, while a significant difference was found after students underwent two years of the curriculum. Semi-structured interviews were also conducted after each Academic Year to gain deeper insights into the questionnaire results. Thematic analysis of the interviews revealed that curricular integration in the first year was perceived to be lacking. However, with learnt knowledge constantly reinforced and more experiential learning opportunities incorporated throughout the second year, students found the integrated curriculum beneficial in instilling confidence to practise health advocacy. This study offers insights into the prospects of a spiral integrated curriculum in imparting health advocacy, and may even suggest its potential to be applied to other educational settings. Future follow-up studies can also be conducted on the same study population to evaluate long-term impacts and areas for improvement of the curriculum.

Ultraearly Intraventricular Hemorrhage Growth Predicts Early Neurologic Deterioration and Poor Functional Outcome After Acute Intracerebral Hemorrhage.

Background The presence of intraventricular hemorrhage (IVH) was extensively investigated and was associated with poor outcome in patients with intracerebral hemorrhage (ICH). However, the effect of the speed of ventricular bleeding on outcomes is unknown. Methods and Results We prospectively included patients with ICH who had baseline computed tomography scans within 6 hours after ictus between January 2016 and October 2021. The clinical characteristics were compared between patients with and without early neurologic deterioration (END). Ultraearly IVH growth (uIVHG) was defined as baseline IVH volume by onset-to-imaging time. The association between uIVHG and outcomes was assessed by using multivariable logistic regression analysis. We established the ultraearly IVH growth (uIVH) score and compared the areas under the receiver operating characteristic curves of the existing scores for predicting END. A total of 299 patients were finally enrolled. Of those, 38 patients (12.7%) experienced END at 24 hours and 89 patients (29.8%) had poor outcomes at 90 days. After adjustment for confounding factors, uIVHG (odds ratio, 1.061 [95% CI, 1.011-1.113]; P=0.016) was independently associated with END in multivariable analysis. A prediction score was developed on the basis of the logistic model. The uIVH score was developed as a sum of individual points (0-6) based on age, hematoma volume, National Institutes of Health Stroke Scale, hematoma expansion, and uIVHG ≥2.5 mL/h. In comparison with the ICH score and modified Emergency Department ICH Scale, the uIVH score exhibited best performance in the prediction of END. Conclusions uIVHG is associated with early neurologic deterioration and poor functional outcome in patients with ICH.

Memory Trace for Fear Extinction: Fragile yet Reinforceable.

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement, allowing the organism to re-adapt to ever-changing situations. Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory, this new memory is more readily forgettable than the original fear memory. The brain's cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear. Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory. In this review, we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction, aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

Blood-Based Biomarkers in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most lethal subtypes of stroke, associated with high morbidity and mortality. Prevention of hematoma growth and perihematomal edema expansion are promising therapeutic targets currently under investigation. Despite recent improvements in the management of ICH, the ideal treatments are still to be determined. Early stratification and triage of ICH patients enable the adjustment of the standard of care in keeping with the personalized medicine principles. In recent years, research efforts have been concentrated on the development and validation of blood-based biomarkers. The benefit of looking for blood candidate markers is obvious because of their acceptance in terms of sample collection by the general population compared to any other body fluid. Given their ease of accessibility in clinical practice, blood-based biomarkers have been widely used as potential diagnostic, predictive, and prognostic markers. This review identifies some relevant and potentially promising blood biomarkers for ICH. These blood-based markers are summarized by their roles in clinical practice. Well-designed and large-scale studies are required to validate the use of all these biomarkers in the future.

Incidence, characteristics and outcome of post-stroke recrudescence in the Chinese population: a single-centre observational study.

OBJECTIVES: The aim of our observational study was to investigate the incidence, clinical characteristics and outcome of post-stroke recrudescence (PSR) in the Chinese population. DESIGN AND SETTING: Single-centre prospective observational study in China. PARTICIPANTS: A total of 1114 patients who had a suspected stroke were prospectively screened from October 2020 to February 2022. OUTCOME MEASURES: The primary outcome was the proportion of patients with functional independence defined as a score of 0-2 on the modified Rankin Scale (mRS) at 3 months. Secondary outcomes were: early neurological improvement (ENI), defined as a National Institutes of Health Stroke Scale (NIHSS) score of 0 or an improvement of ≥2 points from admission at 24 hours; mortality within 3 months; stroke recurrence within 3 months and length of stay in hospital. RESULTS: A total of 959 patients with cerebral infarction and 30 patients without an available magnetic resonance imaging (MRI) scan were excluded. Among the 125 included patients, 27 cases of PSR (2.4%), 50 cases of transient ischaemic attack (TIA) (4.5%) and 48 cases of stroke mimics (SMs) (4.3%) were identified. A higher frequency of infection at admission (22.2% vs 2%, p=0.007) was observed in patients with PSR compared with patients with TIA, and a lower proportion of functional independence at 3 months (80% vs 98%, p=0.015) was seen. Patients with TIA had a higher frequency of ENI compared with patients with PSR and SMs (98% vs 59.3%, p<0.001; 98% vs 52.1%, p<0.001). Patients with PSR exhibited a higher frequency of grade 2 Fazekas deep white matter hyperintensity compared with those with SMs (33.3% vs 8.3%, p=0.010). CONCLUSIONS: PSR is not uncommon in patients presenting with stroke symptoms and can be distinguished from TIA and SMs based on a combination of clinical features and trigger in the Chinese population. The neurological deficits of patients with PSR often resolve within several days following the resolution of the trigger.

