Biomimetic nanomaterials in myocardial infarction treatment: Harnessing bionic strategies for advanced therapeutics.

Myocardial infarction (MI) and its associated poor prognosis pose significant risks to human health. Nanomaterials hold great potential for the treatment of MI due to their targeted and controlled release properties, particularly biomimetic nanomaterials. The utilization of biomimetic strategies based on extracellular vesicles (EVs) and cell membranes will serve as the guiding principle for the development of nanomaterial therapy in the future. In this review, we present an overview of research progress on various exosomes derived from mesenchymal stem cells, cardiomyocytes, or induced pluripotent stem cells in the context of myocardial infarction (MI) therapy. These exosomes, utilized as cell-free therapies, have demonstrated the ability to enhance the efficacy of reducing the size of the infarcted area and preventing ischaemic reperfusion through mechanisms such as oxidative stress reduction, polarization modulation, fibrosis inhibition, and angiogenesis promotion. Moreover, EVs can exert cardioprotective effects by encapsulating therapeutic agents and can be engineered to specifically target the infarcted myocardium. Furthermore, we discuss the use of cell membranes derived from erythrocytes, stem cells, immune cells and platelets to encapsulate nanomaterials. This approach allows the nanomaterials to camouflage themselves as endogenous substances targeting the region affected by MI, thereby minimizing toxicity and improving biocompatibility. In conclusion, biomimetic nano-delivery systems hold promise as a potentially beneficial technology for MI treatment. This review serves as a valuable reference for the application of biomimetic nanomaterials in MI therapy and aims to expedite the translation of NPs-based MI therapeutic strategies into practical clinical applications.

Assessment of Disrupted Brain Structural Connectome in Depressive Patients With Suicidal Ideation Using Generalized Q-Sampling MRI.

Suicide is one of the leading causes of mortality worldwide. Various factors could lead to suicidal ideation (SI), while depression is the predominant cause among all mental disorders. Studies have shown that alterations in brain structures and networks may be highly associated with suicidality. This study investigated both neurological structural variations and network alterations in depressed patients with suicidal ideation by using generalized q-sampling imaging (GQI) and Graph Theoretical Analysis (GTA). This study recruited 155 participants and divided them into three groups: 44 depressed patients with suicidal ideation (SI+; 20 males and 24 females with mean age = 42, SD = 12), 56 depressed patients without suicidal ideation (Depressed; 24 males and 32 females with mean age = 45, SD = 11) and 55 healthy controls (HC; nine males and 46 females with mean age = 39, SD = 11). Both the generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values were evaluated in a voxel-based statistical analysis by GQI. We analyzed different topological parameters in the graph theoretical analysis and the subnetwork interconnections in the Network-based Statistical (NBS) analysis. In the voxel-based statistical analysis, both the GFA and NQA values in the SI+ group were generally lower than those in the Depressed and HC groups in the corpus callosum and cingulate gyrus. Furthermore, we found that the SI+ group demonstrated higher global integration and lower local segregation among the three groups of participants. In the network-based statistical analysis, we discovered that the SI+ group had stronger connections of subnetworks in the frontal lobe than the HC group. We found significant structural differences in depressed patients with suicidal ideation compared to depressed patients without suicidal ideation and healthy controls and we also found several network alterations among these groups of participants, which indicated that white matter integrity and network alterations are associated with patients with depression as well as suicidal ideation.

Convolutional Neural Network-Based Deep Learning Model for Predicting Differential Suicidality in Depressive Patients Using Brain Generalized q-Sampling Imaging.

OBJECTIVE: Suicide is a priority health problem. Suicide assessment depends on imperfect clinician assessment with minimal ability to predict the risk of suicide. Machine learning/deep learning provides an opportunity to detect an individual at risk of suicide to a greater extent than clinician assessment. The present study aimed to use deep learning of structural magnetic resonance imaging (MRI) to create an algorithm for detecting suicidal ideation and suicidal attempts. METHODS: We recruited 4 groups comprising a total of 186 participants: 33 depressive patients with suicide attempt (SA), 41 depressive patients with suicidal ideation (SI), 54 depressive patients without suicidal thoughts (DP), and 58 healthy controls (HCs). The confirmation of depressive disorder, SA and SI was based on psychiatrists' diagnosis and Mini-International Neuropsychiatric Interview (MINI) interviews. In the generalized q-sampling imaging (GQI) dataset, indices of generalized fractional anisotropy (GFA), the isotropic value of the orientation distribution function (ISO), and normalized quantitative anisotropy (NQA) were separately trained in convolutional neural network (CNN)-based deep learning and DenseNet models. RESULTS: From the results of 5-fold cross-validation, the best accuracies of the CNN classifier for predicting SA, SI, and DP against HCs were 0.916, 0.792, and 0.589, respectively. In SA-ISO, DenseNet outperformed the simple CNNs with a best accuracy from 5-fold cross-validation of 0.937. In SA-NQA, the best accuracy was 0.915. CONCLUSIONS: The results showed that a deep learning method based on structural MRI can effectively detect individuals at different levels of suicide risk, from depression to suicidal ideation and attempted suicide. Further studies from different populations, larger sample sizes, and prospective follow-up studies are warranted to confirm the utility of deep learning methods for suicide prevention and intervention.

