A series of liquid crystalline/crystalline block copolymers (BCPs) containing poly(methacrylate) block with liquid crystalline (LC) azobenzene moieties in the side chains (PMMAzo) and crystalline ...block poly(l-lactide) (PLLA) were prepared. The interplay of microphase separation, crystallization and LC ordering in these BCPs was investigated. It is revealed that microphase separation between two blocks is favorable to the LC ordering, which is attributed to the enhanced local concentration of LC moieties in PMMAzo microdomains. For a similar reason, crystallization of PLLA can intensify microphase separation thus facilitate LC ordering of PMMAzo. PLLA crystallization may also stabilize the LC structure, leading to phase transition temperatures of the BCPs higher than that of PMMAzo homopolymer. On the other hand, the LC ordering can conversely affect crystallization of PLLA. The crystallizability of PLLA is weakened by the chemically linked PMMAzo block. The special PLLA ε-crystals, which are usually formed in the presence of organic solvents, are unexpectedly observed under suitable conditions.
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•A series of crystalline/liquid crystalline block copolymers (PMMAzo-b-PLLA) with well-defined structure were synthesized.•The interplay of microphase separation, crystallization and LC ordering in these crystalline/LC BCPs were investigated.•PLLA crystallization can stabilize the liquid crystalline structure, leading to an enhanced LC ordering.•Under suitable conditions, the LC ordering can induce formation of PLLA ε-crystals in the bulk.
Fatty liver is a high incidence of perinatal disease in dairy cows caused by negative energy balance, which seriously threatens the postpartum health and milk production. It has been reported that ...lysine acetylation plays an important role in substance and energy metabolism. Predictably, most metabolic processes in the liver, as a vital metabolic organ, are subjected to acetylation. Comparative acetylome study were used to quantify the hepatic tissues from the severe fatty liver group and normal group. Combined with bioinformatics analysis, this study provides new insights for the role of acetylation modification in fatty liver disease of dairy cows.
We identified 1841 differential acetylation sites on 665 proteins. Among of them, 1072 sites on 393 proteins were quantified. Functional enrichment analysis shows that higher acetylated proteins are significantly enriched in energy metabolic pathways, while lower acetylated proteins are significantly enriched in pathways related to immune response, such as drug metabolism and cancer. Among significantly acetylated proteins, many mitochondrial proteins were identified to be interacting with multiple proteins and involving in lipid metabolism. Furthermore, this study identified potential important proteins, such as HADHA, ACAT1, and EHHADH, which may be important regulatory factors through modification of acetylation in the development of fatty liver disease in dairy cows and possible therapeutic targets for NAFLD in human beings.
This study provided a comprehensive acetylome profile of fatty liver of dairy cows, and revealed important biological pathways associated with protein acetylation occurred in mitochondria, which were involved in the regulation of the pathogenesis of fatty liver disease. Furthermore, potential important proteins, such as HADHA, ACAT1, EHHADH, were predicted to be essential regulators during the pathogenesis of fatty liver disease. The work would contribute to the understanding the pathogenesis of NAFLD, and inspire in the development of new therapeutic strategies for NAFLD.
Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs.
Nine ...hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed.
Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%-7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission.
The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).
A facile and efficient approach for the synthesis of a variety of acridines via the tandem coupling/cyclization of substituted 2-bromobenzaldehydes and anilines is described. The reaction can be ...accomplished with ease in the presence of a catalytic amount of Pd2(dba)3 and diphosphine ligand dppf, providing a broad range of substituted acridines in good to excellent yields (up to 99%). The Lewis acid, AlCl3, is required to promote the cyclization for less electron-rich anilines.
In the present work, the nucleation mechanism for crystallization of poly(ε-caprolactone)s grafted on multi-walled carbon nanotubes (MWCNTs-g-PCLs), in which the PCL chains are structurally confined, ...was studied using self-nucleation method and the effects of the molecular weight and grafting density were investigated. It is found that the structural confinement reduces the nucleation activity of the self-nuclei but enhances the interaction between MWCNTs and PCL chains, leading to a narrower self-nucleation domain (DII) or even disappearance of DII. The PCL chains are more stretched at a larger grafting density and higher molecular weight of PCL, which facilitates formation of self-nuclei but also increases the nucleation activity of MWCNTs. The nucleation activity of MWCNTs may be enhanced at a higher grafting density as well. The values of nucleation efficiency of MWCNTs in the blend and MWCNTs-g-PCLs were also evaluated. Higher nucleation efficiency is observed for the MWCNTs-g-PCL with shorter PCL chains but higher grafting density.
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Abstract
Background
The vital signs of trauma patients are complex and changeable, and the prediction of blood transfusion demand mainly depends on doctors’ experience and trauma scoring system; ...therefore, it cannot be accurately predicted. In this study, a machine learning decision tree algorithm classification and regression tree (CRT) and eXtreme gradient boosting (XGBoost) was proposed for the demand prediction of traumatic blood transfusion to provide technical support for doctors.
