Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

Cross-patch feature interactive net with edge refinement for retinal vessel segmentation.

Retinal vessel segmentation based on deep learning is an important auxiliary method for assisting clinical doctors in diagnosing retinal diseases. However, existing methods often produce mis-segmentation when dealing with low contrast images and thin blood vessels, which affects the continuity and integrity of the vessel skeleton. In addition, existing deep learning methods tend to lose a lot of detailed information during training, which affects the accuracy of segmentation. To address these issues, we propose a novel dual-decoder based Cross-patch Feature Interactive Net with Edge Refinement (CFI-Net) for end-to-end retinal vessel segmentation. In the encoder part, a joint refinement down-sampling method (JRDM) is proposed to compress feature information in the process of reducing image size, so as to reduce the loss of thin vessels and vessel edge information during the encoding process. In the decoder part, we adopt a dual-path model based on edge detection, and propose a Cross-patch Interactive Attention Mechanism (CIAM) in the main path to enhancing multi-scale spatial channel features and transferring cross-spatial information. Consequently, it improve the network's ability to segment complete and continuous vessel skeletons, reducing vessel segmentation fractures. Finally, the Adaptive Spatial Context Guide Method (ASCGM) is proposed to fuse the prediction results of the two decoder paths, which enhances segmentation details while removing part of the background noise. We evaluated our model on two retinal image datasets and one coronary angiography dataset, achieving outstanding performance in segmentation comprehensive assessment metrics such as AUC and CAL. The experimental results showed that the proposed CFI-Net has superior segmentation performance compared with other existing methods, especially for thin vessels and vessel edges. The code is available at https://github.com/kita0420/CFI-Net.

Being close or being alone: How Social ostracism affects solitude preference.

Social ostracism refers to the phenomenon of being excluded from social interactions and not being accepted by society. While previous research has examined its impact on prosocial and antisocial behaviour, few studies have investigated how individuals respond to ostracism by seeking solitude. Therefore, our study aims to explore the association between social ostracism and solitude seeking as well as the potential psychological mechanisms involved. We conducted three studies involving 488 Chinese students (59% female) and found that (a) long-term ostracism experiences positively correlated with preference for solitude, (b) short-term ostracism did not immediately lead to solitude seeking but increased the desire to establish new connections with others and (c) hostile assessment and negative emotions played a chain mediation role in the relationship between social ostracism and solitude seeking. These findings provide new insights and empirical evidence for understanding the relationship between social ostracism and solitude-seeking.

Understanding cellulose pyrolysis via ab initio deep learning potential field.

Comprehensive and dynamic studies of cellulose pyrolysis reaction mechanisms are crucial in designing experiments and processes with enhanced safety, efficiency, and sustainability. The details of the pyrolysis mechanism are not readily available from experiments but can be better described via molecular dynamics (MD) simulations. However, the large size of cellulose molecules challenges accurate ab initio MD simulations, while existing reactive force field parameters lack precision. In this work, precise ab initio deep learning potentials field (DPLF) are developed and applied in MD simulations to facilitate the study of cellulose pyrolysis mechanisms. The formation mechanism and production rate of both valuable and greenhouse products from cellulose at temperatures larger than 1073 K are comprehensively described. This study underscores the critical role of advanced simulation techniques, particularly DLPF, in achieving efficient and accurate understanding of cellulose pyrolysis mechanisms, thus promoting wider industrial applications.

Influence of Alcohol on Intracerebral Hemorrhage: From Oxidative Stress to Glial Cell Activation.

The intricate relationship between alcohol consumption and intracerebral hemorrhage (ICH) presents a nuanced field of study, especially concerning the dose-dependent impact on secondary brain injury (SBI). Recognizing the established risks associated with heavy drinking, this review delves deeper into the less understood territories of low to moderate alcohol consumption. By systematically analyzing recent studies, we uncover critical insights into how varying alcohol intake levels modulate ICH risk through mechanisms such as microglial activation, oxidative stress, and the protective potential of polyphenols. This analysis extends beyond the hypertensive effects of heavy alcohol use to explore the complex molecular pathophysiology involved in alcohol-related ICH. Our findings indicate that while heavy alcohol use unequivocally exacerbates ICH risk, moderate consumption and its associated polyphenols may offer neuroprotective effects against SBI, albeit within a finely balanced threshold. This review highlights the significant gaps in current understanding and underscores the urgent need for targeted research to elucidate these complex interactions. Through this comprehensive examination, we aim to inform more nuanced public health policies and intervention strategies, taking into account the diverse effects of alcohol consumption on ICH risk.

Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

BACKGROUND: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE: This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS: We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS: This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS: Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55662.

Ultrasonic liquid exfoliation for producing graphene materials from rice stem: Investigating cellular components and functionalities.

This study investigates a prospective and straightforward method for producing graphene material derived from biomass, examining the influence of plant cell composition and functions. The experimental outcomes highlight ultrasound's crucial role in synthesizing graphene material sourced from biomass. Ultrasound, a pivotal element in the experiment, significantly affects graphene production from biomass by working synergistically with the liquid components in the solvent system. Notably, the ethanol content reduces the solution's surface tension, facilitating the effective dispersion of biochar and graphene oxide sheets throughout the process. Simultaneously, the water content maintains the solution's polarity, enhancing the cavitation effect induced by ultrasound. Biomass-derived graphene is exfoliated utilizing an ultrasonic bath system (134.4 W, 40 kHz, 0.5 W/cm2) from biochar. The as-synthesized graphene oxide exhibits a structure comprising a few layers while remaining intact, featuring abundant functional groups. Interestingly, the resulting product displays nanopores with an approximate diameter of 100 nm. These nanopores are attributed to preserving specific cell structures, particularly those with specialized cell wall structures or secondary metabolite deposits from biomass resources. The study's findings shed light on the impact of cellular structure on synthesizing graphene material sourced from biomass, emphasizing the potential application of ultrasound as a promising approach in graphene production.

A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.

BACKGROUND: Emerging studies have reported the contribution of cholesterol to hepatocellular carcinoma (HCC) progression. However, the specific role and mechanism of cholesterol metabolism on spontaneous and progressive HCC development from the point of view of ferroptosis are still worth exploring. The present study aimed to reveal a novel mechanism of cholesterol metabolism-related ferroptosis in hepatocellular carcinoma cells. METHODS: Two microarray datasets (GSE25097, GSE22058) related to HCC were downloaded from Gene Expression Omnibus (GEO) datasets. Metabolomics analysis was performed by ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). The cholesterol-related proteins were downloaded from HMBD. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE25097 was used to identify ferroptosis-related genes, and GSE22058 was used to verify results. During these processes, chemical-protein interaction (CPI), protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Multivariate logistic regression analysis was used to test the associated pathway. RESULTS: We identified 8 differentially expressed ferroptosis-related genes (HAMP, PTGS2, IL1B, ALOX15B, CDKN2A, RRM2, NQO1 and KIF20A) and 4 differentially expressed cholesterol-related genes (LCAT, CH25H, CEL and CYP7A1). Furthermore, based on the predicted results with STITCH, we identified indomethacin and IL1B as the essential node for cholesterol-mediated ferroptosis in hepatocellular carcinoma cell. Multivariate logistic regression analysis showed the activities of plasma IL1B in liver cancer patients enrolled have been significantly affected by the level of plasma cholesterol (P < 0.001) and the test result of IL1B is a predictor variable causing the changes of serum Fe levels (P < 0.001). CONCLUSIONS: Our findings shed new light on the association between cholesterol metabolism and ferroptosis in HCC, and suggest that IL1B is the necessary node for cholesterol to lead to ferroptosis process in HCC. Also, we identified the potential role of indomethacin in adjuvant therapy of HCC with complications of abnormal cholesterol metabolism.

Strategies for utilizing covalent organic frameworks as host materials for the integration and delivery of bioactives.

Covalent organic frameworks (COFs), a new and developing class of porous framework materials, are considered a type of promising carrier for the integration and delivery of bioactives, which have diverse fascinating merits, such as a large specific surface area, designable and specific porosity, stable and orderly framework structure, and various active sites. However, owing to the significant differences among bioactives (including drugs, proteins, nucleic acid, and exosomes), such as size, structure, and physicochemical properties, the interaction between COFs and bioactives also varies. In this review, we firstly summarize three strategies for the construction of single or hybrid COF-based matrices for the delivery of cargos, including encapsulation, covalent binding, and coordination bonding. Besides, their smart response release behaviors are also categorized. Subsequently, the applications of cargo@COF biocomposites in biomedicine are comprehensively summarized, including tumor therapy, central nervous system (CNS) modulation, biomarker analysis, bioimaging, and anti-bacterial therapy. Finally, the challenges and opportunities in this field are briefly discussed.