An Autoencoder and Machine Learning Model to Predict Suicidal Ideation with Brain Structural Imaging.

It is estimated that at least one million people die by suicide every year, showing the importance of suicide prevention and detection. In this study, an autoencoder and machine learning model was employed to predict people with suicidal ideation based on their structural brain imaging. The subjects in our generalized q-sampling imaging (GQI) dataset consisted of three groups: 41 depressive patients with suicidal ideation (SI), 54 depressive patients without suicidal thoughts (NS), and 58 healthy controls (HC). In the GQI dataset, indices of generalized fractional anisotropy (GFA), isotropic values of the orientation distribution function (ISO), and normalized quantitative anisotropy (NQA) were separately trained in different machine learning models. A convolutional neural network (CNN)-based autoencoder model, the supervised machine learning algorithm extreme gradient boosting (XGB), and logistic regression (LR) were used to discriminate SI subjects from NS and HC subjects. After five-fold cross validation, separate data were tested to obtain the accuracy, sensitivity, specificity, and area under the curve of each result. Our results showed that the best pattern of structure across multiple brain locations can classify suicidal ideates from NS and HC with a prediction accuracy of 85%, a specificity of 100% and a sensitivity of 75%. The algorithms developed here might provide an objective tool to help identify suicidal ideation risk among depressed patients alongside clinical assessment.

The immunomodulatory peptide bursopentin (BP5) enhances proliferation and induces sIgM expression in DT40 cells.

BACKGROUND: In the recent past, many studies have been focused on extracts of BF and multiple biologically active factors and their effects on humoral immune system in chickens and birds. However, the mechanism of those immunomodulatory peptides on the B lineage cells proliferation and antibody production in chicken is fairly unknown. DT40 cell line, an avian leucosis virus-induced chicken pre-B cell line, expresses immunoglobulin M (IgM) isotype B cell reporter in the plasma membrane. There are many evidences suggesting that DT40 cells are best characterized as a bursal stem cell line. Because of the unique characteristics of DT40 cell line, it has been widely used to observe biological processes of pre-B lymphocyte cell within living cells. METHODS: The chicken B cell line DT40 was cultured in Roswell Park Memorial Institute (RPMI) 1640 medium and cytotoxicity was studied. Also, effect of BP5 on cell proliferation and cell cycle distribution of DT40 cells was studied. Also, the effect of BP5 on sIgM mRNA expression was studied by using real-time PCR. OBJECTIVES: To investigat the effects of Bursopentin (Cys-Lys-Arg-Val-Tyr, BP5) on a chicken promyelocyte cell line DT40, assays of cell proliferation, cell cycle distribution, detection of surface immunoglobulin G (sIgM) mRNA expression and gene microarray analysis were performed. RESULTS: The results showed that BP5 displayed concentration-dependent effects on the proliferation, cell cycle, and sIgM mRNA expression in DT40 cells. And the analysis of expression profiles identified a signature set of 3022 genes (1254 up regulated genes, 1762 down regulated genes), which clearly discriminated the BP5-treated DT40 cells from control with high certainty (P≤0.02). The results of microarray analysis were confirmed by quantitative reverse transcription-polymerase chain reaction for 12 of the differentially expressed genes. CONCLUSION: Theses findings showed the immuno-activity effect of BP5 on B lymphocyte and indicated that BP5 treatment regulated eight signaling pathways, in which Toll-like signaling pathway was the most significant enrichment pathway.

Discovery of a novel ROCK2 inhibitor with anti-migration effects via docking and high-content drug screening.

Rho-associated protein kinase (ROCK) mediated the reorganization of the actin cytoskeleton and has been implicated in the spread and metastatic process of cancer. In this study, structure-based high-throughput virtual screening was used to identify candidate compounds targeting ROCK2 from a chemical library. Moreover, high-content screening based on neurite outgrowth of SH-SY5Y cells (a human neuroblastoma cell line) was used for accelerating the identification of compounds with characteristics of ROCK2 inhibitors. The effects of bioactive ROCK2 inhibitor candidates were further validated using other bioassays including cell migration and wound healing in SH-SY5Y cells. Through the combined virtual and high-content drug screening, the compound 1,3-benzodioxol-5-yl[1-(5-isoquinolinylmethyl)-3-piperidinyl]-methanone (BIPM) was identified as a novel and potent ROCK2 inhibitor. Exposure of SH-SY5Y cells to BIPM led to significant changes in neurite length, cell migration and actin stress fibers. Further experiments demonstrated that BIPM was able to significantly inhibit phosphorylation of cofilin, a regulatory protein of actin cytoskeleton. These results suggest that BIPM could be considered as a promising scaffold for the further development of ROCK2 inhibitors for anti-cancer metastasis.

Long-term postoperative outcomes of bilateral lateral rectus recession vs unilateral recession-resection for intermittent exotropia.