Methods
A total of 1371 trauma patients who were diverted to the Emergency Department of the First Medical Center of Chinese PLA General Hospital from January 2014 to January 2018 were collected from an emergency trauma database. The vital signs, laboratory examination parameters and blood transfusion volume were used as variables, and the non-invasive parameters and all (non-invasive + invasive) parameters were used to construct an intelligent prediction model for red blood cell (RBC) demand by logistic regression (LR), CRT and XGBoost. The prediction accuracy of the model was compared with the area under the curve (AUC).
Results
For non-invasive parameters, the LR method was the best, with an AUC of 0.72 95% confidence interval (CI) 0.657–0.775, which was higher than the CRT (AUC 0.69, 95% CI 0.633–0.751) and the XGBoost (AUC 0.71, 95% CI 0.654–0.756,
P
< 0.05). The trauma location and shock index are important prediction parameters. For all the prediction parameters, XGBoost was the best, with an AUC of 0.94 (95% CI 0.893–0.981), which was higher than the LR (AUC 0.80, 95% CI 0.744–0.850) and the CRT (AUC 0.82, 95% CI 0.779–0.853,
P
< 0.05). Haematocrit (Hct) is an important prediction parameter.
Conclusions
The classification performance of the intelligent prediction model of red blood cell transfusion in trauma patients constructed by the decision tree algorithm is not inferior to that of the traditional LR method. It can be used as a technical support to assist doctors to make rapid and accurate blood transfusion decisions in emergency rescue environment, so as to improve the success rate of patient treatment.
Oncolytic herpes simplex viruses (oHSVs) have been approved for clinical usage and become more and more popular for tumor virotherapy. However, there are still many issues for the oHSVs used in ...clinics and clinical trials. The main issues are the limited anti-tumor effects, intratumor injection, and some side effects. To overcome such challenges, here we review the genetic engineering of the envelope glycoproteins for oHSVs to target tumors specifically, and at the same time we summarize the many neutralization antibodies against the envelope glycoproteins and align the neutralization epitopes with functional domains of the respective glycoproteins for future identification of new functions of the glycoproteins and future engineering of the epitopes to escape from host neutralization.
The Danxia geoheritage has emerged as a compelling subject of study, while the Tethys-Himalayan tectonic domain continues to captivate scholarly attention. However, a noteworthy gap exists in the ...literature concerning the intricate relationship between Danxia formation and the evolution of regional tectonics. In this study, we conducted a comprehensive analysis involving structure interpretation and terrain assessment, utilizing Landsat8 imagery and ASTER Global Digital Elevation Model. Additionally, field investigations were carried out on 35 Danxia landforms in the southern Sichuan Basin. Our findings revealed four distinct types of Danxia heritages—cliff (32 sites), peak (7 sites), cave (5 sites), and valley (6 sites)—with a predominant presence on slopes exceeding 40°. Moreover, valley-type sites exhibited a propensity for development at altitudes surpassing 400 m. The observed formations were intricately linked to Late Jurassic to Cretaceous red beds, influenced by the synergistic effects of the southward thrusting of the Qinling Orogen and the northwestward expansion of the Jiangnan Orogen. The control exerted by Cenozoic faults, folds, and joints—resulting from the eastward expansion of the Tibetan Plateau and the southeastward extrusion of the Chuandian terrane—further shaped these Danxia landscapes. Notably, the eastward expansion of the Tibetan Plateau induced the Cenozoic uplift of the southern Sichuan Basin, initiating a rapid denudation process of red beds crucial to the formation of Danxia landforms. Consequently, the Tethys-Himalayan tectonic evolution not only provided the material and structural foundations for these formations but also exerted a profound influence on their development in the southern Sichuan Basin. This study significantly contributes to our enhanced understanding of the spatial distribution of Danxia landforms in China.
Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR ...antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa.
Alzheimer's disease (AD) is a common neurodegenerative disease that tends to occur in the elderly. The main symptom is hypomnesia. More and more older people are suffering from this disease ...worldwide. By 2050, 152 million people worldwide are expected to have AD. It is thought that the aggregation of amyloid-beta peptides and hyper-phosphorylated tau tangles contribute to AD. The microbiota-gut-brain (MGB) axis appears as a new concept. The MGB axis is a collection of microbial molecules produced in the gastrointestinal tract that influence the physiological function of the brain. In this review, we discuss how the gut microbiota (GM) and its metabolites affect AD in different ways. Dysregulation of the GM has been shown to be involved in various mechanisms involved in memory and learning functions. We review the current literature on the role of the entero-brain axis in the pathogenesis of AD and its potential role as a future therapeutic target in the treatment and/or prevention of AD.
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