Controlled Growth of Highly Oriented Perovskite Crystals in Polymer Solutions via Selective Solvent Vapor Diffusion.

Organic-inorganic hybrid perovskites have garnered significant attention in optoelectronics owing to their outstanding tunable optical characteristics. Controlled growth of perovskite nanocrystals from solutions is key for controlling the emission intensity and photoluminescence lifetime of perovskites. In particular, most studies have focused on controlling the crystallization of perovskite through chemical treatment using chelating ligands or physical treatment via antisolvent diffusion, and there exists a trade-off between the photoluminescence intensity and lifetime of perovskites. Herein, a selective solvent vapor-assisted crystallization with the aid of a functional polymer, which nanoscale perovskite crystals are grown andante from precursor solution, is presented for tuning the crystallization and optical properties of a common halide perovskite, methylammonium lead bromide (MAPbBr3 ). The proposed method here produces perovskite nanocrystals in the range of 200-300 nm. The spin-coated thin film formed from the perovskite solution exhibits strong green photoluminescence with a long lifetime. The effects of the functional group and polymer dosage on the crystallization of MAPbBr3 are systematically investigated, and the crystallization mechanism is explained based on a modified LaMer model. This study provides an advanced solution process for precisely controlling perovskite crystallization to enhance their optical properties for next-generation optoelectronic devices.

Discovery and biological evaluation of a new type of dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase from ethnomedicinal plant Dactylicapnos scandens.

The root of Dactylicapnos scandens (D.Don.) Hutch (Papaveraceae), one of the most famous ethno-medicinal plants from the Bai communities in P. R. China, is used to treat various inflammations and tumours. Bioassay-guided phytochemical research on D. scandens followed by semi-synthesis led to a series of undescribed tetrahydroisoquinoline alkaloids with dual inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). The previously undescribed dark-green alkaloid dactycapnine A exhibited the best dual inhibitor effects among the identified compounds. Structure-activity relationship analysis revealed the importance of the base skeleton with a hyperconjugation system. The performed semi-synthesis further yielded bioactive dimeric and trimeric compounds with hyperconjugated systems. Performed STD NMR experiments disclosed direct interactions between dactycapnine A and IDO1/TDO. Inhibition kinetics indicated dactycapnine A as a mixed-type dual inhibitor. These findings provided a possible explanation for the anticancer properties of the ethno-medicinal plant species D. scandens.

Anti-inflammatory effects of 6S-5-methyltetrahydrofolate-calcium on RAW264.7 cells and zebrafish.

AIM: 6S-5-methyltetrahydrofolate is the predominant form of dietary folate in circulation and is used as a crystalline form of calcium salt (MTHF-Ca). Reports revealed that MTHF-Ca was more safe than folic acid, a synthetic and highly stable version of folate. Folic acid has been reported to have anti-inflammatory effects. The study's objective was to assess the anti-inflammatory effect of MTHF-Ca in vitro and in vivo. MAIN METHODS: In vitro, the ROS production was assessed by H2DCFDA, and nuclear translocation of NF-κB were evaluated by the NF-κB nuclear translocation assay kit. Interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. In vivo, ROS production was assessed by H2DCFDA, neutrophils and macrophages recruitment were evaluated in tail transection-induced and CuSO4-induced zebrafish inflammation models. Expression of inflammation related genes were also investigated based on CuSO4-induced zebrafish inflammation model. KEY FINDINGS: MTHF-Ca treatment decreased LPS-induced ROS production, inhibited nuclear translocation of NF-κB and decreased the levels of IL-6, IL-1ß and TNF-α in RAW264.7 cells. In addition, MTHF-Ca treatment inhibited ROS production, suppressed the recruitment of neutrophils and macrophages, and reduced the expression of inflammation related genes, including jnk, erk, nf-κb, myd88, p65, tnf-α, and il-1b in zebrafish larvae. SIGNIFICANCE: MTHF-Ca may play an anti-inflammatory role by reducing the recruitment of neutrophils and macrophages and keeping the low levels of proinflammatory mediators and cytokines. MTHF-Ca may have a potential role in the treatment of inflammatory diseases.