AIM: To discuss the long-term postoperative results of bilateral lateral rectus recession (BLR) and unilateral lateral rectus recession-medial rectus resection (RR) in therapy of intermittent exotropia. METHODS: We retrospectively analyzed 213 cases of intermittent exotropia who underwent surgery between 2008 and 2010. The patients were grouped into BLR group and RR group. Motor outcomes were divided into three groups on the basis of the angle of deviation after surgery: overcorrection (esotropia/phoria >5(Δ)), orthophoria (esotropia/phoria ≤5(Δ) to exotropia/phoria ≤10(Δ)), and undercorrection/recurrence (exotropia/phoria >10(Δ)). Titmus test was used to evaluate stereoacuity, the stereoacuity <800s of arc meaned the patients had stereopsis. Surgical outcome including motor criteria and sensory status were compared at postoperative 6, 12, 24mo and at 36mo examination between groups. RESULTS: At 12, 24mo after surgery, the motor outcomes had no difference (P>0.05) between groups. However, the motor outcomes at 6, 36mo were signally different in each group, indicating the success rate in RR group at 6mo was higher than that in BLR group (83.02% vs 82.24%, P<0.05) but the result was contrary at the 3y examination (60.75% vs 43.40%, P<0.05). No statistical significance were found in the sensory outcomes between the groups at mean of 3.7y follow-up. CONCLUSION: The motor outcomes in RR group were better than in BLR group at 6mo after surgery, while the 3y outcomes were better in BLR group. This may be due to the recurrence rate of the BLR was lower than the RR group's.

Gastroenteritis outbreaks caused by Norovirus genotype II.7 in a college in China (Zhuhai, Guangdong) in 2011.

BACKGROUND: Noroviruses are the most common cause of epidemic gastroenteritis worldwide. Noroviruses are comprised of at least five genogroups (GI-GV) and >35 genotypes. GII.7 is a nonpredominant genotype associated with Norovirus outbreaks. On November 17, 2011, Zhuhai Center for Disease Control monitored an increasing number of gastroenteritis cases at a local college. To determine the causes and control the outbreak effectively, we carried out an epidemiologic investigation. METHODS: Suspected cases were defined as those with one of the following symptoms: nausea, vomiting, abdominal pain, or diarrhea presenting on or after November 15 among the people who lived at the college. Probable cases were defined as cases with vomiting or diarrhea over three times per day on or after November 15. Confirmed cases were suspected or probable cases positive for Norovirus (nucleic acid). We conducted a case-control study to identify risk factors of the outbreak. Norovirus was tested by real-time reverse transcription-polymerase chain reaction, and Norovirus polymerase chain reaction products were further sequenced. RESULTS: In total, 63 cases were identified, which were scattered in all 14 departments of the college. The outbreak lasted for 84 h. Time distribution mode indicated a point-source outbreak. Fifty-one cases and 94 controls were contacted. Seventy-five percent of the cases compared to 19% of the controls were exposed to delicatessens (various salad and meat products) from the "Y" convenience store (odds ratio=12, 95% confidence interval 5.4-28). Laboratory tests showed 14 of the 15 cases and two asymptomatic food handlers were positive for Norovirus nucleic acid. There was 100% similarity between the cases and the food handlers when we compared the nucleotide sequences of Norovirus, which clustered with GII.7 genotype. CONCLUSIONS: Delicatessens from the "Y" convenience store were associated with the GII.7 Norovirus outbreak. We strongly recommend food supervision and quality control in convenience stores to decrease the risk of future Norovirus outbreaks.

[The current epidemic situation and surveillance regarding hemorrhagic fever with renal syndrome in China, 2010].

OBJECTIVE: To analyze the surveillance data on hemorrhagic fever with renal syndrome (HFRS) including the epidemiological characteristics and trend of the disease, in 2010. METHODS: Descriptive methods were conducted to analyze the surveillance data in 2010 which were collected from the internet-based National Notifiable Disease Reporting System and 40 HFRS sentinels in China. RESULTS: There were 9526 cases of HFRS reported in 2010 in the country with an annual morbidity of 0.71/10(5), which was higher than that reported in 2009. And the case fatality rate in 2010 was 1.24%. During the year 2010, most cases were reported in spring and autumn-winter season, with November as the peak month. The proportion of cases reported in autumn-winter season was higher than that in spring. The number of cases reported in males was higher than that in females among all the age groups, and similar pattern of mortality could be seen in most of the age groups. The percentage of cases over 60 years old had increased in recent years. Farmers were still under the highest risk. Density and the virus-carrying rate of animal hosts, as well as the infection rate were relatively stable and similar to the previous findings. As to the prevailing species, Apodemus agrarius and Rattus norvegicus were still the most common and leading animal hosts. However, the dominant species in sentinel of Yunnan were Rattus flavipectus and Eothenomys miletus respectively, and a new hantavirus called LUXV was found, namely Eothenomys miletus. CONCLUSION: HFRS cases were widely distributed in most provinces of China, but cases mainly focus on certain areas and present the nature of aggregation. The risk of outbreak could not be ruled out for variety of factors. Population characteristics and seasonal fluctuation had been changing.