Anti-Inflammatory Ergosteroid Derivatives from the Coral-Associated Fungi Penicillium oxalicum HL-44.

To obtain the optimal fermentation condition for more abundant secondary metabolites, Potato Dextrose Agar (PDA) medium was chosen for the scale-up fermentation of the fungus Penicillium oxalicum HL-44 associated with the soft coral Sinularia gaweli. The EtOAc extract of the fungi HL-44 was subjected to repeated column chromatography (CC) on silica gel and Sephadex LH-20 and semipreparative RP-HPLC to afford a new ergostane-type sterol ester (1) together with fifteen derivatives (2-16). Their structures were determined with spectroscopic analyses and comparisons with reported data. The anti-inflammatory activity of the tested isolates was assessed by evaluating the expression of pro-inflammatory factors Tnfα and Ifnb1 in Raw264.7 cells stimulated with LPS or DMXAA. Compounds 2, 9, and 14 exhibited significant inhibition of Ifnb1 expression, while compounds 2, 4, and 5 showed strong inhibition of Tnfα expression in LPS-stimulated cells. In DMXAA-stimulated cells, compounds 1, 5, and 7 effectively suppressed Ifnb1 expression, whereas compounds 7, 8, and 11 demonstrated the most potent inhibition of Tnfα expression. These findings suggest that the tested compounds may exert their anti-inflammatory effects by modulating the cGAS-STING pathway. This study provides valuable insight into the chemical diversity of ergosteroid derivatives and their potential as anti-inflammatory agents.

Ce/Mn/Cr: (Re,Y)3Al5O12 Phosphor Ceramics (Re = Gd, Tb and Lu) for White LED Lighting with Significant Spectral Redshift and Improved Color-Rendering Index.

In order to attain phosphor ceramics with a high Color-Rendering Index (CRI), samples with the composition of Y0.997-xRexCe0.003)3(Al0.9748 Mn2+0.024Cr3+0.0012)5O12(Rex = 0, Gd0.333, Gd0.666, Gd0.997, Tb0.333, Tb0.666, Tb0.997 and Lu0.997 were prepared by solid-state reaction and vacuum sintering, and exhibited potential for high-quality, solid-state lighting. Doping with Cr3+ and Mn2+ effectively enhanced the red component of Ce3+ spectra through the intense energy transfer from Ce3+ ions to Mn2+/Cr3+ ions. The crystal field splitting of [GdO8] and [TbO8] was more extensive than that of [YO8], causing a massive redshift in the Ce3+ emission peaks from 542 to 561 and 595 nm, while [LuO8] had an opposite effect and caused a blueshift with a peak position at 512 nm. White LED devices incorporating Ce/Mn/Cr: (Gd0.333Y0.664)3Al5O12 phosphor ceramic exhibited a high CRI of 83.97, highlighting the potential for enhancing the red-light component of white LED lighting.

RBC Transfusion Strategy in Oncological Patients with Chronic RBC Transfusion Therapy.

BACKGROUND: Red blood cell (RBC) transfusion therapy has greatly reduced mortality and morbidity in multiply transfused patients with oncological malignancies. The aim of this study was to underline the necessity of introducing a policy for extended RBC phenotyping of these patients and for the issuing of antigen-matched blood (at least for E antigen). METHODS: Multivariate logistic regression analysis was used to evaluate the associations of age, gender, transfusion history, and various malignancies with the development of red cell alloimmunization. RESULTS: Given the results of antibody identification, we finally obtained 732 cases to be analyzed, designating them as the p group. The respiratory system (231/732; 31.6%), digestive system (273/732; 37.3%), and female reproductive system (127/732; 17.3%) had the three highest alloimmunization rates in the p group. We screened 81 cases from the p group for which antibody screening in our laboratory had historically yielded negative results. Among the 81 cases with antibody seroconversion, anti-E was the most frequently observed antibody (37%). CONCLUSIONS: The results related to multivariate logistic regression analysis of the Rh group indicate that, in contrast to the other variates, transfusion confers a strongly increased risk of Rh blood system-related red cell alloimmunization. To reduce alloimmunization in tumor patients, it will be essential to introduce a policy for extended RBC phenotyping of high-risk patients and for the issuing of antigen-matched blood (at least for E antigen).