Divergent functions of histone acetyltransferases KAT2A and KAT2B in keratinocyte self-renewal and differentiation.

The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.

Neutrophil percentage to albumin ratio is associated with stroke-associated pneumonia and poor outcome in patients with spontaneous intracerebral hemorrhage.

Background: The purpose of this study was to investigate the diagnostic performance of the neutrophil percentage-to-albumin ratio (NPAR) for predicting stroke-associated pneumonia (SAP) and functional outcome in patients with intracerebral hemorrhage (ICH). Methods: We analyzed our prospective database of consecutive ICH patients who were admitted to the First Affiliated Hospital of Chongqing Medical University from January 2016 to September 2021. We included subjects with a baseline computed tomography available and a complete NPAR count performed within 6h of onset. The patients' demographic and radiological characteristics were analyzed. Good outcome was defined as a modifed Rankin Scale score of 0-3 at 90 days. Poor outcome was defined as a modifed Rankin Scale score of 4-6 at 90 days. Multivariable logistic regression models were used to investigate the association between NPAR, SAP, and functional outcome. Receiver operating characteristic (ROC) curve analysis was conducted to identify the optimal cutoff of NPAR to discriminate between good and poor outcomes in ICH patients. Results: A total of 918 patients with ICH confirmed by non-contrast computed tomography were included. Of those, 316 (34.4%) had SAP, and 258 (28.1%) had poor outcomes. Multivariate regression analysis showed that higher NPAR on admission was an independent predictor of SAP (adjusted odds ratio: 2.45; 95% confidence interval, 1.56-3.84; P<0.001) and was associated with increased risk of poor outcome (adjusted odd ratio:1.72; 95% confidence interval, 1.03-2.90; P=0.040) in patients with ICH. In ROC analysis, an NPAR of 2 was identified as the optimal cutoff value to discriminate between good and poor functional outcomes. Conclusion: Higher NPAR is independently associated with SAP and poor functional outcome in patients with ICH. Our findings suggest that early prediction of SAP is feasible by using a simple biomarker NPAR.

Dengue Virus Capsid Protein Facilitates Genome Compaction and Packaging.

Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigated the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrated that C protein interaction with DENV genomes saturates at an RNA:C protein ratio below 1:250. Moreover, we also showed that the length of the RNA genome interaction sites varies, in a multimodal distribution, consistent with the C protein binding to each RNA site mostly in singlets or pairs (and, in some instances, higher numbers). We showed that interaction sites are preferentially sites with low base pairing, as previously measured by 2'-acetylation analyzed by primer extension (SHAPE) reactivity indicating structuredness. We found a clear association pattern emerged: RNA-C protein binding sites are strongly associated with long-range RNA-RNA interaction sites, particularly inside virions. This, in turn, explains the need for C protein in viral genome packaging: the protein has a chief role in coordinating these key interactions, promoting proper packaging of viral RNA. Such sites are, thus, highly consequential for viral assembly, and, as such, may be targeted in future drug development strategies against these and related viruses.

Comparison of different noncontrast computed tomographic markers for predicting early perihematomal edema expansion in patients with intracerebral hemorrhage.

OBJECTIVES: Noncontrast computed tomography (NCCT) imaging markers are associated with early perihematomal edema (PHE) growth. The aim of this study was to compare the predictive value of different NCCT markers in predicting early PHE expansion. METHODS: ICH patients who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan within 36 h between July 2011 and March 2017 were included in this study. The predictive value of hypodensity, satellite sign, heterogeneous density, irregular shape, blend sign, black hole sign, island sign and expansion-prone hematoma for early perihematomal edema expansion were assessed, separately. RESULTS: 214 patients were included in our final analysis. After adjusting for ICH characteristics, hypodensity, blend sign, island sign and expansion-prone hematoma are still predictors of early perihematomal edema expansion in multivariable logistics regression analysis (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of expansion-prone hematoma was significantly larger than the area under the ROC curve of hypodensity, blend sign and island sign in predicting PHE expansion (P = 0.003, P < 0.001 and P = 0.002, respectively). CONCLUSION: Compared with single NCCT imaging markers, expansion-prone hematoma seems to be optimal predictor for early PHE expansion than any single NCCT imaging marker.