An eco-friendly ultrasound approach to extracting yellow dye from Cassia alata flower petals: Characterization, dyeing, and antibacterial properties.

Using natural dyes in dyeing industries becomes an alternative to synthetic dyes, which are known to contain harmful chemicals that can pose risks to the environment and human health. This study involves the extraction of yellow dye from Cassia alata flower petals, optimization of the extraction process using an ultrasonic bath (40 KHz and an input power of 500), ultrasonic probe (390 W, 455 W, 520 W, 585 W, and 650 W), and conventional heating (heating mantle with 30 °C, 40 °C, 50 °C, 60 °C, and 70 °C), characterization of the dye, as well as dyeing (cotton, silk, and leather) without using a mordant. The extracted yellow dye was further evaluated to determine its antibacterial activity against skin bacteria. Dye extraction optimization using UV-Visible spectrophotometric analysis revealed that the maximum yellow color in methanol extract (287 and 479 nm) was obtained at 50 °C for 45 min using ultrasonic water bath extraction, followed by the ultrasonic probe and direct heating. Based on the FTIR spectra, it is evident that OH is present at approximately 3300 cm-1, while CH stretches at around 2900 cm-1. A characteristic peak at 1608 cm-1 bears a striking similarity to anthraquinonoid-based compounds. Also, using the ultrasonic water bath dyeing technique at 50 °C for 45 min, the yellow color of cotton, silk, and leather was dyed optimally. Due to effective color removal after two washings with boiling soap liquid, the dyed cotton and silk fabric displayed good washing and rubbing fastness. Regarding antibacterial activity, the dye was highly active against all pathogens after extraction in methanol. The maximum inhibition was observed against Pseudomonas sp. with a MIC value of 1.56 mg/ml.

Microwave-induced hyperthermia in situ in the treatment of tumors of proximal humerus: long-term results with functionary sparing surgery.

BACKGROUND: The present study aimed to evaluate the indications, feasibility, clinical effectiveness and complications of the treatment with microwave in situ inactivation followed by curettage and bone grafting assisted with internal fixation, for the proximal humerus tumors. METHODS: The clinical data of 49 patients with primary or metastatic tumor of the proximal humerus who received intraoperative microwave inactivation in situ with curettage and bone grafting in our hospital from May 2008 to April 2021 were retrospectively analyzed. RESULTS: There were 25 males and 24 females, with an average age of 57.6 ± 19.9 years (range, 20-81). All patients were followed up for 7 to 146 months, with an average period of 69.2 ± 39.8 months. Up to the last follow-up, 14 patients died. The 5-year overall survival was 67.3%, and 5-year tumor-specific survival was 71.4%. The 5-year tumor-specific survival rates were 100% for aggressive benign tumors or low potential malignancy tumors, 70.1% for primary malignancies, and 36.9% for metastatic tumors. The average preoperative MSTS, constant-Murley and VAS scores were 16.81 ± 3.85, 62.71 ± 12.56 and 6.75 ± 2.47, which were all significantly improved at 6 weeks after operation and at the final follow-up (P < 0.05). CONCLUSIONS: Microwave inactivation in situ and curettage and bone grafting are a feasible treatment for tumors of proximal humeral, especially for malignant tumors and metastases, without the necessity of the replacement of the shoulder, with little trauma and good upper limb function, and with low local recurrence and distant metastasis.

Astragaloside IV promotes keratinocyte proliferation and migration through upregulating lncRNA H19 recruited ILF3 to enhance the stability of CDK4 mRNA.

Skin is the first line of the body to resist pathogen invasion. A potentially fatal infection may result from problems with wound healing. Small molecule drugs like astragaloside IV (AS-IV) show pro-healing activities, but the mechanisms are not fully understood. Using real-time quantitative PCR and a western blot assay, the amount of gene expression was evaluated. The proliferation and migration of keratinocytes were determined by MTS and wound healing assay, respectively. The binding of lncRNA H19 to RBP protein ILF3 and the binding of ILF3 protein to CDK4 mRNA were confirmed by RNA immunoprecipitation. Treatment with AS-IV enhanced the expression of lncRNA H19, ILF3, and CDK4 and improved the proliferation and migration of keratinocytes HaCaT. Additionally, apoptosis of keratinocytes was attenuated by AS-IV. Further studies showed that both lncRNA H19 and ILF3 were important for AS-IV-mediated keratinocyte growth and migration. In addition, lncRNA H19 recruited ILF3 to increase CDK4 mRNA level and enhanced cell proliferation. We discovered a lncRNA H19/ILF3/CDK4 axis that is activated by AS-IV to promote keratinocyte migration and proliferation. These results elucidate the mechanism of action of AS-IV and justify its application in further application in wound healing treatment.

Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

Artificial intelligence-quantified tumour-lymphocyte spatial interaction predicts disease-free survival in resected lung adenocarcinoma: A graph-based, multicentre study.

BACKGROUND AND OBJECTIVE: A high degree of lymphocyte infiltration is related to superior outcomes amongst patients with lung adenocarcinoma. Recent evidence indicates that the spatial interactions between tumours and lymphocytes also influence the anti-tumour immune responses, but the spatial analysis at the cellular level remains insufficient. METHODS: We proposed an artificial intelligence-quantified Tumour-Lymphocyte Spatial Interaction score (TLSI-score) by calculating the ratio between the number of spatial adjacent tumour-lymphocyte and the number of tumour cells based on topology cell graph constructed using H&E-stained whole-slide images. The association of TLSI-score with disease-free survival (DFS) was explored in 529 patients with lung adenocarcinoma across three independent cohorts (D1, 275; V1, 139; V2, 115). RESULTS: After adjusting for pTNM stage and other clinicopathologic risk factors, a higher TLSI-score was independently associated with longer DFS than a low TLSI-score in the three cohorts [D1, adjusted hazard ratio (HR), 0.674; 95% confidence interval (CI) 0.463-0.983; p = 0.040; V1, adjusted HR, 0.408; 95% CI 0.223-0.746; p = 0.004; V2, adjusted HR, 0.294; 95% CI 0.130-0.666; p = 0.003]. By integrating the TLSI-score with clinicopathologic risk factors, the integrated model (full model) improves the prediction of DFS in three independent cohorts (C-index, D1, 0.716 vs. 0.701; V1, 0.666 vs. 0.645; V2, 0.708 vs. 0.662) CONCLUSIONS: TLSI-score shows the second highest relative contribution to the prognostic prediction model, next to the pTNM stage. TLSI-score can assist in the characterising of tumour microenvironment and is expected to promote individualized treatment and follow-up decision-making in clinical practice.

Experimental animal models and evaluation techniques in intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is the most lethal type of cerebral stroke without effective therapy. Although clinical trials with various surgeries have been conducted, none have improved clinical outcomes compared to the current medical management for ICH. Several ICH animal models, including autologous blood injection, collagenase injection, thrombin injection, and microballoon inflation methods, have been developed to elucidate the underlying mechanisms of ICH-induced brain injury. These models could also be used for discovering new therapy for ICH preclinically. We summarize the existing ICH animal models and the evaluation parameters used to measure the disease outcomes. We conclude that these models, resembling the different aspects of ICH pathogenesis, have their advantages and disadvantages. None of the current models closely represent the severity of ICH seen in clinical settings. More appropriate models are needed to streamline ICH's clinical outcomes and be used for validating newly developed treatment protocols.

Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage.

During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH.

Searching by parts: Towards fine-grained image retrieval respecting species correlation.

Most of the existing works on fine-grained image categorization and retrieval focus on finding similar images from the same species and often give little importance to inter-species similarities. However, these similarities may carry species correlations such as the same ancestors or similar habits, which are helpful in taxonomy and understanding biological traits. In this paper, we devise a new fine-grained retrieval task that searches for similar instances from different species based on body parts. To this end, we propose a two-step strategy. In the first step, we search for visually similar parts to a query image using a deep convolutional neural network (CNN). To improve the quality of the retrieved candidates, structural cues are introduced into the CNN using a novel part-pooling layer, in which the receptive field of each part is adjusted automatically. In the second step, we re-rank the retrieved candidates to improve the species diversity. We achieve this by formulating a novel ranking function that balances between the similarity of the candidates to the queried parts, while decreasing the similarity to the query species. We provide experiments on the benchmark CUB200 dataset and Columbia Dogs dataset, and demonstrate clear benefits of our schemes.